ORCID Profile
0000-0002-7743-4515
Current Organisation
Murdoch University
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1998
DOI: 10.1097/00001721-199801000-00005
Abstract: Light-to-moderate alcohol intake is associated with a reduced incidence of ischaemic cardiovascular events, whilst heavy alcohol intake can predispose in iduals to stroke. Alcohol-induced changes in coagulation and fibrinolysis may be relevant and are the subject of this controlled trial of varying alcohol intake in 55 predominantly beer-drinking men. Following 4 weeks stabilization maintaining usual drinking habits, participants were randomized to either continue usual alcohol intake or to restrict alcohol by changing to low alcohol beer for 4 weeks. In a final 4 week period, they crossed over to low or usual alcohol intake, respectively. Comparing combined low and usual alcohol periods, an increase in mean weekly alcohol intake from 92 to 410 ml (mean daily intake from 13 to 58 ml) was associated with a decrease in plasma fibrinogen (by 11%, P < 0.001) and platelet count (3%, P < 0.05), but increases in factor VII (7%, P = 0.001), tissue plasminogen activator (tPA 16%, P = 0.01) and plasminogen activator inhibitor-1 (PAI-1 21%, P < 0.001). The ratio, tPA/PAI-1, fell from 0.50 to 0.44 (P = 0.02) confirming the relatively greater increase in PAI-1 with alcohol consumption. Two lipid-associated natural anticoagulants, tissue factor pathway inhibitor and beta 2-glycoprotein-I, did not change. The substantial reduction in plasma fibrinogen with alcohol intake may well contribute to the apparent protection alcohol confers against ischaemic coronary and cerebral events. The increase in factor VII and relatively greater increase in PAI-1 than tPA with alcohol intake may attenuate this benefit and indeed may sufficiently predispose in iduals to thrombosis to contribute to the increased incidence of ischaemic stroke seen in heavier drinkers. The balance of anticoagulant and procoagulant and fibrinolytic effects in any in idual may vary depending on quantity and type of alcoholic beverage ingested, as well as on genetic and other variables, all of which merit further study.
Publisher: Elsevier BV
Date: 12-1995
Publisher: SAGE Publications
Date: 06-07-2012
Abstract: Antiphospholipid antibodies contribute to the development of thrombosis, although precise mechanisms remain to be elucidated. We determined the effects of affinity-purified anti-beta 2 -glycoprotein 1 (anti-β 2 GP1) and anti-prothrombin (anti-PT) antibodies on in vitro platelet aggregation. Adenosine diphosphate (ADP) and collagen-induced platelet aggregation were performed using platelet-rich plasma ([PRP] 250 × 10 9 /L). Antiphospholipid antibodies (1.25-10 μg/mL) were preincubated with PRP for 10 minutes at 37°C prior to the addition of agonist. Anti-β 2 GP1 antibodies significantly reduced platelet aggregation (percentage area under the curve %AUC) in a concentration-dependent manner using both 5 μmol/L ( P .001) and 2.5 μmol/L ( P = .038) ADP but did not significantly affect the rate of aggregation. Anti-PT antibodies significantly enhanced 5 µg/mL collagen-induced platelet aggregation (%AUC P = .034) but did not affect ADP-induced platelet aggregation. These results suggest (1) interactions and effects of antiphospholipid antibodies on platelets are agonist and concentration dependent and (2) anti-β 2 GP1 antibodies may inhibit dense granule release and/or inhibition of the arachidonic acid pathway.
Publisher: SAGE Publications
Date: 09-11-2017
Abstract: Anti-beta-2-glycoprotein 1 (anti-β 2 GP1) antibodies are associated with increased thrombotic risk in patients with autoimmune disease. There is conflicting evidence on the effects of anti-β 2 GP1 antibodies on platelets, with both enhanced and inhibited aggregation previously reported. However, previous studies did not include isotype antibodies to ensure the observed effects were due to anti-β 2 GP1 antibodies. The aims of this study were to (1) investigate the effects of anti-β 2 GP1 antibodies on collagen-induced platelet aggregation in parallel with negative control (buffer normal saline) and isotype control antibodies and (2) determine the lupus anticoagulant (LA) activity of anti-β 2 GP1 antibodies used. Three animal-derived anti-human-β 2 GP1 antibodies (1.25, 2.5, and 5 μg/mL) incubated with healthy platelet-rich plasma were activated by collagen (2.5 μg/mL). Each anti-β 2 GP1 antibody demonstrated the inhibition of aggregation compared to negative control, but not to isotype control. No anti-β 2 GP1 antibody demonstrated LA activity, suggesting they were probably nonpathological. This study highlights both negative and isotype control markers are important to validate the effects of anti-β 2 GP1 antibodies. Assays to measure anti-domain I-β 2 GP1 antibodies are recommended to be used in conjunction with functional measures to further investigate the effects of anti-β 2 GP1 antibodies.
Publisher: Springer Science and Business Media LLC
Date: 21-03-2012
DOI: 10.1038/EJCN.2012.28
Abstract: Hyperglycaemia is associated with increased platelet aggregation that increases the risk of thrombosis in people with type-2 diabetes and cardiovascular disease. Low glycemic index (GI) meals high in carbohydrate or moderately high in protein have been shown to acutely reduce postprandial excursions of plasma glucose and insulin compared with high carbohydrate high GI meals. However, it is not known whether these differences in glucose and insulin profile also impact on postprandial platelet aggregation. This study aimed to investigate the acute effects of three iso-energetic meals, on measures of postprandial platelet aggregation, in healthy in iduals. A randomised cross-over study compared the acute effects of a high GI high carbohydrate (HGI-HC), a low GI high carbohydrate (LGI-HC) and a low GI moderately high in protein and fat (LGI-MPF) meal on postprandial platelet aggregation, glucose, insulin and triglyceride concentrations. Comparisons were made at fasting, 60 and 120 min postprandially. A total of 32 volunteers (mean ± s.d. age 59.9 ± 11.7 years, BMI 27.1 ± 3.7 kg/m(2)) participated in the study. Results showed significant reductions in maximum platelet aggregation postprandially with nonsignificant differences (all P > 0.29) between the three meals. Glucose and insulin were significantly (both P 0.25) between the three test meals. In healthy in iduals platelet aggregation is reduced postprandially but this decrease is similar between meals of different GI that induce different glucose and insulin responses.
Publisher: Springer Science and Business Media LLC
Date: 04-09-2015
DOI: 10.1007/S00592-015-0802-4
Abstract: People with type 2 diabetes mellitus (T2DM) have abnormal peripheral and central haemodynamics at rest and during exercise, probably due to metabolic perturbations, but mechanisms are unknown. We used untargeted metabolomics to determine the relationships between metabolic perturbations and haemodynamics (peripheral and central) measured at rest and during exercise. Serum s les from 39 participants with T2DM (62 ± 9 years 46 % male) and 39 controls (52 ± 10 years 51 % male) were analysed by liquid chromatography-mass spectrometry, nuclear magnetic resonance spectroscopy and principal component analysis. Scores on principal components (PC) were used to assess relationships with haemodynamics including peripheral and central BP, central augmentation index (AIx) and central augmentation pressure (AP). Participants with T2DM had higher resting and exercise haemodynamics (peripheral and central BP, central AIx and central AP) compared to controls (p < 0.05). PC that comprised of a signature metabolic pattern of T2DM was independently associated with resting and exercise central AIx and central AP (p < 0.05). Serum metabolic profile was associated with central, but not peripheral, haemodynamics in T2DM participants, suggesting that metabolic irregularities may explain abnormal central haemodynamics in T2DM patients.
Publisher: Georg Thieme Verlag KG
Date: 04-2009
Abstract: Thrombosis is a major cause of morbidity and mortality in Western countries and is associated with a range of chronic diseases such as cardiovascular disease, renal disease, diabetes, and various autoimmune conditions. Improved health care and approaches to the treatment of disease are leading to aging populations that will probably result in an increase in the incidence of thrombosis and associated manifestations over the next few decades. Adopting a physically active lifestyle through regular exercise has been proposed to lower the risk of developing thrombosis. Indeed, it has been demonstrated that exercise is beneficial for health, although there is inconsistent data from studies investigating the effect of exercise on the risk of thrombosis, with reports of both increased and decreased risk across a variety of cohorts. Studies in this area are difficult to critique due to the variety of confounders such as age, body composition, fitness level, underlying disease and treatment, as well as exercise intensity, frequency, duration, and energy expenditure. In younger in iduals and those with chronic conditions such as cardiovascular and kidney disease, there is evidence that physical activity is beneficial for the lowering of thrombotic risk, whereas in older in iduals the risk is more likely to be unchanged or increased. This review will explore whether exercise is a "friend" or "foe" in lowering the risk of thrombosis. It will also discuss whether elite athletes have a lower risk of thrombosis and whether exercise may help to reduce thrombotic risk in in iduals with chronic disease.
Publisher: Wiley
Date: 04-05-2016
Abstract: Vanilloid-like agents, including capsaicin, N-arachidonoyl-dopamine and N-oleoyldopamine inhibit platelet aggregation, however little is known about the precise mechanism(s) of action. The authors have previously shown that blocking of the capsaicin receptor, transient receptor potential vanilloid-1 (TRPV1), does not interfere with capsaicin action during adenosine diphosphate (ADP)-induced aggregation. This research is extended to investigate the effect of these vanilloid-like-agents on platelet count, and to test whether the effect of these agents is mediated through TRPV1 and/or cannabinoid (CB1 and CB2) receptors in the presence of other agonists, including collagen and arachidonic acid. Incubation of platelets with each of the in idual vanilloids, or with receptor antagonists of TRPV1 (SB452533), CB1 (AM251) and CB2 (AM630), for up to 2 h did not significantly affect the platelet count. Similarly, the effect of in idual vanilloids on the inhibition of platelet aggregation was not significantly different in the presence of receptor agonists compared to control, irrespective of the agonist used, suggesting that the inhibitory effect of vanilloids on platelet aggregation is independent of TRPV1, CB1 and CB2 receptors. Further research on the antiplatelet activity of vanilloids should focus on mechanisms other than those associated with vanilloid receptors.
Publisher: SAGE Publications
Date: 19-06-2008
Abstract: The release of tissue factor pathway inhibitor (TFPI) from human umbilical vein endothelial cells (HUVECs) was investigated using heparin and phospholipase C. The experiment included incubating HUVECs with 0, 1, or 10 U/mL heparin diluted in Dulbecco Modified Eagle's Medium plus 5% fetal calf serum for 1 or 24 hours. A statistically significant increase in TFPI activity levels was seen at 1 hour, but not at 24 hours. A 20-fold increase in the release of TFPI after phospholipase C treatment of HUVECs was demonstrated, confirming that it is glycosylphosphatidylinositol-lipid (GPI) anchored. Sequential treatment of HUVECs with phospholipase C and heparin was performed, and a trend was observed where GPI-anchored TFPI levels were increased after 1 hour of pretreatment with heparin but were decreased after 24 hours. Serum is a requirement for the heparin-dependent release of TFPI from HUVECs. Heparin pretreatment of HUVECs may affect levels of GPI anchored TFPI in a time and dose-dependent manner.
Publisher: Georg Thieme Verlag KG
Date: 04-02-2021
DOI: 10.1055/A-1382-9983
Abstract: Background High estradiol (E2) levels are linked to an increased risk of venous thromboembolism however, the underlying molecular mechanism(s) remain poorly understood. We previously identified an E2-responsive microRNA (miR), miR-494–3p, that downregulates protein S expression, and posited additional coagulation factors, such as tissue factor, may be regulated in a similar manner via miRs. Objectives To evaluate the coagulation capacity of cohorts with high physiological E2, and to further characterize novel E2-responsive miR and miR regulation on tissue factor in E2-related hypercoagulability. Methods Ceveron Alpha thrombin generation assay (TGA) was used to assess plasma coagulation profile of three cohorts. The effect of physiological levels of E2, 10 nM, on miR expression in HuH-7 cells was compared using NanoString nCounter and validated with independent assays. The effect of tissue factor-interacting miR was confirmed by dual-luciferase reporter assays, immunoblotting, flow cytometry, biochemistry assays, and TGA. Results Plasma s les from pregnant women and women on the contraceptive pill were confirmed to be hypercoagulable (compared with sex-matched controls). At equivalent and high physiological levels of E2, miR-365a-3p displayed concordant E2 downregulation in two independent miR quantification platforms, and tissue factor protein was upregulated by E2 treatment. Direct interaction between miR-365a-3p and F3-3′UTR was confirmed and overexpression of miR-365a-3p led to a decrease of (1) tissue factor mRNA transcripts, (2) protein levels, (3) activity, and (4) tissue factor-initiated thrombin generation. Conclusion miR-365a-3p is a novel tissue factor regulator. High E2 concentrations induce a hypercoagulable state via a miR network specific for coagulation factors.
Publisher: Springer Science and Business Media LLC
Date: 25-12-2015
DOI: 10.1007/S00421-014-3087-3
Abstract: A hypertensive response to moderate intensity exercise (HRE) is associated with increased cardiovascular risk. The mechanisms of an HRE are unclear, although previous studies suggest this may be due to haemostatic and/or haemodynamic factors. We investigated the relationships between an HRE with haemostatic and hemodynamic indices. Sixty-four participants (57 ± 10 years, 71 % male) with indication for exercise stress testing underwent cardiovascular assessment at rest and during moderate intensity exercise, from which 20 participants developed an HRE (defined as moderate exercise systolic BP ≥ 170 mmHg/men and ≥ 160 mmHg/women). Rest, exercise and post-exercise blood s les were analysed for haemostatic markers, including von Willebrand factor (vWf), and haemodynamic measures of brachial and central blood pressure (BP), aortic stiffness and systemic vascular resistance index (SVRi). HRE participants had higher rest vWf compared with normotensive response to exercise (NRE) participants (1,927 mU/mL, 95 % CI 1,240-2,615, vs. 1,129 mU/mL, 95 % CI 871-1,386 p = 0.016). vWf levels significantly decreased from rest to post-exercise in HRE participants (p = 0.005), whereas vWf levels significantly increased from rest to exercise in NRE participants (p = 0.030). HRE participants also had increased triglycerides, rest BP, aortic stiffness and exercise SVRi (p < 0.05 for all). Rest vWf predicted exercise brachial systolic BP (β = 0.220, p = 0.043 adjusted R (2) = 0.451, p < 0.001) independent of age, sex, body mass index, triglycerides, rest brachial systolic BP and aortic stiffness. Increased rest blood levels of vWf are independently associated with moderate intensity exercise systolic BP. These findings implicate abnormalities in haemostasis as a possible factor contributing to HRE at moderate intensity.
Publisher: Elsevier BV
Date: 02-2002
Abstract: To identify patients with poor tissue factor pathway inhibitor (TFPI) response to heparin and observe any association with increased risk of excessive coagulation activation, morbidity, or mortality. Prospective, observational cohort study. University hospital. Patients (n = 96) undergoing cardiopulmonary bypass for various types of surgery. None. TFPI antigen and activity were determined in patients before and after heparin administration, before cardiopulmonary bypass for cardiac surgery. The clinical progress of each patient was recorded. Median levels of TFPI activity were 0.98 U/mL (interquartile range, 0.83 to 1.14 U/mL) preheparin and 2.34 U/mL (2.18 to 2.54 U/mL) postheparin (p < 0.0001), representing a median 2.3-(2.1- to 2.8-) fold increase. Median TFPI antigen levels were 92.4 ng/mL (73.0 to 119.5 ng/mL) preheparin and 422.9 ng/mL (398.7 to 501.6 ng/mL) postheparin (p < 0.0001), representing a median 4.6-fold (3.6- to 6.2-fold) increase. Two patients had low (<300 ng/mL) postheparin levels of TFPI antigen that were not associated with low functional TFPI or adverse clinical outcome. Fourteen patients showed a low ratio of increased functional TFPI postheparin all had a ratio of TFPI antigen increase of at least 3-fold. The TFPI response to heparin is heterogenous. Two nonresponders were identified, with low postheparin levels of TFPI antigen, who did not suffer adverse clinical outcomes.
Publisher: Wiley
Date: 08-2001
DOI: 10.1046/J.1365-2141.2001.02923.X
Abstract: The association between antiphospholipid antibodies and an increased risk of thrombosis in antiphospholipid syndrome (aPS) patients is probably caused by numerous mechanisms, including the effects of antibodies to phospholipid-binding proteins such as beta(2)-glycoprotein I and prothrombin. In this study, we investigated the inhibition of tissue factor pathway inhibitor (TFPI) in 33 patients with primary antiphospholipid syndrome (PAPS). TFPI was measured in PAPS patients using an amidolytic assay, dependent on the generation of activated factor X (Fxa), and this was compared with 55 healthy subjects. Functional levels of TFPI (mean +/- SD) were significantly lower in PAPS patients (0.89 +/- 0.37 U/ml) than the control group (1.05 +/- 0.15 U/ml) (P = 0.02). The difference was caused by a subset of five patients who had TFPI levels below the lower 99% confidence interval of the normal reference range, representing increased FXa generation in the assay system. IgG fractions were isolated from these five patients and five control subjects, then incorporated into normal plasma to measure FXa generation in the TFPI assay system. FXa generation was increased when polyclonal rabbit anti-human TFPI IgG (P < 0.0001) or PAPS IgG (P = 0.0001) were added to normal plasma, demonstrating inhibition of TFPI. The apparent anti-TFPI activity demonstrated in the five subjects with PAPS in this study may represent a significant new mechanism for thrombosis in patients with aPS, as it implies that increased tissue factor FVIIa-mediated thrombin generation might occur.
Publisher: Elsevier BV
Date: 12-2008
DOI: 10.1016/J.THROMRES.2008.03.024
Abstract: Patients with chronic kidney disease exhibit features of a hypercoagulable state and have endothelial dysfunction, which may contribute to their increased cardiovascular risk. We examined the relationship between coagulation activation and vascular function in patients with chronic kidney disease. We measured parameters of the tissue factor pathway of blood coagulation (tissue factor, factor VIIc and factor X) natural inhibitors (tissue factor pathway inhibitor, protein C, free and total protein S, antithrombin III) and markers of coagulation activation (thrombin-antithrombin complexes, prothrombin fragment 1+2) in 66 stage 4 chronic kidney disease patients and 36 healthy controls. Their relationship with markers of vascular function (flow mediated dilatation, soluble E-selectin and thrombomodulin) and a mediator of inflammation (interleukin-6) was determined. Up-regulation of the tissue factor pathway (increased tissue factor and factor VIIc), increased prothrombin fragment 1+2 and significant reductions in antithrombin III and the ratio of free protein S: total protein S were found in patients compared to healthy controls. Increased tissue factor antigen was significantly and independently correlated with creatinine and interleukin-6 (P<0.001). Factor X and antithrombin III were both reduced in chronic kidney disease and correlated (r=0.58 P<0.001). Changes in coagulation and anti-coagulation were independent of all measures of endothelial function. Significant activation of the TF pathway of coagulation and depletion or reduction of some natural anticoagulants in chronic kidney disease was correlated with the degree of renal dysfunction, but not correlated with the abnormalities of vascular function. These data are consistent with a hypercoagulable state in chronic kidney disease that may be independent of endothelial based regulation but associated with an inflammatory state.
Publisher: Georg Thieme Verlag KG
Date: 04-2007
Abstract: Technology in hemostasis laboratories has evolved enormously during the last 30 years. Although many scientists and clinicians will remember the traditional tilt-tube techniques to screen for coagulation abnormalities and to monitor anticoagulant therapy, the hemostasis laboratory today uses a variety of modern technologies. These include flow cytometry, chromogenic assays, molecular typing (e.g., polymerase chain reaction), immunologic assays (e.g., enzyme-linked immunosorbent assays), functional assays of specific coagulation proteins, and platelet function analyzers. Although these advances in technology have resulted in greater capability, productivity, sensitivity, specificity, and ultimately, improvement in the clinical care of patients, controversies and limitations remain. This article highlights new and emerging technologies in hemostasis and discusses whether they have improved or are likely to improve laboratory diagnostics by specifically addressing the following: (1) Can new technologies help predict likelihood of thrombosis recurrence? (2) Has an understanding of the role of A Disintegrin-like And Metalloprotease with Thrombo Spondin type 1 motifs (ADAMTS13) in microangiopathy resulted in improved diagnostic methods for this disorder? (3) Does thrombelastography allow better definition of bleeding risk than conventional hemostasis assays, especially in settings of acute hemostatic pathology?
Publisher: Georg Thieme Verlag KG
Date: 16-03-2013
Abstract: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that can affect any part of the body, including the skin, liver, kidneys, and blood. Thrombosis is a frequent manifestation in SLE, contributing significantly to patient morbidity and mortality, although the precise mechanism(s) of how this occurs remains unclear. Fibrinolysis is the physiologic process of thrombus digestion and provides an important balance to hemostasis. This process is triggered upon vessel injury with the release of tissue-type plasminogen activator (t-PA) from endothelial cells. The central component of the fibrinolytic pathway is plasminogen, a zymogen that is converted to plasmin by t-PA. Plasminogen lasmin is absorbed into the developing thrombus and digests fibrinogen and fibrin within the hemostatic plug to prevent excessive clot formation. Abnormalities of the fibrinolytic pathway are associated either with the development of thrombosis (impaired fibrinolysis) or, to a lesser extent, bleeding (excessive fibrinolysis). Indeed, impaired fibrinolysis has been reported in patients with SLE and may contribute to both the development of hypercoagulability and an increased risk of thrombosis. Here we discuss the role of impaired fibrinolysis and its contribution to hypercoagulability and thrombosis in SLE.
Publisher: Georg Thieme Verlag KG
Date: 06-11-2015
Abstract: Tissue factor pathway inhibitor (TFPI) is the major physiological regulator of tissue factor (TF)-induced blood coagulation. TFPI inhibits the TF-activated factor VII (FVIIa) complex in an activated factor X (FXa)-dependent manner, helping to control thrombin generation and ultimately fibrin formation. The importance of TFPI is demonstrated in models of hemophilia where lower levels of FVIII or FIX are insufficient to overcome its inhibitory effect, resulting in a bleeding phenotype. There are two major isoforms in vivo TFPIα contains three Kunitz-type inhibitory domains (designated K1, K2, and K3), is secreted by endothelial cells and requires protein S to enhance its anticoagulant activity. In contrast, TFPIβ contains only the K1 and K2 domains, but it is attached to the endothelial surface via a glycosylphosphatidylinositol anchor. This review will initially provide a brief history of the major discoveries related to TFPI, and then discuss new insights into the physiology of TFPI, including updates on its association with protein S and FV, as well as the current understanding of its association with disease.
Publisher: SAGE Publications
Date: 12-10-2011
Abstract: Thrombosis is a frequent manifestation in patients with systemic lupus erythematosus (SLE), although precise mechanisms remain unclear. This study investigated whether the major physiological trigger of blood coagulation, the tissue factor (TF) pathway, was altered in SLE patients. Furthermore, we investigated potential associations between the TF pathway, the presence of antiphospholipid (APL) antibodies and other abnormalities present in SLE. A total of 101 participants (40 SLE patients and 61 age- and sex-matched controls) were recruited from Tasmania, Australia. Markers of the TF pathway, hypercoagulability, inflammation and endothelial cell damage were measured in plasma. Serum levels of APL antibodies (anti-cardiolipin antibodies [ACL], lupus anticoagulants [LAC], anti-beta2-glycoprotein-1 [anti-β2GP1] and anti-prothrombin antibodies) were also determined. Despite similar TF and TF pathway inhibitor (TFPI) total antigen levels, SLE patients had significantly increased levels of TFPI free antigen (patients vs controls mean ± SD) (11.6 ± 0.9 ng/mL vs 6.4 ± 0.4 ng/mL p 0.001) but significantly reduced TFPI activity (0.66 ± 0.07 U/mL vs 1.22 ± 0.03 U/mL p 0.001), compared with healthy controls. Anti-TFPI activity, designated as the ability of isolated IgG fractions to inhibit TFPI activity in normal plasma, was detected in 19/40 (47.5%) of SLE patients and 3/40 (7.5%) of healthy controls. The significant reduction in TFPI activity in SLE patients reflects impaired functional control of the TF pathway. Moreover, SLE patients with a history of thrombosis demonstrated higher levels of TFPI activity compared with patients without a previous thrombotic event (0.97 ± 0.07 U/mL vs 0.53 ± 0.14 U/mL p = 0.0026). Changes to the TF pathway were not associated with manifestations of SLE such as inflammation or endothelial cell damage. The results from this study suggest hypercoagulability in SLE may (in part) be due to reduced TFPI activity, a mechanism that appears to be independent of other abnormalities in SLE.
Publisher: Georg Thieme Verlag KG
Date: 11-2018
Publisher: Elsevier BV
Date: 12-2009
Publisher: American Association for Laboratory Animal Science
Date: 08-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2007
Publisher: Informa UK Limited
Date: 12-2009
Abstract: Thrombophilia refers to the increased tendency to form blood clots (thrombosis), which is a major cause of morbidity and mortality. Thrombosis is associated with various chronic conditions such as cancer, diabetes, renal disorders, and cardiovascular disease. The incidence and associated complications of thrombosis are likely to increase significantly in the next few decades because of aging populations. Regular exercise has been proposed to decrease the risk of developing thrombosis, although there are inconsistent data from studies investigating its effects, with reports of both increased and decreased thrombotic risk across a variety of subject cohorts. Confounders such as age, gender, hormonal variations, physical activity, underlying disease and treatment, and body composition also contribute to the difficulty in assessing and defining the precise effects of exercise in preventing thrombotic events. However, there is evidence suggesting that physical activity is beneficial for reducing thrombotic risk in younger in iduals and those with chronic conditions. This article aims to summarize the known risk factors for thrombosis and briefly review the benefits of exercise in the general population. Furthermore, this article highlights the additional factors in a cohort of in iduals that would (at first) appear unlikely to be at risk of thrombosis--elite athletes.
Publisher: Georg Thieme Verlag KG
Date: 10-2009
Abstract: Systemic lupus erythematosus (SLE) is a potentially fatal multiorgan inflammatory disease that primarily affects females. Due to the heterogeneity of clinical manifestations and lack of laboratory tests that are both specific and sensitive for the disease, diagnosis of SLE can often be difficult. Although the precise etiology remains to be fully elucidated, it is probable that various environmental, genetic, and hormonal factors contribute to the development of the disease. Patients with SLE have an increased risk for premature thrombosis and/or atherosclerosis, with up to half experiencing a thrombotic event. Furthermore, antiphospholipid antibodies probably play a key role in the development of thrombosis by affecting various hemostatic protein interactions with phospholipids and cell surfaces as well as platelet function. Despite recent advances in knowledge related to the factors that contribute to the pathophysiology of SLE, numerous challenges related to earlier diagnosis as well as the prediction and prevention of thrombotic events remain to be fully addressed.
Publisher: Georg Thieme Verlag KG
Date: 04-2008
Abstract: The antiphospholipid syndrome (APS) is characterized by clinical manifestations such as venous and arterial thrombosis, thrombocytopenia and/or recurrent pregnancy loss, as well as the persistent presence of laboratory markers of antiphospholipid (aPL) antibodies detected in laboratory assays. Though it is generally accepted that aPL antibodies, such as anticardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI), and lupus anticoagulants (LA) contribute to the pathogenesis of APS, precise mechanism(s) are yet to be fully described. It is probable that aPL antibodies bind to a range of cellular targets (e.g., platelets, endothelial cells, and monocytes), leading to thrombosis and obstetric complications. There is now increasing evidence that alterations to the tissue factor (TF) pathway of blood coagulation contribute toward hypercoagulability in patients with aPL antibodies. This article reviews current evidence that suggests changes and/or interference to the major pathway of blood coagulation may represent a novel mechanism that contributes to the development of APS.
Publisher: Springer Science and Business Media LLC
Date: 13-06-2013
Publisher: Georg Thieme Verlag KG
Date: 03-09-2020
Abstract: The proinflammatory cytokine storm associated with coronavirus disease 2019 (COVID-19) negatively affects the hematological system, leading to coagulation activation and endothelial dysfunction and thereby increasing the risk of venous and arterial thrombosis. Coagulopathy has been reported as associated with mortality in people with COVID-19 and is partially reflected by enhanced D-dimer levels. Poor vascular health, which is associated with the cardiometabolic health conditions frequently reported in people with severer forms of COVID-19, might exacerbate the risk of coagulopathy and mortality. Sedentary lifestyles might also contribute to the development of coagulopathy, and physical activity participation has been inherently lowered due to at-home regulations established to slow the spread of this highly infectious disease. It is possible that COVID-19, coagulation, and reduced physical activity may contribute to generate a “perfect storm,” where each fuels the other and potentially increases mortality risk. Several pharmaceutical agents are being explored to treat COVID-19, but potential negative consequences are associated with their use. Exercise is known to mitigate many of the identified side effects from the pharmaceutical agents being trialled but has not yet been considered as part of management for COVID-19. From the limited available evidence in people with cardiometabolic health conditions, low- to moderate-intensity exercise might have the potential to positively influence biochemical markers of coagulopathy, whereas high-intensity exercise is likely to increase thrombotic risk. Therefore, low- to moderate-intensity exercise could be an adjuvant therapy for people with mild-to-moderate COVID-19 and reduce the risk of developing severe symptoms of illness that are associated with enhanced mortality.
Publisher: Informa UK Limited
Date: 2009
DOI: 10.3109/09537100903267517
Abstract: Conflicting information is available regarding patient preparation with respect to the fasting and feeding states prior to blood collection in order to conduct platelet aggregation tests. Some literature suggests avoidance of only high-fat foods and allowance of non-fat foods and clear liquids others suggest a fast of 8-10 hours. We conducted a study in 16 healthy subjects aged 44.0 +/- 12.7 (mean +/- SD) years to investigate and compare the effects of fasting and a high-carbohydrate low-fat meal on measures of platelet aggregation. Blood s les collected after an overnight fast of 10-12 hours and those collected at 40 and 120 minute postprandially (post-high-carbohydrate low-fat meal 1900 kJ energy 69, 16 and 15% of energy from carbohydrate, protein and fat, respectively), were tested for platelet aggregation in response to adenosine diphosphate. There was a significant reduction in maximum aggregation and area under the aggregation curve from fasting to 120 minute post meal (overall p < 0.001). Serum triglyceride concentrations did not change significantly from fasting to postprandial state (p = 0.53). Although there was a significant association between serum insulin, plasma glucose and measures of platelet aggregation, correcting for the effects of these metabolic parameters did not alter the results, providing evidence that other, currently unknown, factors associated with food consumption affect postprandial platelet aggregation. We propose that protocols for control of pre-analytical variables in platelet aggregation studies should make a fasting s le mandatory rather than "preferable" unless the objective of the study is to measure acute effects in response to a medication or food.
Publisher: Springer Science and Business Media LLC
Date: 18-11-2013
DOI: 10.1007/S00421-012-2543-1
Abstract: Aortic pulse wave velocity (PWV) and augmentation index (AIx) are independent predictors of cardiovascular risk and mortality, but little is known about the effect of air temperature changes on these variables. Our study investigated the effect of exposure to whole-body mild-cold on measures of arterial stiffness (aortic and brachial PWV), and on central haemodynamics [including augmented pressure (AP), AIx], and aortic reservoir components [including reservoir and excess pressures (P ex)]. Sixteen healthy volunteers (10 men, age 43 ± 19 years mean ± SD) were randomised to be studied under conditions of 12 °C (mild-cold) and 21 °C (control) on separate days. Supine resting measures were taken at baseline (ambient temperature) and after 10, 30, and 60 min exposure to each experimental condition in a climate chamber. There was no significant change in brachial blood pressure between mild-cold and control conditions. However, compared to control, AP [+2 mmHg, 95 % confidence interval (CI) 0.36-4.36 p = 0.01] and AIx (+6 %, 95 % CI 1.24-10.1 p = 0.02) increased, and time to maximum P ex (a component of reservoir function related to timing of peak aortic in-flow) decreased (-7 ms, 95 % CI -15.4 to 2.03 p = 0.01) compared to control. Yet there was no significant change in aortic PWV (+0.04 m/s, 95 % CI -0.47 to 0.55 p = 0.87) or brachial PWV (+0.36 m/s -0.41 to 1.12 p = 0.35) between conditions. We conclude that mild-cold exposure increases central haemodynamic stress and alters timing of peak aortic in-flow without differentially affecting arterial stiffness.
Publisher: Elsevier BV
Date: 07-1997
DOI: 10.1016/S0049-3848(97)00124-2
Abstract: β-lactams are the cornerstone of empiric and targeted antibiotic therapy for critically ill patients. Recently, there have been calls to use β-lactam therapeutic drug monitoring (TDM) within 24-48 hours after the initiation of therapy in critically ill patients. In this article, we review the dynamic physiology of critically ill patients, β-lactam dose response in critically ill patients, the impact of pathogen minimum inhibitory concentration (MIC) on β-lactam TDM, and pharmacokinetics in critically ill patients. Additionally, we highlight available clinical data to better inform β-lactam TDM for critically ill patients. We retrospectively analyzed patients admitted for sepsis or septic shock at a single academic medical center who were treated with β-lactam antibiotics. Indexed studies in PubMed in English language were selected for review on topics relative to critical care physiology, β-lactams, pharmacokinetics harmacodynamics, TDM, and antibiotic susceptibility. We reviewed potentially related studies on β-lactams and TDM and summarized their design, patients, and results. This is a synthetic, nonsystematic, review. In the retrospective analysis of patients treated with β-lactam antibiotics, approximately one-third of patients received less than 48 hours of β-lactam therapy. Of those who continued beyond 48 hours, only 13.7% had patient-specific factors (augmented renal clearance, fluid overload, morbid obesity, and/or surgical drain), suggesting a potential benefit of β-lactam TDM. These data indicate that a strategy of comprehensive β-lactam TDM for critically ill patients is unwarranted as it has not been shown yet to improve patient-oriented outcomes. This review demonstrates that β-lactam TDM in the ICU, while laudable, layers ambiguous β-lactam exposure thresholds upon uncertain/unknown MIC data within a dynamic, unpredictable patient population for whom TDM results will not be available fast enough to significantly affect care. Judicious, targeted TDM for those with risk factors for β-lactam over- or underexposure is a better approach but requires further study. Clinically, choosing the correct antibiotic and dosing β-lactams aggressively, which have a wide therapeutic index, to overcome critical illness factors appears to give critically ill patients the best likelihood of survival.
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.THROMRES.2014.05.038
Abstract: Plant-derived and endogenous vanilloid-like agents exert their effects on cells through transient receptor potential vanilloid-1 (TRPV1). Little is known about the effects of these agents on platelet aggregation. We investigated the effect of various vanilloid-like agents on in-vitro platelet aggregation and tested whether this action is mediated through TRPV1. Understanding the mechanism of action of these compounds in platelets is important in that these compounds may be developed as novel anti-platelet agents. The effects of plant-derived (capsaicin dihydrocapsaicin, DHC) and endogenous vanilloid-like agents (N-oleoyldopamine, OLDA N-arachidonoyl-dopamine, NADA) on platelet aggregation were investigated using ADP (5, 10μM), collagen (4, 8μg/mL) and arachidonic acid (AA, 300, 400μg/mL) as agonists. The direct effects of these agents on platelet viability were also determined using an LDH release assay. Capsaicin, OLDA and NADA inhibited ADP-induced platelet aggregation in a concentration-dependent manner. OLDA and NADA, but not capsaicin and DHC, inhibited collagen-induced aggregation, whereas AA-induced aggregation was inhibited by capsaicin, DHC and NADA, but not OLDA. Inhibition of aggregation was not due to direct toxicity of these agents towards platelets. The TRPV1 antagonist, SB-452533, did not affect inhibition of ADP-induced platelet aggregation by capsaicin and OLDA. These results demonstrate that the endovanilloids, OLDA and NADA, and plant-derived vanilloid, capsaicin, inhibit ADP-induced platelet aggregation. Collagen-induced aggregation was inhibited only by endovanilloids, whereas AA-induced aggregation was inhibited by capsaicin, DHC and NADA. This inhibition was not due to direct toxic effects of these agents, nor was inhibition of ADP-induced aggregation TRPV1 mediated.
Publisher: Georg Thieme Verlag KG
Date: 19-02-2013
Abstract: Lupus anticoagulants (LAs) are antiphospholipid antibodies that interfere with in vitro phospholipid-dependent clotting tests, but are associated in vivo with significant clinical manifestations such as recurrent pregnancy loss and venous and arterial thrombosis. Although their detection is important for the diagnosis of thrombotic disorders such as the antiphospholipid syndrome, laboratory identification has historically been fraught with many issues. These have included variability in the sensitivity of assays and reagents high false-negative and false-positive detection rates a lack of consensus for the use of mixing tests and, to some extent, lack of compliance with guidelines published by the Lupus Anticoagulant/Antiphospholipid Antibody Scientific Standardization Committee of the International Society on Thrombosis and Haemostasis (ISTH). Since the most recently updated guidelines in 2009, external quality assurance (EQA) programs have conducted surveys to provide a "snapshot" of laboratory practices related to the investigation of LA and to identify problems and monitor improvements in testing for LA. This article will review the impact of the most recently updated ISTH guidelines for LA testing and discuss the findings of recent EQA surveys.
Publisher: Elsevier BV
Date: 02-2013
Publisher: Springer Science and Business Media LLC
Date: 31-05-2017
Publisher: Cold Spring Harbor Laboratory
Date: 08-08-2021
DOI: 10.1101/2021.08.04.21261521
Abstract: The ectopic overexpression of transient receptor potential vanilloid-1 (TRPV1) has been detected in numerous solid cancers including breast, prostate, pancreatic, and tongue epithelium cancer. However, the expression of TRPV1 in hematological malignancies remains unknown. Here we show through in silico analysis that elevated TRPV1 mRNA expression occurs in a range of hematological malignancies and present an optimized flow cytometry method to rapidly assess TRPV1 protein expression for both cell lines and primary patient s les. Three anti-TRPV1 antibodies were evaluated for intracellular TRPV1 detection using flow cytometry resulting in an optimized protocol for the evaluation of TRPV1 in hematological malignant cell lines and patients’ peripheral blood mononuclear cells (PBMC). Overexpression of TRPV1 was observed in THP-1 (acute monocytic leukemia) and U266B1 (multiple myeloma, MM), but not U937 (histiocytic lymphoma) compared to healthy PBMC. TRPV1 was also detected in all 49 patients (including B-cell non-Hodgkin’s lymphoma (B-NHL), MM and others, and 20 healthy controls. TRPV1 expression was increased in 8% of patients (MM=2, B-NHL=2). In conclusion, we provide an optimized flow cytometry method for routine expression analysis of clinical s les and show that TRPV1 is increased in 8% of patients with hematological malignancies.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2007
Publisher: Georg Thieme Verlag KG
Date: 08-02-2012
Abstract: Blood coagulation in vivo is triggered by the tissue factor (TF) pathway. The major physiological regulator of this pathway is tissue factor pathway inhibitor (TFPI), a Kunitz-type inhibitor that regulates the activity of the TF-factor VIIa complex in a factor Xa-dependent manner, thus controlling the generation of thrombin and ultimately, fibrin. Although some of the in vivo and in vitro effects of TFPI have been described for nearly a century, the bulk of the research that has elucidated the physiology of this inhibitor has only occurred in the past 25 years. Despite this, many questions remain. This review will highlight the recent advances in knowledge related to TFPI, with an emphasis on new insights into its physiology, association with disease, and possible use as a therapeutic anticoagulant.
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.FCT.2014.01.034
Abstract: Carpobrotus rossii (CR) was used by the Aboriginal population and early European settlers both as a food and therapeutic agent. Based on the presence of flavonoids in CR and results from our previous in vitro investigations, this study aimed to determine whether consumption of CR crude leaf extract: (a) affected lipoprotein profile, resting glucose, systolic blood pressure and vascular function, and (b) produced toxic effects (haematological measures, organ weight) in healthy rats. Male Hooded-Wistar rats (~230 g) were supplemented for 4 weeks with CR extract in their drinking water (35 mg/kg body weight daily). CR extract produced a significant decrease (18%, p=0.033) in atherogenic lipoproteins (but not high density lipoprotein). CR supplemented animals showed no signs of haematological toxicity and body and organ weight, daily fluid and food consumption and in vitro vascular responsiveness were similar for both groups. CR also increased (40%, p=0.049) the renal concentration of 3-hydroxy-3-methylglutaric acid (HMG), consistent with HMG-containing CR flavonoids being bioavailable, and therefore possessing the potential to interfere with cholesterol synthesis pathways. CR extract appears to be safe to ingest and may reduce cardiovascular risk.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2006
Publisher: Elsevier
Date: 2017
DOI: 10.1016/BS.APHA.2017.01.002
Abstract: Transient receptor potential vanilloid-1 (TRPV1) is a member of the TRP family of channels that are responsible for nociceptive, thermal, and mechanical sensations. Originally associated exclusively with sensory neurons, TRPV1 is now known to be present in almost all organs, including cells of the immune system, where TRPV1 has been shown to play a pivotal role in inflammation and immunity. Monocytes, macrophages, and dendritic cells express TRPV1, with both mouse and human studies suggesting that TRPV1 activation protects against endotoxin-induced inflammation. In contrast, TRPV1 (and other TRP channels) appears to be required for T-cell receptor activation by mitogens. Additionally, studies in cell lines derived from hematological and other malignancies suggest altered expression/function of TRPV1 might serve as a target for novel cytotoxic therapies.
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.NUT.2010.10.014
Abstract: Nutritional compounds that potentially limit inflammation and tissue factor expression may decrease the progression of chronic kidney disease (CKD) and associated cardiovascular disease. This project aimed to determine the effect of curcumin, bovine colostrum, and fish oil on inflammatory cytokine and tissue factor procoagulant activity of peripheral blood mononuclear cells (PBMCs) from patients with CKD before dialysis. Peripheral blood mononuclear cells from patients with CKD before dialysis (n = 13) and age- and sex-matched healthy controls (n = 12) were cultured alone and with low and high doses of the nutritional compounds for 24 h. Cells were cultured with and without lipopolysaccharide. Supernatants were analyzed for tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1, IL-1β, C-reactive protein, and tissue factor procoagulant activity. The production of C-reactive protein, monocyte chemoattractant protein-1, IL-6, and IL-1β by PBMCs was inhibited by low- and high-dose fish oil in the CKD group (P < 0.05). Curcumin decreased secretion of IL-6 (P = 0.015) and IL-1 β (P = 0.016). Curcumin was more effective than colostrum at decreasing the procoagulant activity of PBMCs in the CKD and control groups (P < 0.019). Fish oil decreased inflammatory cytokine secretion from CKD PBMCs. In addition, the beneficial effects of curcumin were demonstrated in decreasing inflammation in vitro, often to a similar magnitude as fish oil.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2000
DOI: 10.1097/00001721-200006000-00003
Abstract: Tissue factor pathway inhibitor (TFPI) is a Kunitz-type inhibitor that regulates the initiation of tissue factor-mediated coagulation. Recent reports in the literature have described variable results using different methodologies for TFPI measurement. In this study, we used one clotting and two amidolytic methodologies to assess TFPI functional levels. The study groups included normal healthy donors as well as patients with acute hepatitis, diabetes, coronary artery bypass graft operations, deep vein thrombosis, and prior to and during heparin therapy. The aims were to compare the results obtained in normal plasma using different assay systems, to compare TFPI levels in a range of clinical s les, including those previously not determined using a clotting methodology, and to report TFPI levels in patient groups previously not investigated. The results clearly demonstrate poor correlation between functional TFPI values using the different methodologies, highlighting the requirement for standardization.
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1111/JTH.14601
Abstract: Laboratory analyses of blood s les are essential for diagnostics and therapy monitoring of patients with bleeding and thromboembolic diseases. Following publication of the core curriculum for clinical thrombosis and hemostasis, the International Society on Thrombosis and Haemostasis (ISTH) recognized that thrombosis and hemostasis laboratory specialists require distinct competencies that differ from medical doctors working clinically with patients. To address this gap the ISTH formed a working group of international hemostasis and thrombosis laboratory specialists to develop an evidence-based core curriculum for laboratory specialists. This research sought consensus from the international community on core competencies required for laboratory specialists in thrombosis and hemostasis. A draft list of 64 competencies was developed and an online stakeholder survey was circulated electronically to 15 302 ISTH members and contacts in the wider international community. The results were analyzed and used to develop the final approved core curriculum. Three hundred and thirty responses contained meaningful data, with broad international representation of specialists. No draft competencies were excluded, and 58 were rated as "does" or "shows how." The Leik measure of consensus for most competences was "moderate" (n = 30) or "fair" (n = 32). The development of an international core curriculum for laboratory specialists provides a foundation for the development and enhancement of education and quality management of the laboratory. Although there is no formal designation for laboratory specialists, international governing bodies and regulatory organizations are encouraged to consider the diagnostic core curriculum for development and accreditation of more standardized educational programs and formal assessment across jurisdictions.
Publisher: Springer Science and Business Media LLC
Date: 25-04-2017
DOI: 10.1007/S10067-017-3652-3
Abstract: B cells are known to play a dominant pathogenic role in autoimmune conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. In recent times, the chemokine receptor CCR6 and its cognate ligand CCL20 have been shown to play a role in the fundamental kinetics of germinal centres and B cell responses. As CCR6 is found on B cells and is upregulated after activation, we investigated the expression of CCR6 on naive, pre-germinal centre (GC), GC lasma cell and memory B cells in peripheral B cells of SLE patients and healthy controls using flow cytometry. Pre-germinal centre B cells are found in lower proportions and the expression of CCR6 is increased on B cells of SLE patients, suggesting a role for the chemokine pair in the pathogenesis of the disease. Further studies are needed to explore these preliminary results.
Publisher: Wiley
Date: 21-10-2013
DOI: 10.1002/DDR.21102
Publisher: Georg Thieme Verlag KG
Date: 02-2009
Abstract: Thrombin plays an important role in hemostasis through its multiple functions across blood coagulation, platelet activation, and fibrinolysis. The measurement of thrombin generation is therefore viewed as a potentially useful test that could be applied to the screening, monitoring, and/or diagnosis of hemostatic abnormalities. Indeed, advances in thrombin generation assays have created significant interest and debate as to whether they may provide a more physiologically relevant testing system than do traditional coagulation tests. A variety of thrombin generation assays, including commercially available systems, have been investigated for their correlation with hypocoagulable and hypercoagulable states. Although there is an extensive body of literature that has investigated the application of thrombin generation assays, some limitations remain. These include poor standardization of reagents and methods and a lack of large prospective studies that demonstrate clear relationships between thrombin generation with bleeding and thrombosis phenotypes, as well as with monitoring anticoagulation. Whether thrombin generation assays become more "useful" than "hype" will require well-designed, large, prospective multicenter trials using standardized methods.
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.THROMRES.2012.05.022
Abstract: To date there is minimal data available on D-Dimer levels at different stages of pregnancy. We prospectively measured D-Dimer levels in 632 consecutive pregnant women from March 2007 to January 2009. The median age of the participants was 31 years (range 18-42) with a median weight of 78 kilograms (range 46-137). All subjects were investigated during each trimester with two different immunoturbidimetric assays D-Dimer PLUS and INNOVANCE D-Dimer. D-Dimer levels were determined using a Sysmex® CA 1500 analyser. Our data demonstrate that D-Dimer levels in pregnancy show different patterns of rise within the first trimester, depending on the assay used D-Dimer PLUS=0.88 (SD: mean ratio), INNOVANCE D-Dimer=0.72 (SD: mean ratio). Furthermore, the rise in mean results was greater for the INNOVANCE D-Dimer assay compared to the D-Dimer PLUS assay as shown by the ratio of third to first trimester results of 3.68 and 1.96 respectively. Both D-Dimer assays demonstrated moderate levels of intra-subject variability, with overall mean CVs of 16.5% (D-Dimer PLUS) and 16.9% (INNOVANCE D-Dimer). Furthermore, we studied the association between D-Dimer levels and occurrence of diseases of pregnancy. For both assays, there was no consistently interpretable evidence of an association between raised mean D-Dimer levels or rising D-Dimer levels and any of the diseases or conditions associated with pregnancy. Our data suggest that the INNOVANCE D-Dimer assay increases significantly with the advancement of pregnancy, and is more sensitive than D-Dimer PLUS assay in the pregnant population.
Publisher: Wiley
Date: 22-06-2009
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000445437
Abstract: The effect of the plant-derived vanilloid, capsaicin (CAP), on the metabolic activity of THP-1, U266B1 and U937 hematological malignancy cells was determined. CAP reduced metabolic activity in a concentration-dependent manner in the three cell lines. A biphasic effect was observed on THP-1 cells (EC sub /sub : IC sub /sub (95% CI) 32.9 (19.9-54.3)/219 (144-246) µmol/l). U266B1 cells were more resistant to CAP than THP-1 and U937. Metabolic activity was significantly inhibited by CAP in U937 compared to U266B1 cells (IC sub /sub : 197 versus 431 µmol/l, respectively, p 0.008). Transient receptor potential vanilloid-1 (TRPV1) and CB1 antagonists (SB452533 and AM251, respectively) suppressed the CAP-induced increase in THP-1 cell metabolic activity (p 0.001). AM251 and SB452533 appeared to act as partial agonists and displayed a synergistic effect with CAP in U937 cells. CAP inhibits the metabolic activity of malignant hematological cells through non-TRPV1-dependent mechanisms.
Publisher: Informa UK Limited
Date: 10-01-2018
DOI: 10.1080/17461391.2017.1420237
Abstract: Exercise has been demonstrated to have considerable effects upon haemostasis, with activation dependent upon the duration and intensity of the exercise bout. In addition, markers of coagulation and fibrinolysis have been shown to possess circadian rhythms, peaking within the morning (0600-1200 h). Therefore, the time of day in which exercise is performed may influence the activation of the coagulation and fibrinolytic systems. This study aimed to examine coagulation and fibrinolytic responses to short-duration high-intensity exercise when completed at different times of the day. Fifteen male cyclists (VO
No related grants have been discovered for Murray Adams.