ORCID Profile
0000-0001-7347-9989
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Flinders Medical Centre
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Flinders University
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Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1111/JTH.12955
Abstract: Recommendations for management of cancer-related venous thromboembolism (VTE) in patients already receiving anticoagulant therapy are based on low-quality evidence. This international registry sought to provide more information on outcomes after a breakthrough VTE in relation to anticoagulation strategies. Patients with cancer and VTE despite anticoagulant therapy were reported to the registry. Data on treatments, VTE events, major bleeding, residual thrombosis symptoms and death were collected for the following 3 months. Breakthrough VTE and subsequent recurrences were objectively verified. Outcomes with different treatment strategies were compared with Cox proportional hazards regression. We registered 212 patients with breakthrough VTE. Of those, 59% had adenocarcinoma and 73% had known metastases. At the time of the breakthrough event, 70% were on low-molecular-weight heparin (LMWH) and 27% on a vitamin K antagonist (VKA) 70% had a therapeutic or supratherapeutic dose. After breakthrough the regimen was: unchanged therapeutic dose in 33%, dose increased in 31%, switched to another drug in 24% and other management in 11%. During the following 3 months 11% had another VTE, 8% had major bleeding and 27% died. Of the survivors, 74% had residual thrombosis symptoms. Additional VTE recurrence was less common with LMWH than with a VKA (hazard ratio [HR], 0.28 95% confidence interval [CI], 0.11-0.70) but similar with unchanged or increased anticoagulant intensity (HR, 1.09 95% CI, 0.45-2.63). The bleeding rate did not increase significantly with dose escalation. Morbidity and mortality are high after recurrence of cancer-related VTE despite anticoagulation. Further treatment appears to be more effective with LMWH than with a VKA.
Publisher: Wiley
Date: 1980
Abstract: In this study of 18 cancer patients, results of laboratory evaluation of a "hypercoagulable state" have been correlated with the extent of the disease and the functional activity of the patients. Most coagulation tests were normal. Higher levels of serum fibrinogen degradation products were associated with wider dissemination of disease. Fibrinogen survival time (t1/2) was shorter in patients with extensive disease than in those with less extensive disease (P < 0.05) platelet t1/2 was also shorter in the former group, though not significantly. Coexistence of severest physical disability and extensive disease was associated with the most marked reduction of platelet and fibrinogen t1/2. There was little correlation between platelet and fibrinogen t1/2, thus suggesting independent mechanisms of destruction of the two blood components. We suggest that future studies of hemostatic changes in cancer patients should include assessment of impairment of physical performance of the patients, as well as the extent of the tumor.
Publisher: AMPCo
Date: 09-1979
DOI: 10.5694/J.1326-5377.1979.TB125717.X
Abstract: The management of patients who require surgery while being treated with oral anticoagulants is a difficult balance between the risks of bleeding and those of recurrent thromboembolism. The urgency and the extent and site of surgery are important considerations, as are the strength of the indication for anticoagulants and the degree of anticoagulation. A practical approach is outlined for various situations that may be encountered.
Publisher: Georg Thieme Verlag KG
Date: 15-10-2008
Abstract: Of the various prophylactic agents evaluated, four have been found to be effective. These are oral anticoagulants, low-dose heparin, mechanical devices which increase venous blood-flow in the leg, and Dextran. Oral anticoagulants have been shown to be effective in patients having abdominal, thoracic, or hip surgery, when treatment was started either before surgery or in the immediate postoperative period. They have also been shown to be effective in medical patients. The evidence derives from studies which showed that treatment can reduce total mortality, prevents venous thromboembolism detected clinically or at autopsy, and prevents thrombosis diagnosed with venography. On the other hand, the incidence of thrombosis diagnosed by 125I-fibrinogen scanning was not reduced when oral anticoagulants were started just before or just after surgery. This suggests that oral anticoagulant treatment starting in the immediate postoperative period may not prevent formation of the initial thrombotic nidus, but is clinically effective because it prevents extension of the nidus to form a significant thrombus. Bleeding has been a significant complication in almost all studies of surgical patients, and this is the major factor which has prevented widespread use of oral anticoagulant prophylaxis. In addition, the need for careful laboratory monitoring makes this approach inconvenient and adds to its expense. Low-dose heparin has been shown to be effective in general surgical and medical patients, but results have been inconclusive in patients having elective hip surgery, and this approach is probably ineffective in patients with hip fracture. In general surgical patients, low-dose heparin prophylaxis has been shown to prevent pulmonary embolism diagnosed at autopsy examination or with lung scanning, and calf and thigh vein thrombosis diagnosed with 125I-fibrinogen leg-scanning. A slight, but statistically significant, increase in the frequency of wound hematoma and a greater postoperative hematocrit fall have been reported when heparin was given three times daily, but not with the twice daily heparin injection regimen. In these studies, low-dose heparin was given without laboratory control of its anticoagulant effect, so that this prophylactic approach is simple, but the need for subcutaneous injections is a disadvantage of this approach. Results with methods which increase venous blood-flow in the leg have varied, depending on the technic used. Active measures, such as intermittent pneumatic calf compression or peroperative electrical calf muscle stimulation, have been shown to prevent thrombosis detected with 125I-fibrinogen leg-scanning. However, while the evidence suggests that both methods are effective in relatively low risk patients, they may have limited value in the high risk patient who is confined to bed for a long time. These methods are free of side effects and relatively inexpensive, but intermittent calf compression, in particular, is slightly cumbersome...
Publisher: Georg Thieme Verlag KG
Date: 15-10-2008
Abstract: Numerous factors that influence cell-surface carbohydrate composition remain to be elucidated. The combination of novel biochemical and metabolism-based approaches with emerging genomic methods promises to accelerate efforts to understand glycosylation.
Publisher: Georg Thieme Verlag KG
Date: 2016
DOI: 10.1160/TH15-09-0752
Abstract: Risks of recurrence and bleeding are highest during the first weeks of anticoagulant therapy for venous thromboembolism (VTE). We therefore examined the early time course of recurrence and major bleeding in a pre-specified sub-analysis of the AMPLIFY trial, a randomised, double-blind, six-month comparison of oral apixaban with conventional therapy (enoxaparin followed by warfarin) in 5,395 patients with symptomatic proximal deep-vein thrombosis or pulmonary embolism. Early events were of particular interest because apixaban was given without initial heparin treatment. The primary efficacy and safety outcomes were the incidences of the adjudicated composite of recurrent symptomatic VTE or death related to VTE, and of adjudicated major bleeding, respectively. This analysis reports on recurrence and bleeding after 7, 21, and 90 days of therapy, in addition to the previously reported end-of-study results. These were the times specified before statistical analysis. Recurrent VTE after 7, 21, and 90 days, and six months had occurred in 18 (0.7%), 29 (1.1%), 46 (1.8%), and 59 patients (2.3%), respectively, given apixaban, and in 23 (0.9%), 35 (1.3%), 58 (2.2%), and 71 patients (2.7%), respectively, given conventional therapy. Major bleeding had occurred during these time intervals in 3 (0.1%), 5 (0.2%), 11 (0.4%), and 15 patients (0.6%), respectively, who received apixaban, and in 16 (0.6%), 26 (1.0%), 38 (1.4%), and 49 patients (1.8%), respectively, given conventional therapy. Efficacy of apixaban was non-inferior at each time point, with no excess of early recurrences. The reduced bleeding risk associated with apixaban began early during the course of treatment.
Publisher: Therapeutic Guidelines Limited
Date: 08-2001
Publisher: Wiley
Date: 2003
DOI: 10.1592/PHCO.23.1.109.31913
Abstract: A 74-year-old man who was receiving warfarin for atrial fibrillation experienced an abrupt increase in his international normalized ratio (INR) after taking acetaminophen. To investigate this effect, the patient's anticoagulation therapy was stabilized, and he was given acetaminophen 1 g 4 times/day for 3 days. His INR rose from 2.3 before receiving acetaminophen to 6.4 on the day after acetaminophen was discontinued. Warfarin was stopped for 2 days, and the patient's INR returned to 2.0. Warfarin was restarted at the same dosage, and his INR remained within 2.0-3.0 for 6 months. Factor VII activity decreased from 29.4% before acetaminophen therapy to 15.5% when his INR was 6.4, and factor X activity fell from 27.0% to 20.2%. His warfarin plasma concentration was 1.54 microg/ml before acetaminophen compared with 1.34 microg/ml when his INR was 6.4. No significant changes in drug intake, clinical status, diet, or lifestyle were noted. Changes in INR of this magnitude with the addition of another drug during stable anticoagulation therapy suggest a drug interaction. The lack of an increase in warfarin plasma concentration associated with the increased INR suggests a possible pharmacodynamic mechanism for this interaction. Acetaminophen or a metabolite may enhance the effect of oral coumarin anticoagulants by augmenting vitamin K antagonism. Thus, the anticoagulant effect of warfarin may be significantly elevated after only a few days of acetaminophen therapy. Patients receiving warfarin should be counseled to have their INR monitored more frequently when starting acetaminophen at dosages exceeding 2 g/day.
Publisher: Massachusetts Medical Society
Date: 23-12-2010
Publisher: Oxford University Press (OUP)
Date: 24-10-2008
Publisher: Elsevier BV
Date: 05-1987
DOI: 10.1016/0049-3848(87)90155-1
Abstract: The influence of antithrombin III (ATIII) level and ATIII activity, measured during intravenous heparin treatment for venous thromboembolism (VTE), on 'heparin requirement' (the heparin dose required to prolong the activated partial thromboplastin time (APTT) into its designated therapeutic range), and on the likelihood of recurrent VTE during the first month of anticoagulant therapy, were examined in a prospective study of 232 patients with VTE treated according to a standard protocol. 15 patients with recurrent VTE (6.5%) had a lower mean APTT during heparin treatment than patients without recurrence a finding due partly to their heparin requirement. However, there was no measurable relationship between ATIII level or ATIII activity and either heparin requirement or recurrence of VTE. By contrast, both the presence of disseminated malignancy and the development of heparin induced thrombocytopenia were powerful, clinically recognisable, risk factors for recurrence during or soon after heparin therapy.
Publisher: AMPCo
Date: 08-2001
Publisher: Georg Thieme Verlag KG
Date: 2009
DOI: 10.1160/TH08-09-0563
Abstract: In the initial treatment of venous thromboembolism (VTE) fondaparinux, a pentasaccharide, is a good alternative to heparin. Whether this is also true for cancer patients is unknown. We performed two post-hoc analyses of two randomized studies to compare efficacy, safety and overall survival of fondaparinux to standard initial (low-molecular-weight) heparin (LMWH) treatment in cancer patients with venous thromboembolism. Two hundred thirty-seven cancer patients with deep venous thrombosis (DVT) were initially treated with fondaparinux or enoxaparin. Two hundred forty cancer patients with pulmonary embolism (PE) received fondaparinux or unfractionated heparin. The initial treatment was followed by vitamin K antagonists. In DVT patients, the three-month recurrence rate was 5.4% in the enoxaparin recipients compared to 12.7% in those treated with fondaparinux [absolute difference 7.3%, 95% CI 0.1, 14.5]. A recurrence was observed in 8.9% of the PE patients treated with fondaparinux compared to 17.2% in the unfractionated heparin recipients [absolute difference –8.3, 95% CI –16.7, 0.1]. In both studies no difference in bleeding and overall survival was observed. Regarding overall survival and bleeding fondaparinux is comparable to enoxaparin and unfractionated heparin in cancer patients. No significant differences in recurrent VTE were observed when comparing fondaparinux with unfractionated or LMWH. Because of study limitations these results should be considered hypothesis-generating.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2002
DOI: 10.1097/00063198-200209000-00005
Abstract: Debate continues about whether and to what extent travel predisposes to venous thrombosis and pulmonary embolism (PE). Almost certainly, the strength of any association was greatly exaggerated in recent press reports. Conclusions from case-control studies vary, with some finding no excess of recent travel among patients with venous thromboembolism and others reporting a two-four fold excess. The strongest evidence that prolonged air travel predisposes to thrombosis comes from the travel history of people who present with PE immediately after landing. Two independent analyses suggest that the risk of early embolism increases exponentially with travel times beyond 6 hours and may reach 1:200,000 passengers traveling for more than 12 hours. The most likely explanation is venous stasis in the legs from prolonged sitting, and there is evidence (preliminary and controversial) that elastic support stockings may prevent deep vein thrombosis in people who travel long-distances. There is an urgent need for more and better studies to define the absolute hazard from travel-related thrombosis and the personal risk factors that may contribute. Without these, it is difficult to give a balanced account to people who intend to travel or to consider definitive prevention trials. Case reports suggest that in most cases, travel-related thrombosis has affected people who were also at risk because of previous thrombosis, recent injury, or other predispositions. This makes it sensible to target such "at risk" people with advice about hazards and precautions, at least until formal study validates some other approach.
Publisher: Springer Science and Business Media LLC
Date: 1980
DOI: 10.1007/BF00558448
Publisher: Elsevier BV
Date: 12-1986
DOI: 10.1016/S0140-6736(86)91431-5
Abstract: Two anticoagulant regimens, similar except for the timing of warfarin therapy, were compared in patients with clinically submassive venous thromboembolism (VTE). Warfarin was begun after 7 days of continuous intravenous heparin infusion in group L (127 patients) or within 3 days (average 1 day) of starting heparin in group S (139 patients), with similar outcomes. The frequency of symptomatic VTE recurrence during the hospital stay was 4.7% in group L and 3.6% in group S, and that of symptomless new perfusion defects 8.5% in group L and 3.9% in group S. On routine iodine-125-fibrinogen leg scanning of patients presenting with distal thrombosis (in the calf, popliteal, or distal femoral veins) 3.6% of group S but no group L patients had symptomless proximal extension. The incidence of bleeding was similar with both regimens. Outpatient follow-up showed no excess recurrent VTE in either treatment group. Early warfarin treatment significantly shortened hospital stay by an average of 3.9 days (30%) in patients admitted solely because of VTE.
Publisher: American Society of Hematology
Date: 11-1970
DOI: 10.1182/BLOOD.V36.5.623.623
Abstract: The safest and most practical method of administering long-term anticoagulants in pregnancy is uncertain because treatment of the mother with vitamin K antagonists may be complicated by hemorrhage in the fetus. The effects on the fetus of giving coumadin in pregnancy was evaluated in rabbits. When coumadin was given from early pregnancy until term, all of the fetuses were stillborn with widespread hemorrhages. However, the fetuses were born alive and without hemorrhage when (1) coumadin was stopped 4-5 days before delivery, at which time the level of coagulation factors had almost returned to normal and (2) when delivery was performed by cesarean section at a time when the fetal coagulation defect was severe. It is suggested that the risk of fetal hemorrhage is high only when fetuses with a severe coagulation defect are exposed to the trauma of delivery.
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.TMRV.2015.11.002
Abstract: Although red blood cell transfusion is a potentially lifesaving intervention in severely anemic and acutely bleeding patients, some observational studies have suggested that prolonged red cell storage before transfusion is associated with harm. INFORM is a large, pragmatic, randomized controlled trial comparing the effect of the shorter storage with longer storage red blood cell transfusions on inhospital mortality in hospitalized patients who require a blood transfusion. The trial is being conducted in centers in Australia, Canada, Israel, and the United States and is expected to enroll 31497 patients. If the results of INFORM indicate that shorter storage red blood cell transfusion is associated with superior outcomes compared with standard issue red blood cell transfusion, consideration may be given to shortening blood storage times. If, in contrast, the INFORM trial provides no evidence of harm from longer storage red blood cells, clinicians and patients may be reassured that current blood inventory management strategies are appropriate.
Publisher: Wiley
Date: 08-1985
DOI: 10.1111/J.1445-5994.1985.TB02759.X
Abstract: The influence of the xanthine derivative pentoxifylline ('Trental' or BL191 Hoechst-Roussel) on exercise tolerance was measured in 38 subjects with stable, severe to moderately severe, intermittent claudication who completed a randomised, double-blind, placebo controlled, cross-over clinical trial. Patients received placebo tablets or 400 mg slow-release pentoxifylline tablets ('Trental 400') twice a day for one week, followed by three times daily for seven weeks, and then crossed over to receive the alternate preparation for another eight weeks. Claudication distance and walking distance were measured on a treadmill before starting treatment and again at four-week intervals during the trial. At the same times, red blood cell filterability, plasma fibrinogen concentration and blood viscosity, resting and post-ischemic calf muscle blood flow, and the resting and post-exercise ankle/brachial systolic pressure ratio were also measured. In this study, the observed effects of pentoxifylline treatment were no greater than those of placebo, even though serum levels of pentoxifylline and its hydroxy-metabolite were within the anticipated range. This was shown by a 'therapeutic effect ratio' of 0.98 for treadmill claudication distance and 0.96 for treadmill walking distance after within-patient analysis at the end of the cross-over (where a ratio of 1.0 means the test drug and placebo effects are identical). These ratios have 95% confidence limits of 0.72-1.34 and 0.74-1.25, respectively.
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1111/J.1538-7836.2009.03635.X
Abstract: It remains unclear whether a single complete ultrasound examination, which detects calf vein thrombosis, is as safe as a baseline rapid ultrasound examination, repeated after 1 week when negative, which examines the veins in the groin and the knee. Therefore, we compared the safety and feasibility of two diagnostic ultrasound strategies, involving rapid and complete compression ultrasound (CUS) examination. Consecutive patients with suspected deep vein thrombosis (DVT) underwent clinical probability assessment. In patients with an unlikely clinical probability and a normal D-dimer finding, DVT was considered to be excluded. All others were randomized to undergo a rapid or a single complete CUS examination. Patients in whom DVT was excluded were followed for 3 months to assess the incidence of venous thromboembolism (VTE). A total of 1002 patients were included. A clinical decision rule indicating DVT to be unlikely and a normal D-dimer finding occurred in 481 patients (48%), with a VTE incidence of 0.4% [95% confidence interval (CI) 0.05-1.5%] during follow-up. DVT was confirmed in 59 of the 257 patients (23%) who underwent rapid CUS examination, and in 99 of the 264 patients (38%) who underwent complete CUS examination. VTE during follow-up occurred in four patients (2.0% 95% CI 0.6-5.1%) in the rapid CUS arm, and in two patients (1.2% 95% CI 0.2-4.3%) in the complete CUS arm. A diagnostic strategy with a clinical decision rule, a D-dimer test and a CUS examination is safe and efficient. Both the rapid and the complete CUS test are comparable and efficient strategies, with differing advantages and disadvantages.
Publisher: AMPCo
Date: 05-1986
Publisher: AMPCo
Date: 12-1969
Publisher: Springer Science and Business Media LLC
Date: 02-06-2016
DOI: 10.1007/S40266-016-0378-X
Abstract: Half of all patients with acute venous thromboembolism are aged over 70 years they then face the added hazard of an age-related increase in the incidence of major bleeding. This makes it even more important to weigh the balance of benefit and risk when considering anticoagulant treatment and treatment duration. Traditional treatment with a heparin (usually low molecular weight) followed by a vitamin K antagonist such as warfarin is effective but is often complicated, especially in the elderly. The direct-acting oral anticoagulants (DOACs), i.e. the thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban, apixaban and edoxaban, are given in fixed doses, do not need laboratory monitoring, have fewer drug-drug interactions and are therefore much easier to take. Randomised trials, their meta-analyses and 'real-world' data indicate the DOACs are no less effective than warfarin (are non-inferior) and probably cause less major bleeding (especially intracranial). It seems the relative safety of DOACs extends to age above 65 or 70 years, although bleeding becomes more likely regardless of the chosen anticoagulant. Renal impairment, comorbidities (especially cancer) and interventions are special hazards. Ways to minimise bleeding include patient selection and follow-up, education about venous thromboembolism, anticoagulants, drug interactions, regular checks on adherence and avoiding needlessly prolonged treatment. The relatively short circulating half-lives of DOACs mean that time, local measures and supportive care are the main response to major bleeding. They also simplify the management of invasive interventions. An antidote for dabigatran, idarucizumab, was recently approved by regulators, and a general antidote for factor Xa inhibitors is in advanced development.
Publisher: Massachusetts Medical Society
Date: 17-08-1972
Publisher: Massachusetts Medical Society
Date: 06-08-2009
Publisher: Georg Thieme Verlag KG
Date: 2014
DOI: 10.1160/TH14-08-0671
Abstract: Thrombosis is a common pathology underlying ischaemic heart disease, ischaemic stroke, and venous thromboembolism (VTE). The Global Burden of Disease Study 2010 (GBD 2010) documented that ischaemic heart disease and stroke collectively caused one in four deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability. We performed a systematic review of the literature on the global disease burden due to VTE in low, middle and high income countries. Studies from Western Europe, North America, Australia, and Southern Latin America (Argentina) yielded consistent results with annual incidences ranging from 0.75 to 2.69 per 1,000 in iduals in the population. The incidence increased to between 2 and 7 per 1,000 among those 70 years of age or more. Although the incidence is lower in in iduals of Chinese and Korean ethnicity, their disease burden is not low because of population aging. VTE associated with hospitalisation was the leading cause of disability-adjusted-lifeyears (DALYs) lost in low and middle income countries, and second in high income countries, responsible for more DALYs lost than nosocomial pneumonia, catheter-related blood stream infections, and adverse drug events. VTE causes a major burden of disease across low, middle, and high income countries. More detailed data on the global burden of VTE should be obtained to inform policy and resource allocation in health systems, and to evaluate if improved utilisation of preventive measures will reduce the burden. Note: The copyright for the article is being held by the International Society on Thrombosis and Haemostasis under a CC-BY-NC-ND license.
Publisher: Elsevier BV
Date: 09-1998
DOI: 10.1016/S0950-3536(98)80088-7
Abstract: Streptokinase, urokinase, tissue plasminogen activator and similar drugs can all cause lysis of venous thrombi and pulmonary emboli, but there is small evidence that accelerated lysis achieves a significantly better clinical outcome, on average, in the shorter or longer term, than heparin alone. Thrombolytic therapy for deep leg vein thrombosis aims to restore flow and to preserve venous valves, and so to prevent chronic post-phlebitic disability, but no trial has convincingly demonstrated that the last can be achieved in more than a few patients. Only a small minority of people with extensive proximal thrombosis develop disabling post-phlebitic venous insufficiency, and there are no good clinical predictors of this outcome. As a result, any widespread use of thrombolytics would bring an immediate risk of major bleeding to many people who will never be destined to develop a clinically important problem. Thrombolytic therapy after venous thrombosis should be avoided except, perhaps, in a few carefully selected patients with severe obstruction. The case for using thrombolytics after recent pulmonary embolism is strongest in the limited number of patients with ongoing hypoxia, respiratory distress, pulmonary hypertension and right heart failure, because thrombolytic therapy often achieves an impressive and almost immediate clinical benefit in this clinical setting. Whether early relief from pulmonary artery obstruction translates into longer-term advantage over heparin remains uncertain, however, because no comparative trial has ever shown these drugs to reduce mortality after pulmonary embolism. In all cases, both the physician and the patient must balance the certainty of an immediate bleeding risk against the uncertainty of a better than marginal real benefit.
Publisher: Massachusetts Medical Society
Date: 03-2001
Publisher: BMJ
Date: 26-01-2006
Publisher: Georg Thieme Verlag KG
Date: 15-10-2008
Abstract: The authors reviewed the morbidity and mortality of surgical resection of the descending thoracic and thoracoabdominal aorta using the cl -and-sew technique. Paraplegia remains a devastating complication after thoracoabdominal aortic resection, despite many strategies for spinal cord protection. Because of its simplicity, cl and sew has been the preferred technique at the University of Virginia for the thoracoabdominal aortic resection when proximal control is possible. Between 1987 and 1994, the authors reviewed 91 consecutive patients who underwent thoracic aortic resection using cl -and-sew techniques without any additional adjuncts for spinal cord protection. The average age of patients was 60.8 years 57.1% were male. No intraoperative deaths occurred. In-hospital mortality was 13% (12/91), with an overall incidence of postoperative spinal cord injury manifested as paraparesis or paraplegia of 9.9% (9/91). Eighty-nine percent (81/91) of all repairs were completed with aortic cl times of 40 minutes or less, and nearly six out of ten were completed in 30 minutes or less (53/91). Cross-cl times were not significantly different between those patients who sustained neurologic injury and those who had no deficits. The authors conclude that cl and sew is still a viable technique for thoracoabdominal aortic resection. Nearly all resections can be completed within 40 minutes of aortic occlusion. However, the "safe" duration of thoracic aortic occlusion remains unknown, and spinal cord injury can occur even with short cl times. Reproducible, safe, and technically simple means of spinal cord protection must be developed.
Publisher: Wiley
Date: 02-04-2009
Publisher: American College of Physicians
Date: 19-12-2017
Publisher: Elsevier BV
Date: 10-1989
DOI: 10.1016/0049-3848(89)90165-5
Abstract: We have measured the effects of Org 10172 (a mixture of naturally occurring glycosaminoglycans derived from hog intestinal mucosa) on blood loss after transurethral prostatectomy (TURP), using doses which are likely to prevent postoperative venous thrombosis (VT). 48 patients entered a double-blind randomised pilot study: 18 were given subcutaneous (sc) injections of a placebo and 30 received sc Org 10172 (750 anti-Xa units/day, 500 units twice daily (bid), or 750 units bid, starting just before TURP and continued until discharge 10 patients per group). No Org 10172 regimen increased peroperative blood loss but all caused a similar trend towards increased urinary bleeding after surgery. Since there was no apparent dose effect gradient, it was decided to pool the data from all three dosing blocks: this analysis showed that Org 10172 increased geometric mean blood loss during the first 2 days after surgery from 10.4 gm hemoglobin (Hgb range = 3.2-71) to 20.5 gm Hgb (range = 1.9-147) (p = .005), an effect which retained its significance after allowing for two other major determinants of postoperative bleeding, the weight of prostate resected and the length of surgery, and also when pooling was restricted to the twice daily Org 10172 injection groups and their corresponding controls. Bleeding was not severe, but our results indicate a need for caution when considering the use of Org 10172 in this setting.
Publisher: AMPCo
Date: 2005
Publisher: Wiley
Date: 03-1974
DOI: 10.1111/J.1749-6632.1974.TB14458.X
Abstract: The thymus generates a lineage-committed subset of regulatory T-cells (Tregs), best identified by the expression of the transcription factor FOXP3. The development of thymus-derived Tregs is known to require high-avidity interaction with MHC-self peptides leading to the generation of self-reactive Tregs fundamental for the maintenance of self-tolerance. Notwithstanding their crucial role in the control of immune responses, human thymic Treg differentiation remains poorly understood. In this mini-review, we will focus on the developmental stages at which Treg lineage commitment occurs, and their spatial localization in the human thymus, reviewing the molecular requirements, including T-cell receptor and cytokine signaling, as well as the cellular interactions involved. An overview of the impact of described thymic defects on the Treg compartment will be provided, illustrating the importance of these in vivo models to investigate human Treg development.
Publisher: Elsevier BV
Date: 09-1984
DOI: 10.1016/0049-3848(84)90283-4
Abstract: The effect of preoperative treatment with an estrogen containing oral contraceptive on the incidence of postoperative thrombosis (detected with 125I-fibrinogen leg scanning) was examined in 221 patients aged 18-49 years who had elective or emergency general intra-abdominal or gynecologic surgery, 99 of whom were taking an oral contraceptive before their operation. Eighty-five percent of the contraceptive treated patients had taken their preparation until 1-7 days before surgery and the rest until within a month of surgery 81% were taking preparations containing 30 or 50 micrograms estrogen. Postoperative thrombosis developed in 1 of the 122 patients who were not taking a contraceptive and in none of the 99 contraceptive treated patients. As the 95% confidence limits for the 0% thrombosis rate observed in the contraceptive treated patients are 0-3.7%, the added risk of postoperative thrombosis attributable to oral contraceptive treatment before surgery is very small in young women who are otherwise at low risk of thrombosis. Plasma antithrombin level (by immunoassay), antithrombin activity (by chromogenic substrate assay), and antifactor Xa activity (by clotting assay), were measured before surgery in 81 patients, 42 of whom had been taking an oral contraceptive. Contraceptive treatment significantly reduced all 3 assay results. Its most marked effect was on antifactor Xa activity, which was reduced by contraceptive treatment from 103 +/- 24% (range 68 - 172%) to 81 +/- 27% (range 24 - 155% with less than 80% activity in 54%, and less than 50% activity in 15% of patients). These results suggest that reduced preoperative antifactor Xa activity has a low specificity for thrombosis after moderately extensive surgery in young, otherwise fit, oral contraceptive treated women. This test is therefore unlikely to be a clinically useful predictor for postoperative thrombosis in this group of patients.
Publisher: Wiley
Date: 06-2012
DOI: 10.1111/J.1445-5994.2012.02808.X
Abstract: Each year in Australia, about 1 in 1000 people develop a first episode of venous thromboembolism (VTE), which approximates to about 20,000 cases. More than half of these episodes occur during or soon after a hospital admission, which makes them potentially preventable. This paper summarises recommendations from the National Health and Medical Research Council's 'Clinical Practice Guideline for the Prevention of Venous Thromboembolism in Patients Admitted to Australian Hospitals' and describes the way these recommendations were developed. The guideline has two aims: to provide advice on VTE prevention to Australian clinicians and to support implementation of effective programmes for VTE prevention in Australian hospitals by offering evidence-based recommendations which local hospital guidelines can be based on. Methods for preventing VTE are pharmacological and/or mechanical, and they require appropriate timing, dosing and duration and also need to be accompanied by good clinical care, such as promoting mobility and hydration whilst in hospital. With some procedures or injuries, the risk of VTE is sufficiently high to require that all patients receive an effective form of prophylaxis unless this is contraindicated in other clinical settings, the need for prophylaxis requires in idual assessment. For optimal VTE prevention, all patients admitted to hospital should have early and formal assessments of: (i) their intrinsic VTE risk and the risks related to their medical conditions (ii) the added VTE risks resulting from surgery or trauma (iii) bleeding risks that would contraindicate pharmacological prophylaxis (iv) any contraindications to mechanical prophylaxis, culminating in (v) a decision about prophylaxis (pharmacological and/or mechanical, or none). The most appropriate form of prophylaxis will depend on the type of surgery, medical condition and patient characteristics. Recommendations for various clinical circumstances are provided as summary tables with relevance to orthopaedic surgical procedures, other types of surgery and medical inpatients. In addition, the tables indicate the grades of supporting evidence for the recommendations (these range from Grade A which can be trusted to guide practice, to Grade D where there is more uncertainty Good Practice Points are consensus-based expert opinions).
Publisher: Therapeutic Guidelines Limited
Date: 06-1998
Publisher: Georg Thieme Verlag KG
Date: 02-2005
Abstract: Current evidence indicates that prolonged air travel predisposes to venous thrombosis and pulmonary embolism. An effect is seen once travel duration exceeds 6 to 9 hours and becomes obvious in long-haul passengers traveling for 12 or more hours. A recent records linkage study found that increase in thrombosis rate among arriving passengers peaked during the first week and was no longer apparent after 2 weeks. Medium- to long-distance travelers have a 2- to 4-fold increase in relative thrombosis risk compared with nontravelers, but the averaged absolute risk is small (approximately one symptomatic event per 2 million arrivals, with a case-fatality rate of approximately 2%) and there is no evidence that thrombosis is more likely in economy class than in business- or first-class passengers. It remains uncertain whether and to what extent thrombosis risk is increased by short-distance air travel or prolonged travel by motorcar, train, or other means. Most travelers who develop venous thrombosis or pulmonary embolism also have one or more other predisposing risk factors that may include older age, obesity, recent injury or surgery, previous thrombosis, venous insufficiency, malignancy, hormonal therapies, or pregnancy. Limited (though theoretically plausible) evidence suggests that factor V Leiden and the prothrombin gene mutation predispose to thrombosis in otherwise healthy travelers. Given that very many passengers with such predispositions do not develop thrombosis, and a lack of prospective studies to link predisposition with disease, it is not now possible to allocate absolute thrombosis risk among intending passengers or to estimate benefit-to-risk ratios or benefit-to-cost ratios for prophylaxis. Randomized comparisons using ultrasound imaging indicate a measurable incidence of subclinical leg vein thrombosis after prolonged air travel, which appears to increase with travel duration and is reduced by graded pressure elastic support stockings. Whether this surrogate outcome measure translates into clinical benefit remains unknown, but support stockings are likely to be more effective and have less adverse effects than the use of aspirin.
Publisher: Massachusetts Medical Society
Date: 28-06-1973
DOI: 10.1056/NEJM197306282882619
Abstract: Bicyclic oxazaphospholidine monomers were used to prepare a series of phosphorothioate (PS)-modified gapmer antisense oligonucleotides (ASOs) with control of the chirality of each of the PS linkages within the 10-base gap. The stereoselectivity was determined to be 98% for each coupling. The objective of this work was to study how PS chirality influences biophysical and biological properties of the ASO including binding affinity (Tm), nuclease stability, activity in vitro and in vivo, RNase H activation and cleavage patterns (both human and E. coli) in a gapmer context. Compounds that had nine or more Sp-linkages in the gap were found to be poorly active in vitro, while compounds with uniform Rp-gaps exhibited activity very similar to that of the stereo-random parent ASOs. Conversely, when tested in vivo, the full Rp-gap compound was found to be quickly metabolized resulting in low activity. A total of 31 ASOs were prepared with control of the PS chirally of each linkage within the gap in an attempt to identify favorable Rp/Sp positions. We conclude that a mix of Rp and Sp is required to achieve a balance between good activity and nuclease stability.
Publisher: Massachusetts Medical Society
Date: 23-12-2010
Publisher: SAGE Publications
Date: 06-2003
DOI: 10.1345/APH.1A372
Abstract: To examine the time taken to reach a stable international normalized ratio (INR), as well as the incidence of overanticoagulation of an age-adjusted warfarin initiation protocol. Inpatients and outpatients commencing warfarin therapy at 2 teaching hospitals were dosed according to the age-adjusted protocol. Data were collected prospectively. Time to reach a stable INR of 2–3 and the number of patients experiencing an INR ≥4 during the first week of warfarin therapy. Seventy-three patients were assessed at the completion of the 4-day titration protocol, 63% had achieved a stable INR. After an additional 2 days of empiric dosage adjustment by the attending physician, 86% of the subjects demonstrated a stable INR. Five patients (7%) experienced an INR ≥4. These patients had a nonsignificant trend toward a lower plasma albumin level compared with other patients (p = 0.057, Student's t-test). The INR-driven dose adjustments on days 3 and 4 of this protocol coped with other variables that have been shown to affect maintenance warfarin dosing. These included weight, gender, pharmacologic factors affecting clearance, and the presence of certain predesignated risk factors. The age-adjusted dosing protocol rapidly achieved a stable INR with minimal overanticoagulation. Patients with low serum albumin levels ( .0 g/dL) may be sensitive to the effects of warfarin during the loading phase.
Publisher: Georg Thieme Verlag KG
Date: 02-2005
Abstract: Thrombophilias may be inherited or acquired, continuing or transient, and may contribute strongly or weakly to thrombosis. They may predispose to venous thromboembolism alone or also to artery occlusion. Advice on management must recognize these variations. The presence of an inherited thrombophilia should not alter the intensity of anticoagulant therapy, given that antithrombin, protein C, or protein S deficiency, factor V Leiden, and the prothrombin G20210A mutation are not unusually anticoagulant resistant. However, they can increase the optimal treatment duration after a first thromboembolic event. Optimal duration depends on the balance between thrombosis risk off treatment and bleeding risk during extended anticoagulant therapy, and needs to be separately estimated for each in idual with thrombosis and thrombophilia. The higher the thrombosis risk and the lower the bleeding risk, the longer the optimal treatment duration. This balance favors continued (but perhaps not indefinite) therapy in antithrombin, protein C, and protein S deficiency, and perhaps also in patients with the factor V Leiden or prothrombin mutations if their bleeding risk is low. Thrombosis that complicates active malignancy, the antiphospholipid syndrome, or heparin-induced thrombocytopenia needs special consideration: recent clinical trials suggest that low molecular weight heparins are more effective than warfarin in thrombosis with cancer, and that a more intense warfarin effect is not needed for patients with antiphospholipid syndrome and thrombosis. Debate continues about the place of screening for presymptomatic but affected relatives of patients with thrombosis and an inherited predisposition. It is essential that any family testing be done only with the informed consent of all concerned. Given consent, there is general support for family testing in antithrombin, protein C, or protein S deficiency and where the factor V Leiden or prothrombin mutation is strongly penetrant and expressed. There is, however, a strong argument that any testing in families in which clotting factor polymorphisms are weakly expressed should be restricted to young women when they consider hormonal contraception or pregnancy, given that these acquired factors multiply the risk.
Publisher: AMPCo
Date: 03-2013
DOI: 10.5694/MJA12.10614
Abstract: • Despite the associated bleeding risk, warfarin is the most commonly prescribed anticoagulant in Australia and New Zealand. Warfarin use will likely continue for anticoagulation indications for which novel agents have not been evaluated and among patients who are already stabilised on it or have severe renal impairment. • Strategies to manage over-warfarinisation and warfarin during invasive procedures can reduce the risk of haemorrhage. • For most warfarin indications, the target international normalised ratio (INR) is 2.0-3.0 (venous thromboembolism and single mechanical heart valve excluding mitral). For mechanical mitral valve or combined mitral and aortic valves, the target INR is 2.5-3.5. • Risk factors for bleeding with warfarin use include increasing age, history of bleeding and specific comorbidities. • For patients with elevated INR (4.5-10.0), no bleeding and no high risk of bleeding, withholding warfarin with careful subsequent monitoring seems safe. • Vitamin K1 can be given to reverse the anticoagulant effect of warfarin. When oral vitamin K1 is used for this purpose, the injectable formulation, which can be given orally or intravenously, is preferred. • For immediate reversal, prothrombin complex concentrates (PCC) are preferred over fresh frozen plasma (FFP). Prothrombinex-VF is the only PCC routinely used for warfarin reversal in Australia and New Zealand. It contains factors II, IX, X and low levels of factor VII. FFP is not routinely needed in combination with Prothrombinex-VF. FFP can be used when Prothrombinex-VF is unavailable. Vitamin K1 is essential for sustaining the reversal achieved by PCC or FFP. • Surgery can be conducted with minimal increased risk of bleeding if INR ≤ 1.5. For minor procedures where bleeding risk is low, warfarin may not need to be interrupted. If necessary, warfarin can be withheld for 5 days before surgery, or intravenous vitamin K₁ can be given the night before surgery. Prothrombinex-VF use for warfarin reversal should be restricted to emergency settings. Perioperative management of anticoagulant therapy requires an evaluation of the risk of thrombosis if warfarin is temporarily stopped, relative to the risk of bleeding if it is continued or modified.
Publisher: Elsevier BV
Date: 03-1980
DOI: 10.1016/S0140-6736(80)92783-X
Abstract: Mucormycosis is a life-threatening respiratory fungal infection predominantly caused by Rhizopus species. Mucormycosis has incompletely understood pathogenesis, particularly how abnormalities in iron metabolism compromise immune responses. Here we show how, as opposed to other filamentous fungi, Rhizopus spp. establish intracellular persistence inside alveolar macrophages (AMs). Mechanistically, lack of intracellular swelling of Rhizopus conidia results in surface retention of melanin, which induces phagosome maturation arrest through inhibition of LC3-associated phagocytosis. Intracellular inhibition of Rhizopus is an important effector mechanism, as infection of immunocompetent mice with swollen conidia, which evade phagocytosis, results in acute lethality. Concordantly, AM depletion markedly increases susceptibility to mucormycosis. Host and pathogen transcriptomics, iron supplementation studies, and genetic manipulation of iron assimilation of fungal pathways demonstrate that iron restriction inside macrophages regulates immunity against Rhizopus. Our findings shed light on the pathogenetic mechanisms of mucormycosis and reveal the role of macrophage-mediated nutritional immunity against filamentous fungi.
Publisher: Georg Thieme Verlag KG
Date: 2007
DOI: 10.1160/TH06-10-0601
Abstract: The value of vein ultrasonography for diagnosis of symptomatic deep vein thrombosis (DVT) is widely accepted. We are unaware of published data comparing ultrasonography with the “gold standard” of venography for DVT diagnosis in asymptomatic persons in the patient group of acutely ill medical patients. It was the objective of this study to evaluate sensitivity and specificity of compression ultrasound (CUS) examinations in the diagnosis of proximal and distal DVT in acutely ill medical patients [with congestive heart failure (NYHA class III and IV), exacerbations of respiratory disease, infectious disease, and inflammatory diseases] considered to be at moderate risk of venous thromboembolism (VTE). CUS examination was performed prior to ascending venography on day 6–15 of the hospital stay. Both investigations were done on the same day, each interpreted without knowledge of the other’s result. Proximal and calf veins were separately evaluated. Technically satisfactory venography was obtained in 160 patients. In 12 of 160 patients (7.5%, 95% CI = [4.0%-12.7%]), venography confirmed the presence of DVT, all of which was asymptomatic. Proximal DVT was detected in five patients (3.1%, 95% CI = [1.0%- 7.1%]) and distal DVT in seven patients (4.4%, 95% CI = [1.8% – 8.8%]). CUS of proximal veins was technically satisfactory in all 160 patients and CUS of distal veins in 150 patients. In three of five patients with veongraphically proven proximal DVT, the diagnosis was confirmed by CUS (sensitivity 60%, 95%CI = [23%-88%]). In one patient, the CUS was false positive (specificity 99.4%, 95%CI = [96%-99%]). Positive and negative predictive values (PPV and NPV) of CUS in the diagnosis of proximal DVT were 75% (95%CI = [30%-95%]) and 98% (95% CI = [95%-99%]), respectively. In two of seven patients with venographically proven calf DVT, the diagnosis was confirmed by CUS (sensitivity 28.6%, 95%CI = [8%-64%]) and in two patients, CUS was false positive (specificity 98.6, 95%CI = [95%-99%]). PPV and NPV of CUS in diagnosis of distal DVT were 50% (95%CI = [15–85%]) and 96% (95% CI = [92%-98%]), respectively. In conclusion, CUS underestimates the incidence of proximal and distal DVT compared to contrast venography in acutely ill medical patients without thrombosis symptoms.
Publisher: Springer Science and Business Media LLC
Date: 09-1995
DOI: 10.1007/BF00302125
Publisher: Elsevier BV
Date: 04-0012
DOI: 10.1016/J.JCRC.2005.09.002
Abstract: Internationally, there is practice variation concerning optimal thromboprophylaxis for patients in the intensive care unit (ICU). The current practice in Australia and New Zealand is unknown. We conducted a self-administered e-mail survey of 22 Australian and New Zealand ICUs expressing interest in participating in a proposed international randomized trial (PROphylaxis for ThromboEmbolism in Critical Care Trial). Our response rate was 95.4% (95% CI, 77%-100%). Of participating ICUs, 90.5% (95% CI, 70%-99%) used subcutaneous unfractionated heparin for routine thromboprophylaxis in ICU patients. Low-molecular-weight heparin was reserved for specific high-risk patients in many units. Routine thromboprophylaxis for ICU patients in Australia and New Zealand is similar to Canada but different to France. Optimal thromboprophylaxis for ICU patients is currently unclear in the absence of randomized trial data.
Publisher: SAGE Publications
Date: 2015
DOI: 10.4137/CCREP.S27992
Abstract: Rivaroxaban is an orally active direct factor Xa inhibitor used to treat venous thromboembolism with approved starting dose of 15 mg twice-daily. We present a case of an accidental overdose in a patient with pulmonary thromboembolism, when the patient received two 150 mg doses of rivaroxaban, instead of 15 mg as prescribed, given 12 hours apart. This error was recognised ten minutes after the second dose, when 50 gm oral activated charcoal was given. Rivaroxaban was stopped and rivaroxaban concentrations, INR, and APTT were monitored. The overdose was uncomplicated and 15 mg twice-daily rivaroxaban was restarted on day two. Apparently unlikely and potentially hazardous dispensing errors do happen. Each oral anticoagulant has a different dosing schedule. In our patient, the prescription for 15 mg twice-daily rivaroxaban was misread as 150 mg twice-daily (a correct dose for dabigatran in atrial fibrillation). Such errors are preventable. Prompt administration of activated charcoal under monitoring of a specific rivaroxaban assay can greatly help management of unusual situations like this one.
Publisher: BMJ
Date: 27-07-1991
Publisher: Elsevier BV
Date: 04-1974
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.THROMRES.2008.10.006
Abstract: To assess clinical usefulness of CoaguChek S and XS monitors to measure International Normalised Ratio (INR) when starting warfarin in community patients. INR in consecutive patients starting warfarin plus enoxaparin was measured in the laboratory and on capillary blood at home using CoaguChek S or XS point of care (POC) devices. INR was measured daily until >2.0 for 2 consecutive readings. Linear regression and Bland Altman plots were derived to compare POC with laboratory INR. Percentages of POC measurements within 0.5 and 0.8 units of laboratory INR 3.5 were calculated. Clinical utility was assessed using previously reported criteria. 200 CoaguChek S and 337 CoaguChek XS results were obtained from 57 and 98 patients respectively and paired with laboratory values. Correlation was acceptable between CoaguChek S and laboratory INRs (r(2)=0.7732), and excellent between CoaguChek XS and laboratory INRs (r(2)=0.9514). Bland-Altman plots showed an increasing difference between laboratory INR above 3.0 for CoaguChek S INRs but no systematic bias with increasing CoaguChek XS INRs. 83.5% of CoaguChek S and 93.5% of CoaguChek XS INRs were within 0.5 units of laboratory INR. 90% of CoaguChek S and 99.4% of the CoaguChek XS INRs were within 0.8 units of laboratory INR. Clinical agreement occurred in 89% and 99.7% of cases by expanded criteria and 82% and 99.4% of cases by narrow criteria when using CoaguChek S and CoaguChek XS respectively. The CoaguChek XS is suitable for outpatient INR monitoring when starting warfarin.
Publisher: Georg Thieme Verlag KG
Date: 2014
DOI: 10.1160/TH13-04-0296
Abstract: This double-blind, double-dummy, randomised, phase IIb study (NCT00902928) evaluated different dosing regimens of darexaban compared with enoxaparin (randomised 1:1:1:1:1 to 15 mg twice daily [bid], 30 mg once daily [qd], 30 mg bid or 60 mg qd or enoxaparin 40 mg qd) in patients undergoing elective total hip arthroplasty. Patients, investigators, pharmacists and sponsor were all blinded to treatment allocation. Darexaban administration started 6-10 hours (h) post-surgery. Enoxaparin 40 mg qd administration started 12 ± 2 h before surgery. Treatment continued for 35 days. Bilateral venography was performed on Day 10 ± 2. The primary efficacy outcome was total VTEs (composite of proximal/distal deep-vein thrombosis, pulmonary embolism) or death, at Day 12. Total VTE rates were similar across all groups. There was no apparent difference in efficacy between onceand twice-daily darexaban (odds ratio [OR] 1.00 95% confidence interval [CI] 0.71–1.42 p=0.988), or total daily dose (30 mg/day vs 60 mg/day OR 0.81 95% CI 0.57–1.15 p=0.244). There was no significant difference in major and/or clinically relevant non-major bleeding between darexaban qd or bid, or between total daily doses of 30 mg or 60 mg, and also for any dosing regimen of darexaban vs enoxaparin. Darexaban was well tolerated, without signs of liver toxicity. In conclusion, darexaban, administered qd or bid, and at total daily doses of 30 mg or 60 mg, appears to be effective for VTE prevention and was well tolerated. Data suggest no significant differences between a once- or twice-daily dosing regimen.
Publisher: Massachusetts Medical Society
Date: 26-07-1973
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-1977
DOI: 10.1212/WNL.27.5.435
Abstract: In a randomized study of 128 patients, we evaluated intermittent pneumatic compression of the calf in the prevention of leg scan-detected venous thrombosis in intracranial disease. Pneumatic compression of the calf for 5 days reduced the rate of venous thrombosis from 12 of 63 control patients (19.1 percent) to one of 65 patients (1.5 percent) given prophylaxis (p = 0.00082). In patients who had craniotomy for brain tumor, subarachnoid hemorrhage, or subdural hematomas, calf compression reduced the incidence of venous thrombosis from nine of 49 control patients (18.4 percent) to one of 53 patients (1.9 percent) given prophylaxis (p - 0.0051). In patients who remained at risk after 5 days, the rate of venous thrombosis was no different in the control group than in the group that had received prophylaxis.
Publisher: Schattauer GmbH
Date: 1975
Abstract: Patients with venous thromboembolism differ considerably in their heparin response and requirements. We have investigated the mechanism for, and practical consequence of this variation in 20 patients with proven venous thromboembolism (VTE). A standard i/v heparin dose 70 U/kg bolus followed 90 min later by 400 U/kg/24 hrs. by continuous infusion was given. Blood was drawn pre heparin and 15, 45 and 90 min post bolus and then during maintenance infusion for the following tests: heparin tolerance, activated partial thromboplastin time (APTT), heparin level. In addition heparin recovery and clearance were calculated. There were large inter-in idual variations in the anticoagulant response to heparin which was due in part to differences in rates of heparin inactivation and clearance and in part to marked differences in the APTT response to heparin. For ex le, the heparin level at 15 min post bolus varied from 0.2 U to 0.9 U and during maintenance from 0.0 U to 0.5 U. The APTT varied from 45 to 200 sees, at 15 min and 38 to 96 sees during maintenance infusion. In addition the APTT prolongation over the pre-treatment APTT varied up to 9 fold between patients for a given heparin concentration. There was a marked and significant difference in heparin half life between patients with venous thrombosis (70±17 min) and pulmonary embolism (PE) (38±1 min) p 0.005. This rapid clearance in PE may be due to release of antiheparin activity from platelets which interact with thrombin onto the surface of the embolus. The results suggest that the heparin dose should be in idualized in VTE and that larger doses should be initially given to patients with PE.
Publisher: BMJ
Date: 12-1980
Abstract: The effects have been studied of diluent, heparin activity after dilution, container, and pH on the stability of heparin solutions stored under conditions resembling those present during heparin infusion by intravenous drip or syringe pump. Heparin activity was measured by activated partial thromboplastin time and thrombin clotting time (and, in one set of studies, also by factor Xa inhibitor assay and protamine sulphate neutralisation). Heparin activity was stable for 6 hours regardless of storage conditions. After 24 hours heparin activity was stable when the drug was diluted in 0.9% saline and stored in plastic, but a small loss of activity was observed in several studies after dilution in 5% dextrose or storage in glass. A more extensive comparison confirmed a 3-5% loss in heparin activity over 24 hours after dilution in 5% dextrose. Changing the pH to 3.5 or 10.0 had little effect on storage stability. We conclude that heparin activity in vitro remains stable during short infusions but recommend dilution in 0.9% saline and a plastic container when a heparin solution is infused over 24 hours.
Publisher: Elsevier BV
Date: 12-2007
DOI: 10.1111/J.1538-7836.2007.02764.X
Abstract: Heparins and warfarin are currently used as venous thromboembolism (VTE) prophylaxis in surgery. Inhibition of factor (F) Xa provides a specific mechanism of anticoagulation and the potential for an improved benefit-risk profile. To evaluate the safety and efficacy of apixaban, a potent, direct, oral inhibitor of FXa, in patients following total knee replacement (TKR), and to investigate dose-response relationships. A total of 1238 patients were randomized to one of six double-blind apixaban doses [5, 10 or 20 mg day(-1) administered as a single (q.d.) or a twice-daily ided dose (b.i.d.)], enoxaparin (30 mg b.i.d.) or open-label warfarin (titrated to an International Normalized Ratio of 1.8-3.0). Treatment lasted 10-14 days, commencing 12-24 h after surgery with apixaban or enoxaparin, and on the evening of surgery with warfarin. The primary efficacy outcome was a composite of VTE (mandatory venography) and all-cause mortality during treatment. The primary safety outcome was major bleeding. A total of 1217 patients were eligible for safety and 856 patients for efficacy analysis. All apixaban groups had lower primary efficacy event rates than either comparator. The primary outcome rate decreased with increasing apixaban dose (P = 0.09 with q.d./b.i.d. regimens combined, P = 0.19 for q.d. and P = 0.13 for b.i.d. dosing).A significant dose-related increase in the incidence of total adjudicated bleeding events was noted in the q.d. (P = 0.01) and b.i.d. (P = 0.02) apixaban groups there was no difference between q.d. and b.i.d. regimens. Apixaban in doses of 2.5 mg b.i.d. or 5 mg q.d. has a promising benefit-risk profile compared with the current standards of care following TKR.
Publisher: Georg Thieme Verlag KG
Date: 2016
DOI: 10.1160/TH15-11-0892
Abstract: Edoxaban is a once-daily direct oral anticoagulant (DOAC). The Hokusai-VTE study revealed that, after initial treatment with heparin, edoxaban was non-inferior to and safer than vitamin K antagonists (VKA) in the prevention of recurrent deep-vein thrombosis and pulmonary embolism. This is the first report on the clinical relevance and management of bleeding events with edoxaban. All major bleeding events were classified blindly by three study-independent adjudicators. Predefined criteria were used to classify severity of clinical presentation and, separately, the clinical course and outcome into four categories. Major bleeding occurred in 56 patients treated with edoxaban and 65 patients treated with VKA. The severest categories (3 or 4) of the clinical presentation were assigned to 46 % of the major bleeding episodes in edoxaban recipients versus 58 % of the major bleeds in VKA recipients (odds ratio [OR] 0.62, 95 % confidence interval [CI] 0.30–1.27, p = 0.19). Clinical course was classified as severe (category 3 or 4) in 23 % of the edoxaban and 29 % of the VKA associated bleeds (OR 0.73, 95 % CI 0.32–1.66, p = 0.46). In conclusion, edoxaban associated major bleeding events have a comparable clinical presentation and course to major bleeds with VKA in patients treated for venous thromboembolism in the Hokusai-VTE study. These results may assure physicians that it is safe to prescribe this medication. If a major bleeding during edoxaban treatment occurs, its clinical presentation and clinical course are not worse than in VKA-treated patients.
Publisher: Elsevier BV
Date: 07-1990
DOI: 10.1016/S0950-3536(05)80023-X
Abstract: For 50 years, the key to successfully preventing venous thrombosis (VT) or pulmonary embolism (PE) among high-risk patients has been the judicious use of anticoagulants: first through full doses of oral anticoagulants and more recently through low-dose heparin prophylaxis. Low-dose heparin has become the standard of comparison for other preventive methods, since it is relatively safe and simple, its ability to prevent approximately 65% of the subclinical VT found by leg scanning after elective general surgery is well known, and recent meta-analysis of the many pertinent published clinical trials (large and small) strongly suggests a much greater benefit: a 65% reduction in the risk of postoperative death from major PE. In addition, there are trials that have also found low-dose heparin to be effective in general medical patients, although its value in this clinical setting is much less well documented. Although several effective approaches other than low-dose heparin are available, many of these tend to be either more cumbersome (intermittent external leg compression) or probably less powerful (graded pressure elastic stockings). There are situations where low-dose heparin prophylaxis fails, most obviously after orthopaedic surgery where the use of more complex regimens, including adjusted-dose heparin treatment and various schedules of warfarin prophylaxis, becomes appropriate. Recent progress has come from the intensive clinical exploration of various low molecular weight heparin fractions or fragments which appear to be effective after once daily administration to general surgical patients and show great promise of effectiveness and safety after hip surgery. The level of warfarin effect needed for VT prophylaxis has also been reinvestigated, with trials suggesting a need for less warfarin and a lower prothrombin time effect than was previously thought to be appropriate. Given that any attempts to minimize mortality from PE in hospital patients must rely on the widespread and systematic use of simple, safe, and cost-effective preventive methods, it is hoped that these advances will help move anticoagulant prophylaxis further out of the realm of clinical research and into that of common clinical practice.
Publisher: Springer Science and Business Media LLC
Date: 08-2015
DOI: 10.1007/S11239-012-0780-0
Abstract: Venous thromboembolism (VTE) prophylaxis is suboptimal in American hospitals despite long-standing evidence-based recommendations. Data from observational studies indicate a lower uptake of effective prophylaxis in patients hospitalized with medical versus surgical conditions. Reluctance to use prophylaxis in medical patients has been attributed to difficulty in identifying at-risk patients and balancing risks of bleeding against occurrence of VTE. Several risk-assessment models (RAMs) have been proposed to assist physicians in identifying non-surgical patients who need prophylaxis. We conducted a systematic review of published RAMs, based on objective criteria, to determine whether any RAM is validated sufficiently to be employed in clinical practice. We identified 11 RAMs, six derived from primary data and five based on expert opinion. The number, types, and strength of association of VTE risk predictors were highly variable. The variability in methods and outcome measurement precluded pooled estimates of these different models. Published RAMs for VTE lack generalizability and adequate validation. As electronic health records become more ubiquitous, validated dynamic RAMs are needed to assess VTE risk at the point-of-care in real time.
Publisher: Elsevier BV
Date: 03-1972
DOI: 10.1016/0002-8703(72)90428-0
Abstract: Rapid recovery is desirable after neurosurgery as it enables early post-operative neurological evaluation and prompt management of complications. Studies have been rare comparing the recovery characteristics in paediatric neurosurgical patients. Hence, this study was carried out to compare the effect of sevoflurane and desflurane anaesthesia on emergence and extubation in children undergoing spinal surgery. Sixty children, aged 1-12 years, undergoing elective surgery for lumbo-sacral spinal dysraphism were enrolled. Anaesthesia was induced with sevoflurane using a face mask. The children were then randomised to receive either sevoflurane or desflurane with oxygen and nitrous oxide, fentanyl (1 μg/kg/h) and rocuronium. The anaesthetic depth was guided by bispectral index (BIS(®)) monitoring with a target BIS(®) between 45 and 55. Perioperative data with regard to demographic profile, haemodynamics, emergence and extubation times, modified Aldrete score (MAS), pain (objective pain score), agitation (Cole's agitation score), time to first analgesic and complications, thereof, were recorded. Statistical analysis was done using STATA 11.2 (StataCorp., College Station, TX, USA) and data are presented as median (range) or mean ± standard deviation. The demographic profile, haemodynamics, MAS, pain and agitation scores and time to first analgesic were comparable in between the two groups (P > 0.05). The emergence time was shorter in desflurane group (2.75 [0.85-12] min) as compared to sevoflurane (8 [2.5-14] min) (P < 0.0001). The extubation time was also shorter in desflurane group (3 [0.8-10] min) as compared to the sevoflurane group (5.5 [1.2-14] min) (P = 0.0003). Desflurane provided earlier tracheal extubation and emergence as compared to sevoflurane in children undergoing surgery for lumbo-sacral spinal dysraphism.
Publisher: American Medical Association (AMA)
Date: 03-05-1976
Publisher: Elsevier BV
Date: 08-2001
Publisher: Springer Science and Business Media LLC
Date: 05-1990
DOI: 10.1007/BF02274825
Publisher: Elsevier BV
Date: 2012
Publisher: Wiley
Date: 06-1977
Publisher: Georg Thieme Verlag KG
Date: 2017
DOI: 10.1160/TH17-02-0134
Abstract: Introduction Despite a marked recent increase in the number of publications describing the incidence of venous thromboembolism (VTE) in Asia, and especially in mainland China, Hong Kong, Taiwan, Korea, Japan and Singapore, there remains a lack of consensus on the true risks, and trends over time, to inform appropriate clinical practice. The purpose of this systematic review was therefore to examine evidence about the incidence of symptomatic VTE in Asia. Methods Databases were searched for studies from Asia, published between January 1995 and February 2016, on the incidence of symptomatic VTE, deep vein thrombosis (DVT) or pulmonary embolism. Review of eligible studies was conducted independently by two reviewers. Data were extracted on incidence, predispositions and recurrence of VTE. Results One thousand nighty-five studies were identified, of which 73 were eligible for full text review and data extraction. Three population-wide estimates of VTE rates identified from Korea, Taiwan and Hong Kong reported annual incidences of 13.8, 15.9 and 19.9 per 100,000, respectively. Nine studies of Asian hospital registries or databases reported VTE rates ranging from 11 to 88 cases per 10,000 admissions. Population-based estimates of post-surgical DVT rates ranged from 0.15 to 1.35%. Age was a significant risk factor for VTE in all population groups. Conclusion Population-wide incidence estimates in Asia were approximately 15 to 20% of the levels recorded in western countries but have increased over time. It is anticipated this synthesis of evidence on the incidence of VTE and its predisposing factors will increase awareness about VTE in Asian populations.
Publisher: Wiley
Date: 11-1987
DOI: 10.1111/J.1440-1673.1987.TB01866.X
Abstract: The incidence of cardiovascular and cerebrovascular disease is steadily increasing in South East Asian countries including Indian sub continent. Many lipids, apolipoproteins and Lp (a) except HDL-C and apo A-I, A-II are implicated as risk factors for coronary artery disease and cerebrovascular disease. There is great need to have national guidelines for each country like the ATP III guidelines recommended for U.S. population. For recommending appropriate medical decision limits, it is mandatory that each country establishes reference intervals pertaining to their population due to dietary, genetic and environmental ersity. In the present study, reference intervals for serum lipids, apolipoproteins and Lp (a) were established in a total of 1923 healthy Indian reference in iduals comprising 1161 healthy men and 762 healthy women from Andhra Pradesh. For each analyte viz., serum total cholesterol, HDL-C, LDL-C, triglycerides, Lp (a), Apo A-I, Apo A-II, B, C-II, C-III and E, mean, two SD, median, confidence limits of mean, different percentile values are presented. The study also includes decade wise changes in each analyte and comparison of lipids, lipoproteins and Lp (a) among few populations covering U.S., India, Japan, Sweden, Finland and China. Reference Intervals for all lipid and lipoprotein parameters will immensely help in assessing associated risk for cardiovascular and cerebrovascular diseases in India. Additionally, the results will be beneficial in formulating our own guidelines pertaining to Indian population.
Publisher: Springer Science and Business Media LLC
Date: 1982
DOI: 10.1007/BF00548401
Abstract: Recombination among infectious bronchitis viruses (IBVs), coupled with point mutations, insertions, and deletions that occur in the genome, is thought to contribute to the emergence of new IBV variants. In this study an IBV, ck/CH/LJL/111054, was isolated from a H120-vaccinated chicken, which presented with a suspected IBV infection. Phylogenetic analysis of the S1 subunit sequence confirmed that strain ck/CH/LJL/111054 is of the Connecticut-type however, further extensive full-length genomic analysis identified the occurrence of recombination events. Therefore, strain ck/CH/LJL/111054 may have originated from recombination events between Conn- and Mass-like strains at three recombination breakpoints: two located within the nsp3 gene sequence and one in the nsp12 gene sequence. Further, the uptake of the 5' untranslated regions, nsp2, parts of nsp3, nsp4-11, and parts of nsp 12 from Mass-like virus by ck/CH/LJL/111054 might have resulted in changes in viral replication efficiency rather than antigenic changes, via cross-neutralization analysis with the H120 strain. Recombination events coupled with the accumulation of mutations in the ck/CH/LJL/111054 genome may account for its increased virulence in specific-pathogen free chickens.
Publisher: Wiley
Date: 06-1991
DOI: 10.1111/J.1445-5994.1991.TB04697.X
Abstract: We report a comparison of warfarin treatment outcomes in 172 inpatients in two general hospitals randomly assigned to commence warfarin therapy by one of two methods the first where warfarin dosage was determined using a flexible dose induction protocol, and the other where dosage was prescribed empirically by resident medical staff. The mean INR for each treatment day, the mean time to reach a therapeutic level of INR, the mean maintenance dose and the mean time to reach maintenance dose were not significantly different between the protocol and empirical treatment groups. Although the mean observations of warfarin effect were similar between the two groups, there were more patients with excessive warfarin effect (INR greater than 4.0) during empirical treatment. In addition, age and identified complicating factors such as interfering drugs, heart failure or alcohol abuse were significant predictors of excessive warfarin effect, regardless of treatment group. The protocol dose administered on day 4 of treatment, which has been used as a determinant of maintenance dose, predicted maintenance dose to within 1 mg in 57/83 patients (69%, 95% confidence interval: 59-79%). We conclude that as a method for safely and effectively initiating warfarin therapy, this protocol at least matches the empirical prescribing skills of medical staff in a teaching hospital.
Publisher: Massachusetts Medical Society
Date: 15-02-1990
Publisher: BMJ
Date: 06-1984
DOI: 10.1136/ARD.43.3.402
Abstract: The mechanism of D-penicillamine induced thrombocytopenia in rheumatoid arthritis was investigated by measuring platelet life-span and platelet production rate in 2 groups of rheumatoid arthritis patients treated with 250-750 mg/day D-penicillamine, 14 with a normal platelet count and 9 with thrombocytopenia (platelet count 50-130 X 10(9)/1). Age matched control patients not treated with D-penicillamine included 14 with rheumatoid arthritis and 9 with osteoarthritis. The platelet life-span was normal, but platelet production rate was significantly reduced in the thrombocytopenic patients, suggesting that D-penicillamine causes thrombocytopenia through bone marrow suppression.
Publisher: Springer Science and Business Media LLC
Date: 1982
DOI: 10.1007/BF00548400
Publisher: AMPCo
Date: 1970
DOI: 10.5694/J.1326-5377.1970.TB77688.X
Abstract: Magnetic nanoparticles (MNPs) functionalized with targeting moieties can recognize specific cell components and induce mechanical actuation under magnetic field. Their size is adequate for reaching tumors and targeting cancer cells. However, due to the nanometric size, the force generated by MNPs is smaller than the force required for largely disrupting key components of cells. Here, we show the magnetic assembly process of the nanoparticles inside the cells, to form elongated aggregates with the size required to produce elevated mechanical forces. We synthesized iron oxide nanoparticles doped with zinc, to obtain high magnetization, and functionalized with the epidermal growth factor (EGF) peptide for targeting cancer cells. Under a low frequency rotating magnetic field at 15 Hz and 40 mT, the internalized EGF-MNPs formed elongated aggregates and generated hundreds of pN to dramatically damage the plasma and lysosomal membranes. The physical disruption, including leakage of lysosomal hydrolases into the cytosol, led to programmed cell death and necrosis. Our work provides a novel strategy of designing magnetic nanomedicines for mechanical destruction of cancer cells.
Publisher: American College of Physicians
Date: 15-04-2014
Publisher: Georg Thieme Verlag KG
Date: 2010
DOI: 10.1160/TH09-12-0870
Abstract: Standard treatment with heparin followed by vitamin K antagonists is frequently complicated by bleeding and recurrent venous thromboembolism (VTE) in cancer patients with VTE. To compare the efficacy, safety and overall survival of long-term idraparinux treatment to standard therapy in cancer patients we conducted a post-hoc analysis in the subgroup of non-active and active cancer patients included in the Van Gogh DVT clinical trial. The cancer patients with deep venous thrombosis (DVT) and without pulmonary embolism (PE) were randomised to standard treatment or a once-weekly subcutaneous injection of idraparinux (2.5 mg), a synthetic pentasaccharide. 421 cancer patients were included. A total of 220 patients received idraparinux and 201 were allocated to standard therapy for three months (8%) or six months (92%). A recurrent VTE was observed during the first six months in 2.5% (n=5) of the idraparinux recipients compared to 6.4% (n=12) in the standard therapy group (hazard ratio 0.39, 95% confidence interval [CI] 0.14–1.11). The rate of bleeding was comparable (odds ratio 0.89, 95% CI 0.50–1.59). The outcomes were similar at three months after randomisation in all patients. Of the idraparinux recipients, 22.7% (n=50) died during the study period compared to 48 patients (23.9%) in the standard treatment group (hazard ratio 0.99, 95% CI 0.66–1.48). In conclusion, no significant safety or survival differences were observed between cancer patients with DVT treated with idraparinux for six months compared to standard therapy. Fewer recurrent VTEs were observed in the idraparinux group however, this was not statistically significant and also because of study limitations this should be interpreted with caution.
Publisher: Georg Thieme Verlag KG
Date: 10-10-2014
Abstract: Thrombosis is a common pathology underlying ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). The Global Burden of Disease Study 2010 (GBD 2010) documented that ischemic heart disease and stroke collectively caused one in four deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability. We performed a systematic review of the literature on the global disease burden due to VTE in low-, middle-, and high-income countries. Studies from Western Europe, North America, Australia, and Southern Latin America (Argentina) yielded consistent results with annual incidences ranging from 0.75 to 2.69 per 1,000 in iduals in the population. The incidence increased to between 2 and 7 per 1,000 among those 70 years of age or more. Although the incidence is lower in in iduals of Chinese and Korean ethnicity, their disease burden is not low because of population aging. VTE associated with hospitalization was the leading cause of disability-adjusted-life-years (DALYs) lost in low- and middle-income countries, and second in high-income countries, responsible for more DALYs lost than nosocomial pneumonia, catheter-related blood stream infections, and adverse drug events. VTE causes a major burden of disease across low-, middle-, and high-income countries. More detailed data on the global burden of VTE should be obtained to inform policy and resource allocation in health systems, and to evaluate if improved utilization of preventive measures will reduce the burden.
Publisher: Georg Thieme Verlag KG
Date: 1998
Abstract: Two clinical trials in patients with acute deep venous thrombosis have indicated that the outpatient management with fixed-dose, subcutaneous low-molecular-weight heparin is at least as effective and safe as inpatient treatment with unfractionated intravenous heparin with respect to recurrent venous thromboembolism and major bleeding. We performed an economic evaluation alongside one of these trials to assess the cost consequences of the outpatient management strategy. Data were collected through case record forms, complemented by a prospective questionnaire in 78 consecutive patients, interviews with health care providers, and hospital data bases. Our study demonstrated that seventy-five percent of patients allocated to low-molecular-weight heparin received treatment either entirely at home or after a brief hospital stay. Fifteen percent of these patients required professional domiciliary care. Within-centre comparisons of resource utilisation in terms of natural units showed that outpatient management with low-molecular-weight heparin reduced the average number of hospital days in the initial treatment period in nine centres by 59 percent (95% CI: 43 to 71 percent) accompanied by a limited increase in outpatient and professional domiciliary care. The average reduction in hospital days at the end of follow up was 40 percent (95% CI: 25 to 54 percent). A cost-minimisation analysis, focusing on resource utilisation directly related to the treatment of deep venous thrombosis and associated costs in one centre demonstrated a cost reduction of 64 percent (95% CI: 56 to 72 percent) with the outpatient management with low-molecular-weight heparin. These data suggest that outpatient management of patients with proximal venous thrombosis using low-molecular-weight heparin reduces resource utilisation and total treatment cost. Implementation should be preceded by a cautious evaluation of a potential cost shifting and organisational prerequisites.
Publisher: American College of Physicians
Date: 09-2015
Publisher: Wiley
Date: 06-1993
DOI: 10.1111/J.1445-5994.1993.TB01735.X
Abstract: Colorectal cancer (CRC) is one of the most common gastrointestinal tumors, which accounts for approximately 10% of all diagnosed cancers and cancer deaths worldwide per year. We adopted active constituent prescreening, target predicting, protein-protein interaction (PPI) analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, differentially expressed gene analysis, and molecular docking to establish a system pharmacology database of SBH against CRC. A total of 64 active constituents of SBH were obtained and 377 targets were predicted, and the result indicated that quercetin, luteolin, wogonin, and apigenin were the main active constituents of SBH. Glucocorticoid receptor (NR3C1), pPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA), cellular tumor antigen p53 (TP53), transcription factor AP-1 (JUN), mitogen-activated protein kinase 1 (MAPK1), Myc protooncogene protein (MYC), cyclin-dependent kinase 1 (CDK1), and broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) were the major targets of SBH in the treatment of CRC. GO analysis illustrated that the core biological process regulated by SBH was the regulation of the cell cycle. Thirty pathways were presented and 8 pathways related to CRC were involved. Molecular docking presented the binding details of 3 key targets with 6 active constituents. The mechanisms of SBH against CRC depend on the synergistic effect of multiple active constituents, multiple targets, and multiple pathways.
Publisher: Massachusetts Medical Society
Date: 22-11-2012
Publisher: Massachusetts Medical Society
Date: 20-09-2018
Publisher: American College of Physicians
Date: 20-06-2017
Publisher: Massachusetts Medical Society
Date: 13-09-2007
DOI: 10.1056/NEJMOA064247
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2008
Publisher: Springer Science and Business Media LLC
Date: 12-1979
DOI: 10.2165/00003495-197918060-00002
Abstract: Because platelets are so important in thrombus formation, drugs which inhibit platelet function (the 'antiplatelet drugs') have considerable potential as antithrombotic agents. Among the antiplatelet drugs, only aspirin, sulphinpyrazone, dipyridamole, hydroxychloroquine, and clofibrate have had wide clinical trial. Their effects on platelet metabolism differ. Aspirin prevents platelet prostaglandin synthesis by acetylating and irreversibly inactivating platelet prostaglandin synthetase, while sulphinpyrazone is a reversible inhibitor of the same enzyme. Both aspirin and sulphinpyrazone impair the platelet release reaction and reduce platelet aggregation, but neither prevents platelet adhesion to the subendothelium or to foreign surfaces. On the other hand, dipyridamole reduces platelet adhesion as well as aggregation, probably by inhibiting phosphodiesterase and so raising platelet cyclic AMP levels. The effects of hydroxychloroquine and clofibrate have been less well defined. As the antiplatelet drugs form a erse group of substances with differing effects on platelet function, it is hardly surprising that every potential clinical application of each antiplatelet drug or drug combination has had to be tested separately, and that these drugs have not proved to be equally effective. One or more antiplatelet drugs have now been evaluated in each of the following situations.
Publisher: Massachusetts Medical Society
Date: 26-07-2001
Publisher: Massachusetts Medical Society
Date: 29-08-2013
Publisher: Elsevier BV
Date: 10-1989
Publisher: Therapeutic Guidelines Limited
Date: 08-1998
Publisher: Massachusetts Medical Society
Date: 13-09-1990
Publisher: Georg Thieme Verlag KG
Date: 04-1989
Abstract: F18-fimbriated Escherichia coli are associated with porcine postweaning diarrhea and edema disease. Adhesion of F18-fimbriated bacteria to the small intestine of susceptible pigs is mediated by the minor fimbrial subunit FedF. However, the target cell receptor for FedF has remained unidentified. Here we report that F18-fimbriated E. coli selectively interact with glycosphingolipids having blood group ABH determinants on type 1 core, and blood group A type 4 heptaglycosylceramide. The minimal binding epitope was identified as the blood group H type 1 determinant (Fucalpha2Galbeta3GlcNAc), while an optimal binding epitope was created by addition of the terminal alpha3-linked galactose or N-acetylgalactosamine of the blood group B type 1 determinant (Galalpha3(Fucalpha2)Galbeta3GlcNAc) and the blood group A type 1 determinant (GalNAcalpha3(Fucalpha2)-Galbeta3GlcNAc). To assess the role of glycosphingolipid recognition by F18-fimbriated E. coli in target tissue adherence, F18-binding glycosphingolipids were isolated from the small intestinal epithelium of blood group O and A pigs and characterized by mass spectrometry and proton NMR. The only glycosphingolipid with F18-binding activity of the blood group O pig was an H type 1 pentaglycosylceramide (Fucalpha2Galbeta3GlcNAc-beta3Galbeta4Glcbeta1Cer). In contrast, the blood group A pig had a number of F18-binding glycosphingolipids, characterized as A type 1 hexaglycosylceramide (GalNAcalpha3(Fucalpha2)Galbeta3GlcNAcbeta3Galbeta4Glcbeta1Cer), A type 4 heptaglycosylceramide (GalNAcalpha3(Fucalpha2)Galbeta3GalNAcbeta3Galalpha4Galbeta4Glcbeta1Cer), A type 1 octaglycosylceramide (GalNAcalpha3(Fucalpha2)Galbeta3GlcNAcbeta3Galbeta3GlcNAcbeta3Galbeta4Glcbeta1Cer), and repetitive A type 1 nonaglycosylceramide (GalNAcalpha3(Fucalpha2)Galbeta3GalNAcalpha3-(Fucalpha2)Galbeta3GlcNAcbeta3Galbeta4Glcbeta1Cer). No blood group antigen-carrying glycosphingolipids were recognized by a mutant E. coli strain with deletion of the FedF adhesin, demonstrating that FedF is the structural element mediating binding of F18-fimbriated bacteria to blood group ABH determinants.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-1976
Abstract: The response to a standard dose of heparin was studied in 20 patients with venous thromboembolism. The heparin regimen consisted of intravenous injection of 70 units per kg, followed after 90 minutes by a maintenance dose of 400 units per kg per 24 hours given by continuous infusion. Plasma heparin activity and the activated partial thromboplastin time (APTT) were measured at intervals to determine clearance of the initial injection and the response to maintenance dose. Large inter-in idual variations were found in the anticoagulant effect and these were due in part to differences in heparin clearance and in part to differences in the APTT response to given amounts of heparin (heparin effect index). The heparin half-life was 63 +/- 15 minutes when plasma heparin activities were used for this calculation and 84 +/- 71.5 minutes when the APTT was used. These results are similar to values previously reported in normal volunteers. Four of the 20 patients had pulmonary embolism and in these heparin half-life was significantly shortened (P less than 0.005).
Publisher: Wiley
Date: 06-1972
DOI: 10.1111/J.1365-2141.1972.TB05720.X
Abstract: The association between infant formula feeding at birth and subsequent feeding patterns in a low- or middle-income context is not clear. We examined the association of infant formula feeding during the first 3 d after birth with subsequent infant formula feeding and early breastfeeding cessation in Vietnam. In a cross-sectional survey, we interviewed 10,681 mothers with children aged 0-23 mo (mean age: 8.2 mo 52% boys) about their feeding practices during the first 3 d after birth and on the previous day. We used stratified analysis, multiple logistic regression, propensity score-matching analysis, and structural equation modeling to minimize the limitation of the cross-sectional design and to ensure the consistency of the findings. Infant formula feeding during the first 3 d after birth (50%) was associated with a higher prevalence of subsequent infant formula feeding [stratified analysis: 7-28% higher (nonoverlapping 95% CIs for most comparisons) propensity score-matching analysis: 13% higher (P < 0.001) multiple logistic regression: OR: 1.47 (95% CI: 1.30, 1.67)]. This practice was also associated with a higher prevalence of early breastfeeding cessation (e.g., <24 mo) [propensity score-matching analysis: 2% (P = 0.08) OR: 1.33 (95% CI: 1.12, 1.59)]. Structural equation modeling showed that infant formula feeding during the first 3 d after birth was associated with a higher prevalence of subsequent infant formula feeding (β: 0.244 P < 0.001), which in turn was linked to early breastfeeding cessation (β: 0.285 P < 0.001). Infant formula feeding during the first 3 d after birth was associated with increased subsequent infant formula feeding and the early cessation of breastfeeding, which underscores the need to make early, exclusive breastfeeding normative and to create environments that support it.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-11-2000
DOI: 10.1161/01.CIR.102.22.2726
Abstract: Background —Patients with venous thromboembolism require initial treatment with an immediate-acting anticoagulant, low-molecular-weight heparin. We evaluated a novel synthetic factor Xa inhibitor (SR90107a/ORG31540) as an alternative treatment. Methods and Results —A randomized-parallel-group, phase II trial to assess the efficacy and safety of SR90107a/ORG31540 (5, 7.5, or 10 mg once daily) relative to low-molecular-weight heparin (dalteparin, 100 IU/kg twice daily) in symptomatic proximal deep vein thrombosis. The primary outcome measure was the change in thrombus mass, assessed by ultrasonography of the leg veins and perfusion lung scintigraphy, performed at baseline and day 7±1. A positive outcome was defined as improvement of the ultrasound and/or perfusion scan result without deterioration of either test. Other outcome measures included symptomatic, recurrent venous thromboembolism and major bleeding for a period of 3 months. All outcomes were interpreted with the observer unaware of treatment allocation. A positive primary outcome was observed in 46 of 100 (46%), 52 of 108 (48%), 48 of 115 (42%), and 56 of 115 (49%), respectively, of the subjects given 5, 7.5, or 10 mg SR90107a/ORG31540 or dalteparin. There were 8 recurrent thromboembolic complications (2.4%) in the 334 patients treated with SR90107a/ORG31540 and 6 (5.0%) in the 119 dalteparin patients, a difference of 2.6% in favor of SR90107a/ORG31540 (95% CI −2.1% to 10.1%). The incidence of bleeding was low and was similar among the groups. Conclusions —The factor Xa inhibitor SR90107a/ORG31540 appears to be an effective and safe treatment for patients with deep vein thrombosis across a wide range of doses. This synthetic compound merits evaluation in phase III studies.
Publisher: British Editorial Society of Bone & Joint Surgery
Date: 02-2012
DOI: 10.1302/0301-620X.94B2.27850
Abstract: In order to compare the effect of oral apixaban (a factor Xa inhibitor) with subcutaneous enoxaparin on major venous thromboembolism and major and non-major clinically relevant bleeding after total knee and hip replacement, we conducted a pooled analysis of two previously reported double-blind randomised studies involving 8464 patients. One group received apixaban 2.5 mg twice daily (plus placebo injection) starting 12 to 24 hours after operation, and the other received enoxaparin subcutaneously once daily (and placebo tablets) starting 12 hours (± 3) pre-operatively. Each regimen was continued for 12 days (± 2) after knee and 35 days (± 3) after hip arthroplasty. All outcomes were centrally adjudicated. Major venous thromboembolism occurred in 23 of 3394 (0.7%) evaluable apixaban patients and in 51 of 3394 (1.5%) evaluable enoxaparin patients (risk difference, apixaban minus enoxaparin, -0.8% (95% confidence interval (CI) -1.2 to -0.3) two-sided p = 0.001 for superiority). Major bleeding occurred in 31 of 4174 (0.7%) apixaban patients and 32 of 4167 (0.8%) enoxaparin patients (risk difference -0.02% (95% CI -0.4 to 0.4)). Combined major and clinically relevant non-major bleeding occurred in 182 (4.4%) apixaban patients and 206 (4.9%) enoxaparin patients (risk difference -0.6% (95% CI -1.5 to 0.3)). Apixaban 2.5 mg twice daily is more effective than enoxaparin 40 mg once daily without increased bleeding.
Publisher: Elsevier BV
Date: 10-0002
DOI: 10.1016/S0140-6736(73)90855-6
Abstract: Antiretroviral therapy has revolutionized the course of HIV infection, improving immune function and decreasing dramatically the mortality and morbidity due to the opportunistic complications of the disease. Nonetheless, even with sustained suppression of HIV replication, many HIV-infected persons experience a syndrome characterized by increased T cell activation and evidence of heightened inflammation and coagulation. This residual immune dysregulation syndrome or RIDS is more common in persons who fail to increase circulating CD4+ T cells to normal levels and in several epidemiologic studies it has been associated with increased morbidity and mortality. These morbid and fatal events are not the typical opportunistic infections and malignancies seen in the early AIDS era but rather comprise a spectrum of cardiovascular events, liver disease, metabolic disorders, kidney disease, bone disease, and a spectrum of malignant complications distinguishable from the opportunistic malignancies that characterized the earlier days of the AIDS epidemic. While immune activation, inflammation, and coagulopathy are characteristic of untreated HIV infection and improve with drug-induced control of HIV replication, the drivers of RIDS in treated HIV infection are incompletely understood. And while inflammation, immune activation, and coagulopathy are more common in treated persons who fail to restore circulating CD4+ T cells, it is not entirely clear how these two phenomena are linked.
Publisher: Georg Thieme Verlag KG
Date: 2006
DOI: 10.1160/TH05-07-0489
Abstract: Clinical outcomes of 1,478 danaparoid treatment case reports for HIT (involving 1,418 patients) treated between 1982 and mid-2004 are analysed. Treatment in 1,291 episodes was for current HIT. Thromboembolism due to HIT was present in 39.4a%. The patients include 33 children and 32 pregnancies. Two hundred twenty-six patients required extra-corporeal circuit use for renal failure, 241 patients had a concomitant thrombophilic disorder, and 351 major operations were performed. Clinical outcomes were assessed during danaparoid treatment (range one day to 3.5 years) plus three months of follow-up. Of the danaparoid-treated patients 83.8a% survived 63.7a% had no or minor adverse events and 20.1a% suffered serious non-fatal adverse events. New thromboses occurred during 9.7a% of treatment episodes, and 16.4a% of treatment episodes had an inadequate treatment response (i. e. developed one or more of the following: new/extended thrombosis, persistent/new platelet count reduction, unplanned utation during treatment and follow-up). Major bleeding was reported in 8.1a% of treatment episodes. Clinical cross-reactivity of danaparoid (new ersistent platelet count reduction and/or new/extended thrombosis) was confirmed serologically in 23 of 36 patients with positive pretreatment serological danaparoid cross-reactivity and in 22 of 32 additional patients tested at the time of the new event, i. e. a total of 45 patients (3.2a%). Clinical outcomes of these case reports of patients given danaparoid because of suspected or confirmed HIT appear to be comparable with those reported by others who used direct thrombin inhibitors, especially when a sufficient danaparoid dosing intensity was used in patients with isolated HIT. Post-operative bleeding limits danaparoid use for cardiopulmonary by-pass surgery. Routine clinical and platelet count monitoring are required to minimise adverse reactions due to cross-reactivity.
Publisher: American Medical Association (AMA)
Date: 09-1975
Publisher: Elsevier BV
Date: 02-1970
DOI: 10.1016/S0140-6736(70)90636-7
Abstract: Detection of pathogens from environmental s les is often h ered by sensors interacting with environmental particles such as soot, pollen, or environmental dust such as soil or clay. These particles may be of similar size to the target bacterium, preventing removal by filtration, but may non-specifically bind to sensor surfaces, fouling them and causing artefactual results. In this paper, we report the selective manipulation of soil particles using an AC electrokinetic microfluidic system. Four heterogeneous soil s les (smectic clay, kaolinitic clay, peaty loam, and sandy loam) were characterised using dielectrophoresis to identify the electrical difference to a target organism. A flow-cell device was then constructed to evaluate dielectrophoretic separation of bacteria and clay in a continous flow through mode. The average separation efficiency of the system across all soil types was found to be 68.7% with a maximal separation efficiency for kaolinitic clay at 87.6%. This represents the first attempt to separate soil particles from bacteria using dielectrophoresis and indicate that the technique shows significant promise with appropriate system optimisation, we believe that this preliminary study represents an opportunity to develop a simple yet highly effective s le processing system.
Publisher: Elsevier BV
Date: 02-2012
Publisher: Therapeutic Guidelines Limited
Date: 04-2010
Publisher: Georg Thieme Verlag KG
Date: 1993
Abstract: This double-blind, randomised, multicentre trial in 513 patients having elective surgery for intra-abdominal or intrathoracic malignancy compared the efficacy and safety of venous thrombosis (VT) prophylaxis using 750 anti-factor Xa units of Orgaran (a mixture of low molecular weight heparinoids) given subcutaneously (sc) twice-daily with that of twice-daily injections of 5,000 units Standard heparin. The main study endpoints were the development of postoperative VT detected by 125I-fibrinogen leg scanning, and the onset of clinically significant venous thromboembolism or bleeding. “Intent to treat” analysis showed a statistically non-significant trend towards less VT during Orgaran prophylaxis (10.4%) than after heparin (14.9%) and there was no difference in bleeding complications between the two study groups. Results remained similar if only patients who completed the intended course of therapy (“compliant patients”) were analysed. Other trials have shown that Orgaran prevents VT after hip surgery and stroke. We now show it is also safe and effective in patients having major surgery for cancer.
Publisher: Elsevier BV
Date: 1968
DOI: 10.1016/S0140-6736(68)90068-8
Abstract: To evaluate sleep quality in relation to lifestyle characteristics including consumption of energy drinks and other caffeinated beverages among Peruvian college students. A total of 2,458 college students were invited to complete a self-administered questionnaire that collected information about a variety of behaviors including consumption of energy drinks, caffeinated and alcoholic beverages. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Logistic regression procedures were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for poor sleep quality in relation to lifestyle characteristics. A total of 965 males and 1,493 female students were enrolled in the study. 52.0% of males and 58.4% of females experienced poor sleep quality (p=0.002). Females (OR=1.28 95% CI 1.08-1.51) and those who reported consuming ≥ 3 stimulant beverages per week (OR=1.88 95% CI 1.42-2.50) had higher odds of poor sleep quality. Students who consumed 1-19 alcoholic beverages monthly (OR=1.90 95% CI 1.46-2.49) had a higher odds of long sleep latency. Consumption of ≥ 3 stimulant beverages per week was associated with daytime dysfunction due to sleep loss (OR=1.45 95% CI 1.10-1.90), short sleep duration (OR= 1.49 95% CI 1.14-1.94), and use of sleep medication (OR= 2.10 95% CI 1.35-3.28). Consumption of energy drinks, other caffeinated beverages and alcoholic beverages are risk factors of poor sleep quality. Increased awareness of these associations should promote interventions to improve students' lifestyle habits, including consumption of alcoholic and caffeinated beverages, and overall health.
Publisher: American College of Physicians
Date: 21-08-2018
Publisher: Wiley
Date: 11-1970
DOI: 10.1111/IMJ.1970.19.4.334
Abstract: We have investigated the physiology and mechanical profiles of skinned papillary muscle fibers from transgenic mice expressing the N47K mutation in the myosin regulatory light chain (RLC), shown to cause hypertrophic cardiomyopathy in humans. The results were compared with wild-type (WT) mice, both expressing the human ventricular RLC. Rate constants of a cross-bridge (XB) cycle were deduced from tension transients induced by sinusoidal length changes during maximal Ca
Publisher: American College of Physicians
Date: 16-11-2010
Publisher: American College of Physicians
Date: 20-12-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2002
DOI: 10.1097/00062752-200209000-00006
Abstract: Fondaparinux (a synthetic heparin analogue) (Sanofi-Synthelabo Paris, France and Organon Research Oss, The Netherlands) is the subject of intense recent clinical evaluation for the prevention and treatment of venous and arterial thromboembolism. The drug replicates the sulphated antithrombin-binding pentasaccharide sequence in heparin and induces potent and specific antithrombin-mediated anti-Xa activity with excellent bioavailability and a long circulating half-life of 18 hours that makes it ideal for once-daily subcutaneous dosing. Its very short chain length ensures this heparin pentasaccharide (PS) is devoid of anti-factor IIa activity. No need for laboratory monitoring is anticipated. Fondaparinux does not cross-react ex vivo with the anti-platelet antibodies responsible for heparin-induced thrombocytopenia. Fondaparinux was evaluated in four large, randomized, placebo-controlled, double-blind phase III trials of deep vein thrombosis prevention after major joint surgery where the PS given after surgery was compared with a low molecular weight heparin (LMWH). LMWH was started before surgery in two comparisons and soon after surgery in the others. The trials shared the same blindly adjudicated efficacy and safety endpoints: efficacy was measured by recording subclinical deep vein thrombosis detected by screening with bilateral venography, plus clinically suspected and confirmed symptomatic thrombosis and embolism safety was indicated by the rate of major bleeding. Bleeding was considered major if it caused death or reoperation, affected an internal organ, or was overt and associated with a bleeding index of 2 or more. By comparison with LMWH, 2.5 mg/d of the PS beginning 4 to 8 hours after wound closure reduced venous thromboembolism rates by 56% and 26% after elective hip replacement, 63% after knee replacement, and 62% after hip fracture surgery. In three studies and overall, the effect was statistically very significant and included similarly reduced rates of proximal deep vein thrombosis. In absolute terms, the DVT rates with PS are the lowest yet seen after major joint surgery. Trends toward more major bleeding with PS in three studies were statistically significant in one trial. PS did not increase risks from reoperation, internal bleeding, or death because of bleeding, because between-group differences were caused entirely by an excess of patients with a raised bleeding index. Post hoc analysis suggests this excess can be explained by too-early postoperative drug administration and may be avoided without loss of efficacy by giving the first PS injection 6 to 8 hours after surgery. Results of phase III treatment trials for DVT/PE will soon be available, but studies in coronary artery disease are less advanced.
Publisher: Oxford University Press (OUP)
Date: 1983
Abstract: The effect of preventive intermittent calf compression on the incidence, distribution and extent of venous thrombosis after elective hip replacement was examined by randomized trial in 90 patients who were screened for postoperative thrombosis with 125I-fibrinogen leg scanning and impedance plethysmography, followed by routine venography on the seventh postoperative day. Venography showed that leg compression reduced the incidence of calf vein thrombosis from 45 per cent (21/47) in untreated patients to 16 per cent (7/43) (P & 0·005), but not that of proximal (i.e. popliteal or femoral) vein thrombosis, which occurred in 23 per cent of treated and 26 per cent of untreated patients. However, proximal vein thrombosis appeared to be less extensive in treated patients. Proximal vein thrombosis was found in 40 per cent of patients who had hip replacement by a modified Charnley technique (17/43 patients), and 9 per cent of patients in whom a posterior surgical approach was used (4/43 patients) (P & 0·005), strongly suggesting that surgical technique may influence the proximal vein thrombosis rate after elective hip replacement.
Publisher: AMPCo
Date: 09-2001
DOI: 10.5694/J.1326-5377.2001.TB143561.X
Abstract: For the management of acute thrombotic events in pregnancy therapeutic doses of low molecular weight heparins (LMWH) may be used, unless the shorter half-life of intravenous unfractionated heparin (UH) and predictable reversibility by protamine are important. Treatment should be continued up until delivery and into the puerperium. Pregnant women who have had an acute thrombotic event should be delivered by a specialist team. In the case of recent thrombosis, delivery should be planned and the time during which anticoagulation therapy is ceased around the time of delivery should be minimised. Therapeutic doses of LMWH contraindicate the use of regional anaesthesia, and a switch to intravenous UH before delivery may allow greater flexibility in this regard. Prophylactic doses of LMWH can be used to reduce the risk of recurrent thromboembolic events in pregnancy. The regimen used will depend on the previous history, the family history and the presence of risk factors, including the genetic and acquired causes of thrombophilia. Women with mechanical heart valves are at high risk during pregnancy and require therapeutic anticoagulation throughout pregnancy under the direction of experienced specialists. Low-dose aspirin can reduce the risk of recurrent pre-ecl sia by about 15%, but the role of UH and LMWH in the prevention of recurrent miscarriage or obstetric complications associated with uteroplacental insufficiency is still uncertain.
Publisher: Walter de Gruyter GmbH
Date: 04-12-2007
Abstract: Zugleich Besprechung von: Ingrid Gilcher-Holtey (Hrsg.), Zwischen den Fronten. Positionskämpfe europäischer Intellektueller im 20. Jahrhundert Lutz Raphael/Heinz-Elmar Tenorth (Hrsg.), Ideen als gesellschaftliche Gestaltungskraft im Europa der Neuzeit. Beiträge für eine erneuerte Geistesgeschichte
Publisher: Wiley
Date: 06-1989
DOI: 10.1111/J.1445-5994.1989.TB00243.X
Abstract: We have evaluated a flexible warfarin dose induction protocol by monitoring its performance in 100 elderly inpatients. The protocol (designed by Fennerty et al., has two aims: (a) to move the prothrombin time (PT) ratio smoothly and quickly into its therapeutic range, and (b) to predict the steady-state warfarin requirement from the PT ratio measured on the fourth treatment day. It proved simple to use and reasonably successful, since after four days, 67/100 patients had achieved a therapeutic level of PT ratio, nine exceeded the therapeutic range, and 24 remained sub-therapeutic, while none had bled due to excessive anticoagulation. Maintenance dose prediction was tested by comparing the predicted and observed maintenance doses in patients within the 'therapeutic range' of PT ratio after various median times of treatment. After ten days, the observed dose was within 1 mg of that predicted in 65/86 patients (76%). This proportion became 57/77 (74%) after 18 days, and 49/79 (62%) after 34 days.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-1976
Abstract: Impedance plethysmography using the cuff technique has been compared with venography in 346 consecutive patients with suspected venous thromboembolism. The limbs were classified according to the venographic results as no thrombosis, proximal (popliteal, femoral, or iliac) vein thrombosis, and calf thrombosis. A discriminant analysis was performed. The impedance plethysmographic result was normal in 386 of 397 limbs which were normal on venography, a specificity of 97%, and abnormal in 124 of 133 limbs which showed proximal vein thrombosis, a sensitivity of 93%. Seventy-three of 88 limbs with calf vein thrombi and a normal impedance plethysmographic result. The sensitivity in 29 limbs with asymptomatic proximal vein thrombosis was 83%. Impedance plethysmography is an accurate method for detecting proximal vein thrombosis but has limitations which include the possibility of false positive results due to arterial insufficiency and muscle tension.
Publisher: Massachusetts Medical Society
Date: 05-1975
Publisher: Massachusetts Medical Society
Date: 19-11-2009
DOI: 10.1056/NEJMC091473
Publisher: Springer Science and Business Media LLC
Date: 1976
DOI: 10.2165/00003495-197612020-00002
Abstract: The defibrinating agent ancrod has had limited clinical trial, but appears to give no advantages over heparin. Intravenous infusion of dextran, a glucose polymer, has been shown to have an antithrombotic effect in many experimental models of thrombosis. However, the evidence that dextran is a clinically valuable antithrombotic drug is conflicting. A number of controlled randomized studies have shown that dextran can prevent postoperative venous thromboembolism when a large volume of dextran 40 or 70 was infused rapidly during and after surgery. However, blood volume expansion during dextran treatment prohibits its use in patients with reduced cardiac reserve, and infrequent though sometimes severe, allergic reactions have been reported. Evidence that dextran is of value for the treatment of venous or arterial thromboembolism comes from uncontrolled studies and is not convincing. Many compounds have been shown to inhibit platelet function in vitro but only five of these drugs have been extensively evaluated as prophylactic or therapeutic antithrombotic agents in man. These are aspirin, sulphinpyrazone, dipyridamole, hydroxychloroquine and clofibrate. They have been evaluated mainly in patients with cerebral vascular disorders, coronary artery disease, peripheral artery ischaemia, venous thromboembolism, prosthetic heart valves, and in patients with arteriovenous shunts. The evaluation of the clinical effect of the platelet function suppressing drugs is in its early stages, but they appear to differ from each other in the spectrum of their clinical effectiveness, and they may be more effective in arterial than in venous thromboembolic disorders. Their role in the management of cerebral vascular disease and coronary artery disease is still uncertain, and should be clarified by the results of a number of multi-centre, prospective, randomized studies which are currently in progress. Three types of thrombolytic drugs have been evaluated clinically the plasminogen activators streptokinase and urokinase, proteolytic enzymes such as plasmin, and agents which increase the level of endogenous plasminogen activator (e.g. anabolic steroids). Of these, the plasminogen activators now have a definite place in clinical practice. The plasminogen activators accelerate the lysis of recent venous thrombi and pulmonary emboli, and of arterial thrombi or emboli. Thrombolytic therapy with these agents should be considered particularly in patients with recent major pulmonary embolism, as lysis of recent emboli is rapid and substantial. It should also be considered in patients with recent extensive venous thrombosis, because total lysis of venous thrombi has been reported to result in long-term preservation of valve function, and is likely to prevent postphlebitic syndrome, though this has not been proven. However, plasminogen activator therapy carries a higher risk of bleeding than heparin treatment...
Publisher: Wiley
Date: 08-2016
DOI: 10.1111/IMJ.13153
Publisher: Wiley
Date: 11-2014
DOI: 10.1111/IMJ.12583
Publisher: Massachusetts Medical Society
Date: 30-10-2003
DOI: 10.1056/NEJMOA035451
Publisher: Massachusetts Medical Society
Date: 15-03-1973
Publisher: AMPCo
Date: 03-2001
Publisher: Massachusetts Medical Society
Date: 07-06-1973
Publisher: AMPCo
Date: 11-2004
DOI: 10.5694/J.1326-5377.2004.TB06407.X
Abstract: For most warfarin indications, the target maintenance international normalised ratio (INR) is 2-3. Risk factors for bleeding complications with warfarin use include age, history of past bleeding and specific comorbid conditions. To reverse the effects of warfarin, vitamin K(1) can be given. Immediate reversal is achieved with a prothrombin complex concentrate (PCC) and fresh frozen plasma (FFP). Vitamin K(1) is essential for sustaining the reversal achieved by PCC and FFP. When oral vitamin K(1) is used for warfarin reversal, the injectable formulation of vitamin K(1) is preferable to tablets because of its flexible dosing this formulation can be given orally or injected. To temporarily reverse the effect of warfarin when there is a need to continue warfarin therapy, vitamin K(1) should be given in a dose that will quickly lower the INR to a safe, but not subtherapeutic, range and will not cause resistance once warfarin is reinstated. Prothrombinex-HT is the only PCC approved in Australia and New Zealand for warfarin reversal. It contains factors II, IX and X, and low levels of factor VII. FFP should be added to Prothrombinex-HT as a source of factor VII when used for warfarin reversal. Simple dental or dermatological procedures may not require interruption to warfarin therapy. If necessary, warfarin therapy can be withheld 5 days before elective surgery, when the INR usually falls to below 1.5 and surgery can be conducted safely. Bridging anticoagulation therapy for patients at high risk for thromboembolism should be undertaken in consultation with the relevant experts.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-07-2007
DOI: 10.1161/CIRCULATIONAHA.106.668020
Abstract: Background— An effective and safe oral anticoagulant that needs no monitoring for dose adjustment is urgently needed for the treatment of diseases that require long-term anticoagulation. Rivaroxaban (BAY 59-7939) is an oral direct factor Xa inhibitor currently under clinical development. Methods and Results— This randomized, parallel-group phase II trial in patients with proximal deep-vein thrombosis explored the efficacy and safety of rivaroxaban 10, 20, or 30 mg BID or 40 mg once daily compared with enoxaparin 1 mg/kg BID followed by vitamin K antagonist. Each treatment was administered for 12 weeks. The primary efficacy end point was an improvement in thrombotic burden at day 21 (assessed by quantitative compression ultrasonography ≥4-point improvement in thrombus score) without recurrent symptomatic venous thromboembolism or venous thromboembolism-related death. The primary safety end point was major bleeding during 12 weeks of treatment. Outcomes were adjudicated centrally without knowledge of treatment allocation. The primary efficacy end point was achieved in 53 (53.0%) of 100, 58 (59.2%) of 98, 62 (56.9%) of 109, and 49 (43.8%) of 112 patients receiving rivaroxaban 10, 20, or 30 mg BID or 40 mg once daily, respectively, compared with 50 (45.9%) of 109 patients treated with enoxaparin/vitamin K antagonist. There was no significant trend in the dose-response relationship between rivaroxaban BID and the primary efficacy end point ( P =0.67). Major bleeding was observed in 1.7%, 1.7%, 3.3%, and 1.7% of patients receiving rivaroxaban 10, 20, or 30 mg BID or 40 mg once daily, respectively. There were no major bleeding events with enoxaparin/vitamin K antagonist. Conclusions— Results of this proof-of-concept and dose-finding study support phase III evaluation of the orally active direct factor Xa inhibitor rivaroxaban, because efficacy and safety were apparent in the treatment of proximal deep-vein thrombosis across a 3-fold range of fixed daily dosing.
Publisher: Informa Healthcare
Date: 2008
Publisher: Wiley
Date: 02-1987
DOI: 10.1111/J.1445-5994.1987.TB05059.X
Abstract: Toll-like receptor 4 (TLR-4) activation after sterile injury leads to organ dysfunction at distant sites. We have shown previously that intestinal barrier breakdown and alteration of tight junction proteins follows thermal injury however, the role of TLR-4 in this process remains unclear. We hypothesized that increased intestinal permeability and barrier breakdown after burns is a TLR-4 dependent process hence, knocking down the TLR-4 gene would have a protective effect on burn-induced intestinal dysfunction. Male C57BL/6J (TLR-4 wild type [WT]) and C57BL/10ScN (TLR-4 knockout [KO]) mice were assigned randomly to either 30% total body surface area steam burn or sham injury. At 4 h, permeability to intraluminally administered fluorescein isothiocyanate (FITC)-dextran was assessed by measuring the fluorescence of the serum. Intestinal s les were analyzed for the presence of the tight junction protein occludin by immunoblotting and immunohistochemistry. Tumor necrosis factor (TNF)-alpha concentrations in the serum and intestines were measured by enzyme-linked immunosorbent assay at 2 h post-burn. Serum concentrations of FITC-dextran were decreased in TLR-4 KO mice compared with TLR-4 WT mice after burn injury (92.0 micrograms/mL and 264.5 micrograms/mL, respectively p < 0.05). After injury, no difference in intestinal permeability was observed between the TLR-4 KO mice and the TLR-4 WT sham-treated mice. The TLR-4 KO mice had preservation of occludin concentrations after thermal injury in both immunoblot and immunohistochemistry assays, but concentrations were decreased in TLR-4 WT animals. The serum concentrations of TNF-alpha serum were higher in TLR-4 WT burned animals than in the sham-treated mice. The TLR-4 KO animals had unmeasurable concentrations of TNF-alpha. No differences in TNF-alpha were observed in the intestinal tissue at 2 h. Mice with TLR-4 KO have less intestinal permeability to FITC-dextran than do TLR-4 WT mice after burn injury as a result of alterations in the tight junction protein occludin. These findings suggest that the greater intestinal permeability and barrier breakdown after burn injury is a TLR-4-dependent process. Toll-like receptor 4 may provide a useful target for the prevention and treatment of systemic inflammatory response syndrome and multisystem organ failure after injury.
Publisher: Elsevier BV
Date: 12-2005
DOI: 10.1111/J.1538-7836.2005.01621.X
Abstract: The incidence of postsurgical venous thromboembolism is thought to be low in Asian ethnic populations. We studied the incidence of deep-vein thrombosis (DVT) in Asian patients undergoing major orthopedic surgery of the lower limbs. We performed a prospective epidemiological study in 19 centers across Asia (China, Indonesia, South Korea, Malaysia, Philippines, Taiwan, and Thailand) in patients undergoing elective total hip replacement (THR), total knee replacement (TKR) or hip fracture surgery (HFS) without pharmacological thromboprophylaxis. The primary endpoint was the rate of DVT of the lower limbs documented objectively with bilateral ascending venography performed 6-10 days after surgery using a standardized technique and evaluated by a central adjudication committee unaware of local interpretation. Overall, of 837 Asian patients screened for this survey, 407 (48.6%, aged 20-99 years) undergoing THR (n = 175), TKR (n = 136) or HFS (n = 96) were recruited in 19 centers. DVT was diagnosed in 121 of 295 evaluable patients [41.0%, (95% confidence interval (CI): 35.4-46.7)]. Proximal DVT was found in 30 patients [10.2% (7.0-14.2)]. Total DVT and proximal DVT rates were highest in TKR patients (58.1% and 17.1%, respectively), followed by HFS patients (42.0% and 7.2%, respectively), then THR patients (25.6% and 5.8%, respectively). DVT was more frequent in female patients aged at least 65 years. Pulmonary embolism was clinically suspected in 10 of 407 patients (2.5%) and objectively confirmed in two (0.5%). The rate of venographic thrombosis in the absence of thromboprophylaxis after major joint surgery in Asian patients is similar to that previously reported in patients in Western countries.
Publisher: Wiley
Date: 03-1999
DOI: 10.1046/J.1440-1762.1999.00295.X
Abstract: There has been an exponential increase of warfarin usage in the community since several large and well-designed clinical trials have consistently found that warfarin can safely prevent embolic stroke in people with atrial fibrillation. Safe and effective warfarin treatment requires a case-by-case evaluation of each patient's clinical condition and risk factors for bleeding. It also demands a therapeutic partnership where patients can accept an educated responsibility for managing their own condition. This requires mutually understood plans for ongoing management, including dose adjustment and responses to under- or overdose and to bleeding complications.
Publisher: Elsevier BV
Date: 06-1988
DOI: 10.1016/0268-960X(88)90030-6
Abstract: The long-term use of oral anticoagulants like warfarin in artery disease has long been controversial. Possible aims of treatment include the primary or secondary prevention of systemic embolism, preventing recurrence after myocardial infarction or the progression of transient cerebral ischemia to a complete stroke, and the prevention of artery graft occlusion. The value of long-term anticoagulation is generally accepted in the few situations where, as in patients with mechanical heart valve prostheses, mitral valve disease and atrial fibrillation, or idiopathic dilated cardiomyopathy, the risk of arterial thromboembolism without anticoagulation is known to be high and there is good evidence that anticoagulants are effective, so the benefit:risk balance strongly favours their use. In many settings, however, it is hard to justify long-term warfarin treatment as the benefit:risk balance remains unknown either because the risk of thromboembolism without anticoagulation remains to be clearly defined (as in the case of patients with 'lone' atrial fibrillation), or because possible benefits have not been well documented (as after transient cerebral ischemia or peripheral vascular surgery). Finally, there is the difficult problem of estimating the benefit from long-term anticoagulation after myocardial infarction. It seems that warfarin can reduce the likelihood of non-fatal reinfarction with relative safety in highly selected patients, but whether it reduces mortality, and how its effect compares with that of other, more recent, therapies aimed at preventing reinfarction, remains unknown.
Publisher: Therapeutic Guidelines Limited
Date: 04-1998
Publisher: Elsevier BV
Date: 03-1989
DOI: 10.1016/0049-3848(89)90204-1
Abstract: The influence of an acute phase reaction on the size, weight, and fibrin content of experimental venous thrombi was examined in 10 pairs of rabbits. Jugular vein thrombosis was provoked by venous stasis plus mechanical injury 36 hours after one member of each pair received 0.5 ml/kg sterile turpentine in olive oil by subcutaneous injection. Fibrinogen level, factor VIII activity, and antithrombin III activity were significantly higher at the time of thrombus formation in turpentine treated rabbits, as were thrombus size (assessed by visual scoring), dry weight of thrombi, and their fibrin content (derived by measuring 125I-fibrinogen incorporation). In addition, the fibrinogen concentration correlated significantly with size, weight, and fibrin content of thrombi when results from turpentine treated and control animals were pooled, suggesting that plasma fibrinogen concentration at the time of thrombus formation may strongly influence the extent of thrombosis. This effect could help explain observations of a "hypercoagulable state" after injury.
Publisher: Wiley
Date: 12-1993
Publisher: Springer Science and Business Media LLC
Date: 12-1983
DOI: 10.2165/00003495-198326060-00006
Abstract: Thrombotic, rather than hemorrhagic, events represent a major complication of hypertension. This study aims to explore the mechanism of the hypercoagulative state in hypertension and to assess its clinical significance. The hypercoagulative state and even the prothrombotic state exists in patients with hypertension. This may be attributed to an impairment of the endothelium. A total of 81 patients suffering from essential hypertension were classified into 3 groups (grade 1: n = 27 grade 2: n = 36 grade 3: n = 18) and an additional 28 nonhypertensive patients were used as the control group. This study determined the changes of platelet activation marker P-selectin (CD62P), plasma fibrinogen, plasminogen activitor inhibitor-1 (PAI-1), and endothelium function. The percentage of CD62P+ platelets and the concentration of plasma fibrinogen and PAI-1 in the hypertension group was significantly higher than those in the control group. These increments coincided with the elevation of blood pressure. A significant difference was found between any of the 2 hypertension subgroups in the percentages of CD62P+ platelets (P < 0.001) and the concentration of PAI-I (P < 0.05). No difference was noted between the hypertension grade 1 and 2 groups in the concentration of plasma fibrinogen (P = 0.079) however, a significant difference was found between any of the other 2 subgroups (P < 0.001). Flow-mediated dilation (FMD) in the hypertension group was significantly lower than that in the control group. The hypercoagulative state exists in patients with hypertension and this state was more obvious with the elevation of blood pressure and coincided with an impairment in the degree of endothelium-dependent vasodilation.
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1111/JTH.12698
Abstract: Thrombosis is a common pathology underlying ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2010 documented that ischemic heart disease and stroke collectively caused one in four deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability. We performed a systematic review of the literature on the global disease burden caused by VTE in low-income, middle-income and high-income countries. Studies from western Europe, North America, Australia and southern Latin America (Argentina) yielded consistent results, with annual incidence rates ranging from 0.75 to 2.69 per 1000 in iduals in the population. The incidence increased to between 2 and 7 per 1000 among those aged ≥ 70 years. Although the incidence is lower in in iduals of Chinese and Korean ethnicity, their disease burden is not low, because of population aging. VTE associated with hospitalization was the leading cause of disability-adjusted life-years (DALYs) lost in low-income and middle-income countries, and the second most common cause in high-income countries, being responsible for more DALYs lost than nosocomial pneumonia, catheter-related bloodstream infections, and adverse drug events. VTE causes a major burden of disease across low-income, middle-income and high-income countries. More detailed data on the global burden of VTE should be obtained to inform policy and resource allocation in health systems, and to evaluate whether improved utilization of preventive measures will reduce the burden.
Publisher: Massachusetts Medical Society
Date: 13-09-2007
DOI: 10.1056/NEJMOA067703
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-1970
Publisher: AMPCo
Date: 06-2000
Publisher: Wiley
Date: 07-1981
DOI: 10.1111/J.1440-1673.1981.TB02242.X
Abstract: Epidemiologic methods have advanced tremendously in the last several decades. As important as they are, even the most sophisticated approaches are unable to provide meaningful answers when the user lacks a clear study question. Yet, instructors have more and more resources on how to conduct studies and analyze data but few resources on how to ask clearly defined study questions that will guide those methods. Training programs have limited time for coursework, and if novel statistical estimation methods become the focus of instruction, programs that go this route may end up underemphasizing the process of asking good study questions, designing robust studies, considering potential biases in the collected data, and appropriately interpreting the results of the analysis. Given the demands for space in curricula, now is an appropriate time to reevaluate what we teach epidemiology doctoral students. We advocate that programs place a renewed focus on asking good study questions and following a comprehensive approach to study design and data analysis in which questions guide the choice of appropriate methods, helping us avoid methods for methods' sake and highlighting when application of a new method can provide the opportunity to answer questions that were intractable with traditional approaches.
Publisher: AMPCo
Date: 1985
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1111/JTH.13153
Abstract: The AMPLIFY trial compared apixaban with enoxaparin followed by warfarin for the treatment of acute venous thromboembolism (VTE). To perform a subgroup analysis to compare the efficacy and safety of apixaban and enoxaparin followed by warfarin for the treatment of VTE in patients with cancer enrolled in AMPLIFY. Patients with symptomatic VTE were randomized to a 6-month course of apixaban or enoxaparin followed by warfarin. The primary efficacy outcome and principal safety outcome were recurrent VTE or VTE-related death and major bleeding, respectively. Of the 5395 patients randomized, 169 (3.1%) had active cancer at baseline, and 365 (6.8%) had a history of cancer without active cancer at baseline. Among patients with active cancer, recurrent VTE occurred in 3.7% and 6.4% of evaluable patients in the apixaban and enoxaparin/warfarin groups, respectively (relative risk [RR] 0.56, 95% confidence interval [CI] 0.13-2.37) major bleeding occurred in 2.3% and 5.0% of evaluable patients, respectively (RR 0.45, 95% CI 0.08-2.46). Among patients with a history of cancer, recurrent VTE occurred in 1.1% and 6.3% of evaluable patients in the apixaban and enoxaparin/warfarin groups, respectively (RR 0.17, 95% CI 0.04-0.78) major bleeding occurred in 0.5% and 2.8% of treated patients, respectively (RR 0.20, 95% CI 0.02-1.65). The results of this subgroup analysis suggest that apixaban is a convenient option for cancer patients with VTE. However, additional studies are needed to confirm this concept and to compare apixaban with low molecular weight heparin in these patients.
Publisher: BMJ
Date: 06-1989
DOI: 10.1136/ADC.64.6.855
Abstract: A boy with focal glomerulosclerosis as a result of nephrotic syndrome became unresponsive to corticosteroids and cyclophosphamide. He was given prolonged subcutaneous heparin with reduction in proteinuria, return of corticosteroid sensitivity, and no further deterioration (possibly improvement) in histological appearance. He remained completely well after five years.
Publisher: Georg Thieme Verlag KG
Date: 1974
Publisher: Elsevier BV
Date: 2003
DOI: 10.1046/J.1538-7836.2003.00006.X
Abstract: When a bleeding complication occurs during therapy with heparin or vitamin K antagonists, there is an option to give a specific antidote. Several new anticoagulants have been developed that are likely to have some risk of bleeding complications, for which no specific antidotes are available. Interestingly, it is unknown how often the use of an antidote is necessary in clinical practice. We investigated 1877 patients treated for venous thromboembolism included in three large clinical trials, of which 181 (9.6%) had a total of 225 adjudicated bleeding episodes 46 hemorrhages being designated as major. Some form of antidote was given to 26 (14.4%) patients with a hemorrhage. Of the patients with at least one major hemorrhage, 19 (41.3%) received an antidote. Vitamin K was given to 23 (1.2%) patients, one (0.05%) patient received protamin sulfate and seven (0.4%) patients received fresh frozen plasma. The use of antidotes was comparable for initial and long-term treatment. Antidotes were statistically significantly more frequently given in Canada as compared to other participating countries. Vitamin K was more frequently given in case of a higher international normalized ratio value. Although antidotes against anticoagulant treatment are widely available, our analysis shows that in only a very small number of patients a direct, or slow-acting antidote to reverse the anticoagulant effect was used.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.THROMRES.2014.08.014
Abstract: Thrombosis is a common pathology underlying ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). The Global Burden of Disease Study 2010 (GBD 2010) documented that ischemic heart disease and stroke collectively caused one in four deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability. We performed a systematic review of the literature on the global disease burden due to VTE in low, middle and high income countries. Studies from Western Europe, North America, Australia, and Southern Latin America (Argentina) yielded consistent results with annual incidences ranging from 0.75 to 2.69 per 1,000 in iduals in the population. The incidence increased to between 2 and 7 per 1,000 among those 70 years of age or more. Although the incidence is lower in in iduals of Chinese and Korean ethnicity, their disease burden is not low because of population aging. VTE associated with hospitalization was the leading cause of disability-adjusted-life-years (DALYs) lost in low and middle income countries, and second in high income countries, responsible for more DALYs lost than nosocomial pneumonia, catheter-related blood stream infections, and adverse drug events. VTE causes a major burden of disease across low, middle, and high income countries. More detailed data on the global burden of VTE should be obtained to inform policy and resource allocation in health systems, and to evaluate if improved utilization of preventive measures will reduce the burden.
Publisher: Massachusetts Medical Society
Date: 04-09-1997
DOI: 10.1056/NEJM199709043371001
Abstract: Hypoxia is a major regulator of tumor aggressiveness and metastasis in cancer progression. Exosomes (exos) play an important role in the communication between lung cancer and hypoxic microenvironment. However, the underlying mechanisms are largely undefined. Exos were isolated from A549 cells under hypoxia conditions. Transmission electron microscopy and nanoparticle tracking analysis were carried out to characterize exos. CCK-8 assay, flow cytometry, Western blot, wound healing, and transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of A549 cells, respectively. The M2 polarization of macrophages was evaluated by RT-qPCR and Western blot analysis. In vivo nude mice model was established to determine the regulatory effect of hypoxia/exos on the progression of lung cancer. Hypoxic A549 cell-derived exos (hypoxia/exos) promoted the proliferation and migration, and inhibited the apoptosis in A549 cells. The expression of PKM2 was significantly upregulated in hypoxia/exos. Hypoxic exosomal PKM2 induced M2 polarization of macrophages by activating AMPK pathway. Co-culture with hypoxia/exos-treated macrophages enhanced the migration, invasion, and epithelial-mesenchymal transition (EMT) in A549 cells. Moreover, treatment with hypoxia/exos facilitated the tumor growth and lung metastasis of A549 cells. Our findings reveal that hypoxic exosomal PKM2 induces M2 macrophage polarization via AMPK pathway, and thus exerts a simulative effect on the growth and metastasis of lung carcinoma.
Publisher: Georg Thieme Verlag KG
Date: 11-2016
DOI: 10.1160/TH16-02-0137
Abstract: Apixaban, a direct acting oral anticoagulant (DOAC), was found to be non-inferior to and safer as enoxaparin followed by warfarin for treatment of venous thromboembolism (VTE) in the AMPLIFY trial. Information is needed on how bleeding events with DOACs present and develop. In this post-hoc analysis, the clinical presentation and course of all major and clinically relevant non major (CRNM) bleeding events in the AMPLIFY trial were blindly classified by three investigators, using predesigned classification schemes containing four categories. Odds ratios (OR) for classifying as category three or four (representing a more severe clinical presentation and course) were calculated between apixaban and enoxaparin/warfarin. In total, 63 major and 311 CRNM bleeding events were classified. Of the major bleeds, a more severe clinical presentation occurred in 28.5% of apixaban versus 44.9% of enoxaparin/warfarin related recipients (OR 0.49, 95% confidence interval [CI] 0.14–1.78). A severe clinical course was observed in 14.3% and in 12.2%, respectively (OR 1.19, 95%CI 0.21–6.69). Of the CRNM bleeding events, a more severe clinical presentation and extent of clinical care was found in 25% of apixaban recipients compared to 22.7% in the enoxaparin/warfarin group (OR 1.13, 95%CI 0.65–1.97). The clinical presentation and course of major and CRNM bleeds were similar in apixaban and enoxaparin/warfarin treated patients. This finding should reassure physicians and patients that even in the absence of a specific reversal agent, apixaban is a convenient and safe choice for VTE.
Publisher: S. Karger AG
Date: 1998
DOI: 10.1159/000022408
Abstract: Because of the serious lack of useable, relevant information, most recommendations for prevention of thrombosis in non-surgical patients are extrapolations from much larger clinical trials experienced in surgery. Directly relevant evidence comes predominantly from very small randomized trials, many of them open label and carried out more than 20 years before the introduction of more recent and important changes in clinical care that may have substantially reduced the baseline thrombosis risk. In these early studies, low-dose heparin and low-molecular-weight heparins prevented subclinical deep vein thrombosis in ischaemic stroke, myocardial infarction and among elderly medical inpatients. Although it is likely that these drugs also prevent subclinical deep vein thrombosis after spinal cord injury or other major trauma, and when patients require intensive medical care, the supporting evidence in these circumstances comes mainly from cohort studies and poorly controlled comparisons. In contrast, the heparins have not reduced mortality or demonstrably prevented pulmonary embolism after ischaemic stroke or among elderly medical inpatients in large and well-conducted clinical endpoint trials, from which no clinically important benefit could be demonstrated. From analyses it is suggested that such benefit is probably more difficult to demonstrate for medical than for surgical patients. In the absence of sufficient information that is specific to medical patients, various forms of prophylaxis known to be effective in surgery will continue to be applied in high-risk in iduals. After venous thromboembolism, it now appears that the best duration of oral anticoagulant therapy to prevent a recurrence is determined to a greater extent by whether the thrombotic episode was idiopathic or triggered by a clinically recognizable cause, whether it was transient or continuing, and whether the deep vein thrombosis was extensive, limited to the calf veins or was a first or recurrent event.
Publisher: Wiley
Date: 05-2014
DOI: 10.1111/IMJ.12417
Abstract: A working group of clinicians and scientists was formed to review the clinical considerations for use of low-molecular-weight heparin (LMWH) biosimilars. LMWH are biological molecules of significant complexity the full complexity of chemical structure is still to be elucidated. LMWH biosimilars are products that are biologically similar to their reference product and rely on clinical data from a reference product to establish safety and efficacy. The complex nature of LMWH molecules means that it is uncertain whether a LMWH biosimilar is chemically identical to its reference product this introduces the possibility of differences in activity and immunogenicity. The challenge for regulators and clinicians is to evaluate the level of evidence required to demonstrate that a LMWH is sufficiently similar to the reference product. The consensus opinion of the working group is that prior to clinical use a LMWH biosimilar should have proven efficacy and safety, similar to the reference product with prospective studies, which should be confirmed with a proactive post-marketing pharmacovigilance programme.
Publisher: American Society of Hematology
Date: 15-09-2008
DOI: 10.1182/BLOOD-2008-05-160143
Abstract: We performed a randomized dose-ranging study, double-blind for rivaroxaban doses and open-label for the comparator (low-molecular-weight heparin followed by vitamin K antagonists) to assess the optimal dose of rivaroxaban for the treatment of deep vein thrombosis. A total of 543 patients with acute deep-venous thrombosis received rivaroxaban 20, 30, or 40 mg once daily or comparator. Treatment lasted for 84 days. The primary efficacy outcome was the 3-month incidence of the composite of symptomatic venous thromboembolic complications and asymptomatic deterioration in thrombotic burden as assessed by comparison of ultrasound and perfusion lung scanning at day 84 with baseline. The main safety outcome was the composite of major bleeding and clinically relevant nonmajor bleeding. A total of 449 (83%) of the 543 patients could be included in the per-protocol population. The primary efficacy outcome occurred in 6.1%, 5.4%, and 6.6% of the rivaroxaban 20-, 30-, and 40-mg treatment groups, respectively, and in 9.9% of those receiving standard therapy. The main safety outcome occurred in 5.9%, 6.0%, and 2.2% of the rivaroxaban 20-, 30-, and 40-mg treatment groups, respectively, and in 8.8% of those receiving standard therapy. These results with simple fixed-dose oral regimens justify phase 3 evaluations (www.ClinicalTrials.gov no.NCT00395772).
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: AMPCo
Date: 07-1969
Publisher: Massachusetts Medical Society
Date: 24-03-2011
DOI: 10.1056/NEJMC1100733
Publisher: American Society of Hematology
Date: 05-1989
DOI: 10.1182/BLOOD.V73.6.1592.1592
Abstract: Studies were performed to determine the cross-reaction rate of the heparin-dependent antibody with Org 10172, a new low molecular weight heparinoid, and to investigate the effect of Org 10172 on platelet activation induced by the antibody. The plasmas of 17 patients with thrombocytopenia induced by standard heparin were shown, by platelet aggregation studies, to contain the heparin-dependent antibody. Of these 17 patient plasmas, only three cross-reacted with the heparinoid, producing a cross-reaction rate of 18%. When Org 10172 was added to a reaction mixture containing normal platelet-rich plasma, patient plasma, and standard heparin with non-cross-reacting plasmas, it inhibited platelet aggregation and thromboxane B2 production induced by the antibody, provided that the ratio of Org 10172 concentration (anti- Xa U/mL) to standard heparin concentration (IU/mL) exceeded 2.5 to 5.0. This inhibitory effect was observed only with platelet activation mediated by the antibody, but not by collagen (2 micrograms/mL) or ADP (5.0 mumol/L). Additionally, three of 17 patients with serious thrombosis, whose plasma showed no cross-reaction with the heparinoid, received Org 10172 treatment with a good response in each case. These findings suggest that Org 10172 may be a useful drug for the treatment of heparin-induced thrombocytopenia.
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1111/JTH.12109
Abstract: New oral anticoagulants for thromboprophylaxis after hip or knee arthroplasty have been given as fixed-dose regimens. To evaluate the consistency of the antithrombotic efficacy and bleeding risk of apixaban 2.5 mg twice daily compared with enoxaparin 40 mg once daily after knee or hip arthroplasty across the clinical characteristics of age, gender, body weight, body mass index (BMI) and creatinine clearance. The pooled results of the ADVANCE-2 (knee arthroplasty) and -3 (hip arthroplasty) randomized trials were used to evaluate if treatment had a statistically significantly different effect (P < 0.10) on major venous thromboembolism (VTE) and bleeding for the characteristics of age, gender, body weight, BMI and creatinine clearance. Both univariate analysis and multivariate logistic regression were used. Univariate analyses identified statistically significant interactions for age and major VTE (P = 0.09) for both age (P = 0.07) and body weight (P = 0.07) and the outcome of major bleeding and for creatinine clearance (P = 0.03) and the composite outcome of major and clinically relevant non-major bleeding. Estimates of these possible differences were not precise, with wide 95% confidence intervals (CIs) that included a zero difference for several subgroups. Multivariate logistic regression analysis did not detect a statistically significant interaction for any outcomes. This analysis found no convincing evidence that age, weight, gender, BMI or creatinine clearance influenced the balance of benefit to risk for apixaban compared with enoxaparin. Because only 5% of patients had a creatinine clearance between 30 and 50 mL min(-1), further data are needed in such patients.
Publisher: Georg Thieme Verlag KG
Date: 1992
Abstract: We report the results of a double-blind, randomised trial of venous thrombosis (VT) prevention in 117 patients having elective hip replacement where low dose heparin alone (5,000 IU sodium heparin given subcutaneously [sc] 8 hourly until the seventh postoperative day) was compared with low dose heparin plus dihydroergotamine (DHE 0.5 mg, given 8 hourly by sc injection). The trial end point consisted of VT discovered through bilateral ascending venography done routinely on the seventh postoperative day. VT developed in 34% of patients given heparin/DHE (95% confidence interval = 22% – 47%) compared with 24% in those given low dose heparin alone (95% confidence interval = 14% – 37% p = 0.34), difference = 10% (95% confidence interval = –7% to +26%). Corresponding figures for the incidence of proximal (above-knee) thrombosis were 17% and 14% (95% confidence intervals = 8% – 29% and 6% – 25% respectively). These results are discussed in the context of a detailed overview of published evidence concerning VT prevention with heparin/DHE after hip replacement and we conclude it is unlikely that heparin/DHE is markedly superior to low dose heparin alone in this clinical setting.
Publisher: Georg Thieme Verlag KG
Date: 16-01-2019
Abstract: The double-blind, randomized, AMPLIFY trial compared 6 months' treatment with apixaban (10 mg twice daily for 7 days and 5 mg twice daily thereafter) versus conventional treatment (subcutaneous enoxaparin [1 mg/kg twice daily for ≥ 5 days] overlapped and followed by warfarin [international normalized ratio = 2.0–3.0]) in patients with acute venous thromboembolism (VTE). This post hoc analysis of AMPLIFY compared outcomes among those taking or not taking concomitant anti-platelet therapy. The primary efficacy outcome was recurrent VTE or VTE-related death the principal safety outcome was major bleeding. Of 5,365 (apixaban, n = 2,676 enoxaparin/warfarin, n = 2,689) randomized patients, 813 (apixaban, n = 402 [15%] enoxaparin/warfarin, n = 411 [15%]) took concomitant anti-platelet therapy, of which 92% consisted of low-dose aspirin. Rates of VTE or VTE-related death were similar whether or not anti-platelet agents were taken (apixaban: 3.6 and 2.0% enoxaparin/warfarin: 3.0 and 2.6% anti-platelet use: relative risk [RR], 1.23 95% confidence interval [CI], 0.58–2.62 no anti-platelet use: RR, 0.77 95% CI, 0.52–1.13) interaction p-value = 0.299. Major bleeding rates were threefold higher in those taking versus those not taking anti-platelet agents (apixaban: 1.2 and 0.4% enoxaparin/warfarin: 4.1 and 1.4% anti-platelet use: RR, 0.30 95% CI, 0.11–0.81 no anti-platelet use: RR, 0.31 95% CI, 0.15–0.63) interaction p-value = 0.924. Concomitant anti-platelet therapy produced a proportionally similar increase in major bleeding in patients randomized to apixaban or conventional therapy, but there were fewer major bleeds with apixaban. Therefore, the overall safety of apixaban over conventional therapy was maintained in patients receiving anti-platelet therapy. Clinicaltrials.gov: NCT00643201.
Publisher: AMPCo
Date: 1994
Publisher: AMPCo
Date: 09-1994
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2014
DOI: 10.1161/ATVBAHA.114.304488
Abstract: Thrombosis is the common pathology underlying ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). The Global Burden of Disease Study 2010 (GBD 2010) documented that ischemic heart disease and stroke collectively caused 1 in 4 deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability. To review the literature on the global burden of disease caused by VTE. We performed a systematic review of the literature on the global disease burden because of VTE in low-, middle-, and high-income countries. Studies from Western Europe, North America, Australia, and Southern Latin America (Argentina) yielded consistent results with annual incidences ranging from 0.75 to 2.69 per 1000 in iduals in the population. The incidence increased to between 2 and 7 per 1000 among those aged ≥70 years. Although the incidence is lower in in iduals of Chinese and Korean ethnicity, their disease burden is not low because of population aging. VTE associated with hospitalization was the leading cause of disability-adjusted life-years lost in low- and middle-income countries, and second in high-income countries, responsible for more disability-adjusted life-years lost than nosocomial pneumonia, catheter-related blood stream infections, and adverse drug events. VTE causes a major burden of disease across low-, middle-, and high-income countries. More detailed data on the global burden of VTE should be obtained to inform policy and resource allocation in health systems and to evaluate whether improved use of preventive measures will reduce the burden.
Publisher: Elsevier BV
Date: 03-2010
Publisher: American College of Physicians
Date: 19-11-2019
Publisher: Massachusetts Medical Society
Date: 19-11-2009
DOI: 10.1056/NEJMC091817
Publisher: Informa UK Limited
Date: 1974
DOI: 10.1080/00325481.1974.11713670
Abstract: Saussurea lappa has been reported to possess anti-atopic properties. In this study, we have confirmed the S. lappa's anti-atopic properties in Nc/Nga mice and investigated the candidate gene related with its properties using microarray. We determined the target gene using real time PCR in in vitro experiment. S. lappa showed the significant reduction in atopic dermatitis (AD) score and immunoglobulin E compared with the AD induced Nc/Nga mice. In the results of microarray using back skin obtained from animals, we found that S. lappa's properties are closely associated with cytokine-cytokine receptor interaction and the JAK-STAT signaling pathway. Consistent with the microarray data, real-time RT-PCR confirmed these modulation at the mRNA level in skin tissues from S. lappa-treated mice. Among these genes, PI3Kca and IL20Rβ were significantly downregulated by S. lappa treatment in Nc/Nga mouse model. In in vitro experiment using HaCaT cells, we found that the S. lappa components, including alantolactone, caryophyllene, costic acid, costunolide and dehydrocostus lactone significantly decreased the expression of PI3Kca but not IL20Rβ in vitro. Therefore, our study suggests that PI3Kca-related signaling is closely related with the protective effects of S. lappa against the development of atopic-dermatitis.
Publisher: Springer Science and Business Media LLC
Date: 2197
DOI: 10.2165/00003495-197612010-00002
Abstract: There are three categories of antithrombotic agents: drugs which prevent fibrin fromation (the anticoagulants and defibrinating enzymes), drugs which prevent platelet adhesion or aggregation (the antiplatelet drugs), and thrombolytic drugs which induce fibrin degradation. Clinical studies have now led to a better understanding of the relative value of these drugs in different thrombotic disorders. In addition, knowledge of the mechanism of action of some of these drugs has recently been much advanced. The anticoagulant drugs in clinical use are heparin and the oral anticoagulants. Heparin is a potent inhibitor of several steps on the intrinsic coagulation pathway through its effect on a plasma cofactor, antithrombin III. its action is immediate, but heparin must be given parenterally. Oral anticoagulants act more slowly, by reducing the hepatic synthesis of biologically active factors II, VII, IX and X, but can be given by mouth. Heparin is therefore most suitable for starting anticoagulant treatment, while oral anticoagulants are generally used for prolonged therapy. The value of the anticoagulants as antithrombotic agents has been best assessed by studying their effectiveness in preventing and treating venous thromboembolic disease. Oral anticoagulants have been repeatedly shown to prevent venous thrombosis and pulmonary embolism in patients at high risk of developing these complications. However, the increased risk of postoperative bleeding has prevented their widespread use for this purpose in surgical patients. Recently, the use of low doses of heparin, given subcutaneously before and after surgery, has been shown to markedly reduce the incidence of venous thrombosis and pulmonary embolism (including fatal pulmonary embolism) after major elective abdominal surgery, and to produce only a slight increase of postoperative bleeding. This represents a major advance in anticoagulant prophylaxis of venous thromboembolism insurgical patients. However, low dose heparin prophylasix is relatively ineffective in patients having hip surgery, and has not been evaluated in patients having other types of orthopaidic surgery. There is direct evidence that antocoagulant therapy prevents death and recurrent embolism in patients who have developed pulmonary embolism, and considerable indirect evidence that it prevents pulmonary embolism, and considerable indirect evidence that it prevents pulmonary embolism (and death from pulmonary embolism) in patients who have venous thrombosis. The incidence of further venous thromboembolism or bleeding during treatment appears to be minimised when heparin is given by continuous intravenous infusion in a dose sufficient to produce a moderate, but no excessive, prolongation of a heparin-sensitive, in vitro coagulation test. The tests most commonly used to monitor heparin therapy was based on either the whole blood clotting time or the activated partial thromboplastin time...
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.JCRC.2014.02.004
Abstract: Thrombocytopenia occurs in 20% to 45% of critically ill medical-surgical patients. The 4Ts heparin-induced thrombocytopenia (HIT) score (with 4 domains: Thrombocytopenia, Timing of thrombocytopenia, Thrombosis and oTher reason[s] for thrombocytopenia) might reliably identify patients at low risk for HIT. Interobserver agreement on 4Ts scoring is uncertain in this setting. To evaluate whether a published clinical prediction rule (the "4Ts score") reliably rules out HIT in "low-risk" intensive care unit (ICU) patients as assessed by research coordinators (who prospectively scored) and 2 adjudicators (who scored retrospectively) during an international heparin thromboprophylaxis trial (PROTECT, NCT00182143). Of 3746 medical-surgical ICU patients in PROTECT, 794 met the enrollment criteria for this HIT substudy. Enrollment was predicated on one of the following occurring in ICU: platelets less than 50×10(9)/L, platelets decreased to 50% of ICU admission value (if admission value<100×10(9)/L), any venous thrombosis, or if HIT was otherwise clinically suspected. Independently, 4Ts scores were completed in real time by research coordinators blinded to study drug and laboratory HIT results, and retrospectively by 2 adjudicators blinded to study drug, laboratory HIT results, and research coordinators' scores the adjudicators arrived at consensus in all cases. Of the 763 patients, 474 had a central or local laboratory HIT test performed and had 4Ts scoring by adjudicators 432 were scored by trained research coordinators. Heparin-induced thrombocytopenia was defined by a centrally performed positive serotonin release assay (SRA). Of the 474 patients with central adjudication, 407 (85.9%) had a 4Ts score of 3 or lower, conferring a low pretest probability (PTP) of HIT of these, 6 (1.5% [95% confidence interval, 0.7%-3.2%) had a positive SRA. Fifty-nine (12.4%) had a moderate PTP (4Ts score of 4-5) of these, 4 (6.8%) had a positive SRA. Eight patients had a high PTP (4Ts score of ≥6) of these, 1 (12.5%) had a positive SRA. Raw agreement between research coordinators and central adjudication on each domain of the 4Ts score and low, intermediate, and high PTP was good. However, chance-corrected agreement was variable between adjudicators (weighted κ values of 0.31-0.93) and between the adjudicator consensus and research coordinators (weighted κ values of 0.13 and 0.78). Post hoc review of the 6 SRA-positive cases with an adjudicated low PTP demonstrated that their scores would have been increased if the adjudicators had had additional information on heparin exposure prior to ICU admission. In general, the fourth domain of 4Ts (oTher causes of thrombocytopenia) generated the most disagreement. Real-time 4Ts scoring by research coordinators at the time of testing for HIT was not consistent with 4Ts scores obtained by central adjudicators. The results of this comprehensive HIT testing highlight the need for further research to improve the assessment of PTP scoring of HIT for critically ill patients.
Publisher: Elsevier BV
Date: 08-2011
Abstract: Some patients with acute VTE who may previously have been exposed to heparin products have unrecognized antibodies implicated in heparin-induced thrombocytopenia (HIT). Antibody prevalence and patient consequences upon exposure to heparin, low-molecular-weight heparin, and fondaparinux are uncertain. In this secondary analysis, we tested patients in the Matisse VTE studies at study entry for heparin-dependent antibodies and further tested patients with enzyme-linked immunosorbent assay (ELISA)-positive results for platelet-activating antibodies. We compared the risk of HIT (> 50% fall in platelet count, heparin-dependent antibodies, no contradicting features) between patients treated with heparin (either unfractionated or low molecular weight [enoxaparin]) vs those who received fondaparinux. Comparison groups for thrombocytopenia occurrence comprised patients with ELISA-positive, platelet-activating, antibody-positive results ELISA-positive, but platelet-activating antibody-negative results and randomly selected antibody-negative results. A total of 127 of 3,994 patients (3.2%) had ELISA-positive results at baseline, but only 14 (0.4% 95% CI, 0.2%-0.6%) had platelet-activating antibodies. Among these 14, four treated with unfractionated or low-molecular-weight heparin developed HIT compared with zero of 10 fondaparinux-treated patients (OR, 95 95% CI, 8-1,123 P < .001). This frequency (four of four, 100%) significantly differed from that of both heparin-treated patients whose results were ELISA positive but platelet-activating antibody negative and from heparin-treated antibody-negative control subjects (zero of 15 and zero of 27, respectively P < .001 for both). Of patients with VTE, 0.4% had pathologic platelet-activating heparin-dependent antibodies rather than the 3.2% detected by the recommended cutoff of the commercial ELISA. Among study patients with acute VTE who had platelet-activating antibodies, treatment with fondaparinux reduced the risk of precipitating rapid-onset HIT.
Publisher: Wiley
Date: 24-06-2015
DOI: 10.1111/BJH.13538
Publisher: Springer Science and Business Media LLC
Date: 05-08-2008
Abstract: In a registry of 15,520 patients treated for symptomatic deep vein thrombosis or pulmonary embolism (PE), the 90-day mortality was 8.65% and death was attributed to PE in 1.68% of patients (19.4% of all deaths). Multivariate analysis defined five simple predictors of death from PE during the first 3 months after presentation. The odds ratio for fatal PE was raised to 5.4 by initially nonmassive symptomatic PE (compared with deep vein thrombosis and no symptoms of PE), to 17.5 by initially massive PE (systolic blood pressure below 90 mmHg), 4.9 by immobility as a result of neurological disease, 2.5 by age over 75 years, and 2.0 by the presence of cancer. Of all the deaths from PE, 75% occurred within 12 days of presentation and 50% occurred within 5 days. These results reinforce previous observations that also linked symptomatic PE, massive PE, old age, and cancer to a raised likelihood of death from PE despite appropriate therapy.
Publisher: Wiley
Date: 02-1980
DOI: 10.1111/J.1445-5994.1980.TB03414.X
Abstract: After observing a patient with heparin-induced thrombocytopenia we prospectively recorded the incidence of thrombocytopenia associated with heparin treatment by measuring the platelet count every second day in 166 patients given therapeutic heparin for various thromboembolic disorders, and 51 patients given low-dose heparin prophylaxis. A platelet count below 100 x 10(9)/litre developed in nine patients (5.4%) during or soon after full-dose heparin therapy, and in one patient given low-dose heparin. Careful clinical review suggested that heparin was either the most likely cause of a contributing cause of thrombocytopenia in 5/166 patients (3.0%) receiving therapeutic heparin and none of the patients who received prophylactic heparin. Associated laboratory studies suggest that heparin-initiated platelet aggregation in vivo is a useful marker for heparin-induced thrombocytopenia.
Publisher: Schattauer GmbH
Date: 1975
Abstract: Reduced platelet survival has been found in patients who have reccurrent VTE despite anticoagulant treatment, impaired fibrinolytic activity has been found in patients with recurrent VTE, and a reduced AT III level occurs in some families with VTE. This has led to the use of drugs which correct these abnormalities in patients with VTE. However, the incidence of these, and other, abnormalities of hemostasis in unselected patients with VTE is not known. We have measured 51 Cr-platelet survival, euglobulin lysis time (ELT) before and after venous tourniquet occlusion, antiplasmin activity, AT III level, and 125 I-fibrinogen survival in 57 patients documented by venography (49 patients) or lung scan (8 patients). All studies were done off treatment and at least 3 months after the most recent episode of VTE. The mean platelet half-time in patients was similar to the in 42 controls, but 7 patients with VTE (12%) had a reduced platelet half-time. The ELT was significantly longer (p 0.005), before and after tourniquet occlusion, than in 89 controls. Thus, 40% of patients and only 10% of controls had a ELT longer than 240 minutes after tourniquet occlusion. AT III levels were normal, as was fibrinogen survival. An elevated antiplasmin level was found in one patient in this study and in two others studied while still under treatment with anticoagulants-all 3 had thromboembolic pulmonary hypertension. Abnormalities occurred with equal frequency in patients with idiopathic or secondary, and single episodes or recurrent VTE. These findings suggest that impaired fibrinolytic activity occurrs frequently in VTE, but that reduced platelet survival is uncommon. High antiplasmin levels may predispose to thromboembolic pulmonary hypertension.
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1111/J.1538-7836.2007.02565.X
Abstract: Selecting initial anticoagulant dose by patient weight for acute pulmonary embolism and deep vein thrombosis has clinical credibility however, uncertainty remains regarding how to dose obese patients with newer anticoagulants because outcome data are sparse. To use the Matisse trials' comparison of sc fondaparinux once daily with control heparin therapies (intravenous unfractionated heparin for pulmonary embolism, sc enoxaparin 1 mg/kg b.i.d. for deep vein thrombosis) for initial treatment in order to compare primary outcomes (venous thromboembolism recurrence and major bleeding) in obese patients. Primary outcomes were compared in subsets composed of patients weighing 100 kg and with body mass index (BMI) or = 30 kg/m(2). Medians and ranges for weight and BMI were compared for patients suffering either recurrence or major bleeding. Twenty-two thousand and one patients received fondaparinux and 2217 received enoxaparin or unfractionated heparin. Four hundred and ninety-six patients (11%) weighed > 100 kg and 1216 (28%) had a BMI > or = 30. Treatment groups had similar characteristics. The upper limit in subject weight for recurrence was 166 kg (BMI 58), and for major bleeding 120 kg (BMI 39). The incidences of recurrence and major bleeding were similar for each patient subset of weight and BMI for both fondaparinux and heparin treatment groups. Among patients with a primary outcome, median weights and BMIs were also similar. The current recommended doses of fondaparinux and heparins for the treatment of venous thromboembolism appear to provide similar protection against recurrence and major bleeding to one another and to obese and non-obese patients.
Publisher: S. Karger AG
Date: 2000
DOI: 10.1159/000054166
Abstract: Clinical trials and meta-analyses have shown that low-molecular-weight heparin and unfractionated heparin are effective in preventing deep vein thrombosis (DVT) in acutely ill medical inpatients who are at risk as they are likely to be bedridden for 6 days or more. It is not known, however, if such prophylaxis can also reduce the likelihood of fatal pulmonary embolism or decrease all-causes mortality in this patient population. No recommendations can be made regarding thromboprophylaxis in those at a lower risk of venous thromboembolism or in short-stay inpatients, as these have not yet undergone clinical trial. Current evidence suggests that high doses of heparin should be avoided after an acute ischaemic stroke, as the results of recent large trials suggest any potential treatment benefit in preventing DVT is cancelled by the increased intracranial bleeding risk caused from the underlying disease.
Publisher: Massachusetts Medical Society
Date: 14-03-1996
Publisher: Springer Berlin Heidelberg
Date: 2011
Publisher: Wiley
Date: 10-1999
DOI: 10.1111/J.1445-5994.1999.TB01623.X
Abstract: A warfarin loading protocol adjusting doses for age was compared to both Fennerty's protocol (Fenn) and empirical dosing (Emp). Patients beginning warfarin were randomised to receive doses according to either the age adjusted (Age) protocol or Fenn. Data were retrospectively collected for patients who had begun warfarin in the previous six months to represent empirical dosing. The study was performed on inpatients being commenced on warfarin for the first time at two teaching hospitals. Endpoints were time to reach a stable, therapeutic International Normalised Ratio (INR) between 2-3, the number of patients experiencing an INR > or =4 in the first week and the number of patients who had a dose held in the first week. Thirty-five patients were assessed in the Age group, 28 in the Fenn group, and 123 patients for the Emp group. Patients using the Age protocol achieved a stable, therapeutic INR more rapidly than either the Fenn (p=0.003, log rank test) or Emp (p or =4 in the first week (p<0.05) as well as a lower proportion having doses held in the first week (p<0.01). There were no differences between Emp and Fenn for any of the endpoints. Adjustment of warfarin loading doses for age exhibits clear superiority over the use of Fenn or Emp. This becomes increasingly important as the average age of patients being warfarinised increases, with the recognition that atrial fibrillation requires anticoagulation. Fenn consistently overdosed elderly patients, especially those aged 80 years and older.
No related grants have been discovered for Alexander Gallus.