ORCID Profile
0000-0003-2455-3155
Current Organisations
Royal College of Pathologists of Australasia
,
Royal Australasian College of Physicians
,
Northern Health
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2018
Publisher: Wiley
Date: 03-2016
DOI: 10.1111/IMJ.12992
Abstract: There is a paucity of evidence supporting the necessity or duration of Pneumocystis jirovecii and antiviral prophylaxis as well as revaccination following autologous stem cell transplant (ASCT). A survey aimed at evaluating these policies was distributed to 34 ASCT centres across Australasia. The 26 survey respondents demonstrated significant heterogeneity in their infection prophylaxis and revaccination strategy post-transplant despite the availability of consensual guidelines.
Publisher: Elsevier BV
Date: 02-2017
Publisher: MDPI AG
Date: 13-10-2022
DOI: 10.3390/JPM12101711
Abstract: Abnormal coagulation and fibrinolysis contributes to the respiratory distress syndrome in COVID-19. We aimed to explore the association of impaired fibrinolytic potential with disease severity and oxygen requirement in hospitalized patients. Adults admitted to hospital with confirmed COVID-19 infection between 1–31 January 2022 were included, corresponding to the first Omicron outbreak in Melbourne, Victoria. The first citrated plasma s le requested within 24 h of the patient’s presentation was obtained and analyzed by the overall hemostatic potential (OHP) assay, a spectrophotometric assay in which fibrin formation (triggered by small amounts of thrombin (OCP)) and fibrinolysis (by the addition of thrombin and tissue plasminogen activator (OHP and OFP%)) were simultaneously measured. There were 266 patients (median 72 years, 52.9% male), of which 49.6% did not require oxygen therapy. COVID-19 severity and requirement for oxygen was significantly associated with higher OCP, OHP, and lower OFP%. Vaccinated in iduals compared with non-vaccinated in iduals had significantly lower OHP (16.5 vs. 23.1, p = 0.015) and higher OFP (72.0% vs. 65.1%, p = 0.005), as well as significantly lower AST, ferritin, LDH, CRP, and D-dimer. A multivariate model containing OHP was constructed with the outcome of oxygen requirement, with c-statistic of 0.85 (95%CI 0.81–0.90). In this pilot study, we show a significant correlation between OHP results and requirement for oxygen supplementation in hospitalized patients during a period dominated by the Omicron variant. The results were incorporated into a multivariate model that predicted for oxygen requirement, with high discriminative ability.
Publisher: Wiley
Date: 09-2017
DOI: 10.1111/IMJ.13525
Abstract: Venous thromboembolism (VTE) is a major cause of morbidity and mortality with significant heterogeneity in its management, both within our local practice and in international guidelines. To provide a holistic evaluation of 'real-world' Australian experience in the warfarin era, including how we compare to international guidelines. Retrospective evaluation of VTE from July 2011 to December 2012 at two major hospitals in Melbourne, Australia. These results were compared to recommendations in the international guidelines. A total of 752 episodes involving 742 patients was identified. Contrary to international guidelines, an unwarranted heritable thrombophilia screen was performed in 22.0% of patients, amounting to a cost of AU$29 000. The duration of anticoagulation was longer compared to international recommendations, although the overall recurrence (3.2/100 person-years) and clinically significant bleeding rates (2.4/100 person-years) were comparable to 'real-world' data. Unprovoked VTE (hazard ratio 2.06 P = 0.01) was a risk factor for recurrence, and there was no difference in recurrence between major VTE (proximal deep vein thrombosis (DVT) and/or pulmonary embolism) and isolated distal DVT (3.02 vs 3.94/100 person-years P = 0.25). Fourteen patients were subsequently diagnosed with malignancy, and patients with recurrent VTE had increased risk of prospective cancer diagnosis (relative risk 6.68 P < 0.001). While our 'real-world' VTE experience during the warfarin era largely correlates with international guidelines, there remains heterogeneity in the management strategies, including excessive thrombophilia screening and longer duration of anticoagulation. This audit highlights the need for national VTE guidelines, as well as prospective auditing of VTE management, in the direct oral anticoagulant era for future comparison.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-03-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2013
Publisher: Wiley
Date: 24-05-2017
DOI: 10.1111/EJH.12884
Abstract: Venous thromboembolism (VTE) provoked by transient risk factors has traditionally been classified as a single entity with lower risk of recurrence. We evaluated the association between different categories of transient provoking factors and the relative risk of recurrence. Retrospective evaluation of VTE events in non-cancer patients from July 2011 to December 2012 at two tertiary institutions in Australia with a minimum follow-up of 24 months. A total of 747 VTE cases were identified, and following exclusion of cases with mortality within 30 days of presentation (n=26), unprovoked cases (40.2%) had a higher risk of recurrence (4.6 vs 2.3/100 event-years, P=.01). Provoking factors included surgery (40.4%), injury (16.7%), medical-related factors including non-surgical hospitalisation or active infection (22.0%), travel (13.2%) and oestrogen related (6.5%). Air travel had the highest recurrence rate of 5.9/100 event-years, comparable to unprovoked VTE. VTE provoked by surgery showed lower recurrence rate at 1.8/100 event-years (P=.03). 62.5% of patients with provoked VTE recurred with an unprovoked event. Transient provoking factors for VTE are heterogeneous with varying potency and should not be considered a single entity. The high recurrence rate after travel-provoked VTE suggests that it is a "minor," if not negligible provoking factor with higher thrombotic predisposition.
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1002/RTH2.12611
Publisher: Springer Science and Business Media LLC
Date: 16-12-2022
Publisher: Elsevier BV
Date: 09-2015
Publisher: Springer Science and Business Media LLC
Date: 09-03-2018
DOI: 10.1038/S41409-018-0152-2
Abstract: Bortezomib-based induction is often used in transplant-eligible patients with myeloma. The optimal peripheral blood stem cell (PBSC) mobilisation strategy in this context is unclear. We reviewed the efficacy of G-CSF alone (G-alone) vs. G-CSF and cyclophosphamide (G-cyclo: standard dose: 1.5-2 g/m
Publisher: Wiley
Date: 03-06-2018
DOI: 10.1111/VOXS.12435
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.THROMRES.2022.09.006
Abstract: The introduction of direct oral anticoagulants (DOAC) has resulted in a paradigm shift in the management of venous thromboembolism (VTE). We evaluate the impact of the transition to DOAC, over the last decade, on overall VTE clinical outcomes including in first unprovoked major VTEs. A retrospective analysis of all VTE admissions in non-cancer patients from January 2011 to December 2020 at Northern Health, Victoria, Australia. "Warfarin era" included events that occurred between January 2011 and December 2014 and "DOAC era" from January 2016. There were 2687 cases involving 2508 patients (45.9 % males median age 63 years). 98 % were symptomatic and 1261 events (47 %) were unprovoked. 1003 events occurred during the warfarin era (79 % warfarin, 6 % DOAC) and 1479 during the DOAC era (18 % warfarin, 70 % DOAC). While recurrent thrombosis during the acute phase of treatment was comparable, there were fewer recurrences during the long-term preventative phase of treatment in the DOAC era compared to warfarin era (HR 0.602, 95 % CI: 0.393-0.924, p0.020). Clinically significant bleeding events were lower in the DOAC era (HR 0.623, 95 % CI: 0.395-0.985, p = 0.043). A subanalysis of first unprovoked major VTE events (n = 602) demonstrated a significant reduction in recurrent VTE during the long-term preventative phase of treatment in the DOAC era (HR 0.296, 95 % CI: 0.097-0.901, p = 0.032) with no difference in clinically significantly bleeding rates (HR 0.529, 95 % CI 0.219-1.280, p = 0.158) between the eras. Treatment outcomes for VTE appear to have improved over time with reduced rate of thrombotic and clinically significant bleeding complications in the DOAC era.
Publisher: Wiley
Date: 11-2016
DOI: 10.1111/IMJ.13235
Abstract: We retrospectively evaluated the use of computed tomography abdomen and pelvis (CTAP) in febrile neutropenic autologous stem cell transplant (ASCT) and acute myeloid leukaemia (AML) patients. CTAP was more common in ASCT patients (59%) compared with AML (31% P < 0.001). Although abnormal findings were reported in 51%, only 10% resulted in therapy change (addition of anaerobic antibiotic/bowel rest), which would have otherwise been instituted based on clinical grounds. CTAP in these patients rarely provide useful information unsuspected clinically.
Publisher: The Endocrine Society
Date: 18-08-2020
Abstract: As the number of transgender (trans) people (including those who are binary and/or nonbinary identified) seeking gender-affirming hormone therapy rises, endocrinologists are increasingly asked to assist with interpretation of laboratory tests. Many common laboratory tests such as hemoglobin, iron studies, cardiac troponin, and creatinine are affected by sex steroids or body size. We seek to provide a summary of the impact of feminizing and masculinizing hormone therapy on common laboratory tests and an approach to interpretation. Case scenarios discussed include 1) hemoglobin and hematocrit in a nonbinary person undergoing masculinizing hormone therapy 2) estimation of glomerular filtration rate in a trans woman at risk of contrast-induced nephropathy 3) prostate-specific antigen (PSA) in a trans woman and 4) chest pain in a trans man with a cardiac troponin concentration between the reported male and female reference ranges. The influence of exogenous gender-affirming hormone therapy on fat and muscle distribution and other physiological changes determines interpretation of laboratory tests that have sex-specific differences. In addition to affirmative practice to ensure a patient’s name, gender, and pronoun are used appropriately, we propose that once in iduals have commenced gender-affirming hormone therapy, the reference range of the affirmed gender be reported (and specified by treating clinicians) except for PSA or cardiac troponin, which are dependent on organ size. While suggestions may be challenging to implement, they also represent an opportunity to lead best practice to improve the quality of care and experiences of healthcare for all trans people.
Publisher: Wiley
Date: 26-07-2020
DOI: 10.1002/JPPR.1645
Publisher: MDPI AG
Date: 13-09-2022
DOI: 10.3390/JPM12091495
Abstract: Angiotensin converting enzyme 2 (ACE2) is an endogenous negative regulator of the renin-angiotensin system, a key factor in the development of cardiovascular disease (CVD). ACE2 is also used by SARS-CoV-2 for host cell entry. Given that COVID-19 is associated with hypercoagulability, it is timely to explore the potential relationship between plasma ACE2 activity and the coagulation profile. In this cross-sectional study, ACE2 activity and global coagulation assays (GCA) including thromboelastography, thrombin, and fibrin generation were measured in adult healthy controls (n = 123 mean age 41 ± 17 years 35% male) and in patients with cardiovascular risk factors and/or disease (n = 258 mean age 65 ± 14 years 55% male). ACE2 activity was significantly lower in controls compared to patients with cardiovascular risk factors and/or disease (median 0.10 (0.02, 3.33) vs. 5.99 (1.95, 10.37) pmol/mL/min, p 0.001). Of the healthy controls, 48% had undetectable ACE2 activity. Controls with detectable ACE2 had lower maximum litude (p 0.001). In patients with cardiovascular risk factors and/or disease, those in the 3rd tertile were older and male (p = 0.002), with a higher Framingham grade and increased number of cardiovascular risk factors (p 0.001). In conclusion, plasma ACE2 activity is undetectable to very low in young healthy controls with minimal clinically relevant associations to GCA. Patients with cardiovascular risk factors and/or disease have increased plasma ACE2 activity, suggesting that it may be an important biomarker of endothelial dysfunction and atherosclerosis.
Publisher: The Endocrine Society
Date: 15-05-2020
Abstract: The thrombotic effects of estradiol therapy in transgender women are unclear. Global coagulation assays (GCA) may be better measures of hemostatic function compared with standard coagulation tests. To assess the GCA profiles of transgender women in comparison to cisgender controls and to compare how GCA differ between routes of estradiol therapy in transgender women. Cross-sectional case-control study. General community. Transgender women, cisgender male and cisgender female controls. Citrated blood s les were analyzed for (i) whole blood thromboelastography (TEG®5000), (ii) platelet-poor plasma thrombin generation (calibrated automated thrombogram) and (iii) platelet-poor plasma fibrin generation (overall hemostatic potential assay). Mean difference (95% confidence intervals) between groups are presented. Twenty-six transgender women (16 oral estradiol, 10 transdermal estradiol) were compared with 98 cisgender women and 55 cisgender men. There were no differences in serum estradiol concentration (P = 0.929) and duration of therapy (P = 0.496) between formulations. Transgender women demonstrated hypercoagulable parameters on both thromboelastography (maximum litude + 6.94 mm (3.55, 10.33) P & 0.001) and thrombin generation (endogenous thrombin potential + 192.62 nM.min (38.33, 326.91) P = 0.009 peak thrombin + 38.10 nM (2.27, 73.94) P = 0.034) but had increased overall fibrinolytic potential (+4.89% (0.52, 9.25) P = 0.024) compared with cisgender men. No significant changes were observed relative to cisgender women. Route of estradiol delivery or duration of use did not influence the GCA parameters. Transgender women on estradiol therapy demonstrated hypercoagulable GCA parameters compared with cisgender men with a shift towards cisgender female parameters. Route of estradiol delivery did not influence the GCA parameters.
Publisher: Springer Science and Business Media LLC
Date: 24-02-2021
DOI: 10.1007/S11239-021-02400-Y
Abstract: Global coagulation assays (GCAs) may provide a more comprehensive in idual hemostatic profiling. We aim to evaluate GCAs (thromboelastography, thrombin generation) in healthy controls, and correlate results with age, gender, lipid status, tissue factor pathway inhibitor (TFPI) and P-selectin. Blood s les were collected from healthy controls (> 18 years of age) not taking anticoagulation or antiplatelet agents and without known cardiovascular disease. Thromboelastography (TEG) was performed on citrated whole blood while calibrated automated thrombogram (CAT), P-selectin (endothelial marker) and TFPI (principle inhibitor of tissue factor-initiated coagulation) were performed on platelet-poor plasma. 153 healthy controls (mean age 42 years, 98 females (64%)) were recruited. Female controls demonstrated more hypercoagulable TEG and CAT parameters while those over 50 years of age demonstrated more hypercoagulable TEG parameters despite comparable thrombin generation. Paradoxically, in iduals with "flattened" thrombin curves (lower velocity index (rate of thrombin generation) despite preserved endogenous thrombin potential (amount of thrombin)) were more likely to be male (49% vs 20%, p = 0.003) with increased low-density lipoprotein cholesterol (3.3 vs 2.6 mmol/L, p = 0.003), P-selectin (54.2 vs 47.3 ng/mL, p = 0.038) and TFPI (18.7 vs 8.6 ng/ml, p = 0.001). In addition to reduced velocity index and thrombin peak, controls in the highest TFPI tertile also demonstrated a poorer lipid profile. GCAs can detect subtle changes of the hemostatic profile. Interestingly, reduced thrombin generation was paradoxically associated with increased cardiovascular risk factors, possibly attributable to increased TFPI. This finding may suggest compensation by the coagulation system in response to endothelial activation and represent a biomarker for early cardiovascular disease. A larger prospective study evaluating these assays in the cardiovascular disease population is ongoing.
Publisher: MDPI AG
Date: 14-07-2022
DOI: 10.3390/JPM12071140
Abstract: Cardiovascular disease remains the leading cause of death in the era of modern medicine despite major advancements in this field. Current available clinical surrogate markers and blood tests do not adequately predict in idual risk of cardiovascular disease. A more precise and sophisticated tool that can reliably predict the thrombosis and bleeding risks at an in idual level is required in order for clinicians to confidently recommend early interventions with a favorable risk–benefit profile. Critical to the development of this tool is the assessment and understanding of Virchow’s triad and its complex interactions between hypercoagulability, endothelial dysfunction and vessel flow, a fundamental concept to the development of thrombosis. This review explores the pathophysiology of cardiovascular disease stemming from the triad of factors and how in idualized risk assessment can be improved through the multimodal use of tools such as global coagulation assays, endothelial biomarkers and vessel flow assessment.
Publisher: Wiley
Date: 04-09-2022
DOI: 10.1111/IMJ.15696
Abstract: The heterogeneity of inpatient pulmonary embolism (PE) presentations may lead to computed tomography pulmonary angiograms (CTPA) being over‐requested. Current clinical predictors for PE, including Wells criteria and Pulmonary Embolism Rule‐out Criteria (PERC), have predominantly focussed on outpatient and emergency department populations. To determine the clinical indicators for ordering inpatient CTPA and the predictors of positive scans for PE. Consecutive inpatient CTPA (performed h after admission) from January 2017 to December 2017 were retrospectively reviewed. Variables including baseline characteristics, vital signs and risk factors for PE were extracted. A total of 312 CTPA was reviewed (average patient age 67 years 46% male) and 36 CTPA were positive for PE (11.5%). The average time to inpatient CTPA request was 7 days. Clinical indicators associated with positive scans were hypoxia (odds ratio (OR) 2.4 95% confidence interval (CI) 1.1–5.6), tachypnoea (OR 2.5 95% CI 1.2–6.0), recent surgery or immobilisation (OR 2.7 95% CI 1.2–6.4), S1Q3T3 pattern on electrocardiogram (ECG OR 7.2 95% CI 1.4–35.7) and right bundle branch block pattern on ECG (OR 4.7 95% CI 1.6–13.1). Hypotension, fever and malignancy were not significant. Both PERC and Wells criteria had poor positive predictive value (12% and 27% respectively), but the negative predictive value for PERC and Wells was 100% and 95.8% respectively. Inpatient CTPA appear to be over‐requested and can potentially be rationalised based on a combination of clinical predictors and Wells criteria and/or PERC rule. Further prospective studies are needed to develop accurate clinical decision tools targeted towards inpatients.
Publisher: American Society of Hematology
Date: 03-12-2015
DOI: 10.1182/BLOOD.V126.23.4678.4678
Abstract: Aim Thrombotic diseases are major causes of morbidity and mortality, and yet there are currently no laboratory tests to evaluate this risk. Global coagulation assays such as thrombin generation via calibrated automated thrombogram (CAT) and thromboelastography (TEG), may be better surrogate measures of an in idualÕs thrombosis risk. However, the evaluation of age, race and gender differences in the normal population is important prior to the inclusion of these assays into studies on diseased populations. Methods Normal controls with no thrombotic history and no anticoagulant/antiplatelet use were recruited. Routine tests were performed to exclude underlying risk factors including full blood count, thrombophilia screen and fasting lipids. All s les were citrated platelet poor plasma (PPP) s les were double-centrifuged at 2500G, aliquoted and frozen at -80o C within 2 hours of collection. TEG 5000S analysis was performed within 4 hours of collection, using whole citrated blood under standard manufacturer guidelines. CAT was performed with PPP using standard commercially available (STAGO) 5 pmol reagent and flurogenic (Fluca-Kit). Results 63 normal controls (43F, 20M) with median age of 36.5 (20-75) years were recruited. None had abnormal platelet or coagulation parameters. TEG: 36 volunteers (57%) had TEG parameters outside the manufacturerÕs normal range. Females and older in iduals (age years) had more prothrombotic TEG parameters including increased maximum litude (MA), alpha-angle and derived thrombin generation with reduced R and K time. Older females (age years) also had more prothrombotic parameters compared to younger females. Clot lysis (LY30) was significantly lower in the older population with no gender differences. (Table 1) CAT: Females had higher endogenous thrombin potential (ETP), which represented the total thrombin formed, and higher velocity index. Older in iduals had higher ETP but paradoxically a longer lag time. (Table 1) CAT vs TEG: There was no correlation between TEG parameters (such as MA or derived thrombin generation), and ETP via CAT (r2=0.005 and r2=0.006 respectively). Race differences: Of the 63 volunteers, 25 and 30 were of European and East Asian origin respectively. East Asians had significantly higher ETP, thrombin peak and velocity index (p .01), but these differences were less apparent using TEG, which also evaluated the platelet effect on clot formation. Statistically significant variation was only seen in the α-angle (p=0.04). (Table 2) Conclusion This study demonstrates that there are significant gender and age differences within the normal population. 57% of our volunteers had at least one TEG parameter outside the manufacturers reference range. Females had more prothrombotic parameters, which was independent of hormonal status. Older in iduals (age years) having more prothrombotic parameters, particularly clot lysis (LY30) using TEG, suggests a role of fibrinolysis in the futher evaluation of thrombotic risk. East Asians had significantly lower CAT parameters, which may explain the lower venous thrombotic risk seen in this population. Our results suggest that a localized reference range, tailored to gender, age and ethnicity is required for global coagulation assays. Table 1. Gender and age difference with TEG and CAT Male Female Age years Age ³50years No of controls 20 43 32 31 TEG parameters R time (min) 8.7 6.8 p .01 8.2 6.6 p =0.01 K time (min) 3.2 2.2 p .01 2.9 2.2 p =0.03 α-angle (¡) 50.6 59.8 p .01 52.2 61.3 p .01 MA (mm) 54.3 59.7 p .01 56.1 59.8 P=0.02 LY30 (%) 1.8 1.9 p=0.92 3.1 0.7 p .01 Derived Thrombin Gen 671 724 p .01 676 737 p .01 CAT parameters Lag Time (min) 3.0 3.2 p=0.53 2.8 3.4 p .01 ETP (nM/min) 1245 1399 p =0.03 1290 1403 p=0.06 Peak height (nM) 211 245 p=0.06 221 243 p=0.13 Vel Index (nM/min) 65 86 p =0.03 79 77 p=0.97 Time to Peak (min) 6.5 6.4 p=0.58 6.2 6.8 p=0.06 Table 2. Ethnic difference with CAT and TEG parameters Manufacturer values East Asian (n=30) European (n=25) p-value (% variation) TEG parameters R time (min) 2-8 7.8 6.8 0.15 (+14%) K time (min) 1-2 2.8 2.2 0.06 (+23%) α-angle (¡) 55-78 53.9 60.0 0.04 (-10%) MA (mm) 51-69 57.4 58.4 0.57 (-2%) Lysis time, LY30 (%) 0-8 1.9 2.4 0.53 (-34%) CAT parameters Not available Lag Time (min) 3.0 3.2 0.22 (-7%) ETP (nM/min) 1231.5 1411.7 .01 (-23%) Peak height (nM) 206.8 254.8 .01 (-19%) Vel Index (nM/min) 65.6 92.5 .01 (-30%) No relevant conflicts of interest to declare.
Publisher: Wiley
Date: 11-2020
DOI: 10.1111/IMJ.14640
Abstract: Clinical trials have demonstrated that direct oral anticoagulants (DOAC) are non-inferior to vitamin K antagonist for stroke prevention in non-valvular atrial fibrillation (AF) with comparable safety outcomes however, real-world Australian data are limited. To evaluate local real-world DOAC use focussing on safety, particularly in high-risk patients. A retrospective evaluation of 658 patients commenced or continued on DOAC between September 2013 and September 2016 for non-valvular AF at Northern Hospital, a tertiary hospital in Victoria, Australia was performed. Factor Xa inhibitors were more commonly prescribed than direct thrombin inhibitors (83.3 vs 16.7%) for AF management. The median patient age was 75 years. The rate of clinically significant bleeding on anticoagulation was 3.13 per 100 person-years (including four deaths) with risk factors including history of bleeding (hazard ratio (HR) 3.52, 95% confidence interval (CI) 1.22-10.17), concurrent antiplatelet therapy (HR 2.62, 95% CI: 1.11-6.20) and high falls risk (HR 2.76, 95% CI: 1.26-6.08). Patients on low-dose DOAC had significantly higher bleeding risk compared with those on full dose (5.05 vs 1.82 per 100 person-years). The rate of thrombotic stroke despite anticoagulation was 1.34 per 100 person-years with risk factors including low dose anticoagulation (P = 0.034), high falls risk (P = 0.046) and previous stroke (P = 0.028). DOAC use in real-world Australian practice is safe and effective, consistent with international data. Low dose anticoagulation and falls risk are associated with increased bleeding and thrombotic risk demonstrating overlapping risk factors. Careful in idualised patient risk assessment is still required as low dose anticoagulation is not without risks.
Publisher: Elsevier BV
Date: 11-2019
Publisher: MDPI AG
Date: 19-03-2016
DOI: 10.3390/DJ4010007
Publisher: Springer Science and Business Media LLC
Date: 08-01-2022
DOI: 10.1007/S11239-021-02621-1
Abstract: Thrombosis is one of the major global causes of morbidity and mortality, and predicting the risk of thrombotic and cardiovascular complications remains one of the key challenges in modern medicine. Conventional coagulation testing does not provide sufficient information, primarily because they measure the time to start of blood clotting and do not evaluate total thrombin generation. Possible adjunctive tools that may be helpful are global coagulation assays, which includes the assessment of the final products of the coagulation cascade, namely thrombin and fibrin. Whilst these assays have been more widely investigated in bleeding states, their role in thrombotic disorders is less established. We have previously investigated the use of assays such as thromboelastography, calibrated automated thrombogram and overall haemostatic potential assay in several hypercoagulable states including cardiovascular disease, haematological disorders and influence of hormone status as well as healthy controls. We provide a review of the use and limitations of global coagulation assays in healthy controls as well as hypercoagulable conditions.
Publisher: American Society of Hematology
Date: 29-11-2018
DOI: 10.1182/BLOOD-2018-99-112756
Abstract: Introduction: The introduction of direct oral anticoagulants (DOAC) has revolutionised the treatment of atrial fibrillation (AF) and venous thromboembolism (VTE). Previous clinical trials have demonstrated that DOACs are non-inferior to warfarin for treatment and prevention of VTE and at least as safe in terms of bleeding risk. However, there is limited data on real-world outcomes. We aim to evaluate the local real-world DOAC use with particular focus on safety and to specifically compare the safety outcomes of the warfarin era vs the DOAC era in the management of VTE. Method: Retrospective evaluation was performed with a total of 1696 patients reviewed including demographics and safety outcomes. Patients commenced or continuing on a DOAC for the treatment of AF and VTE at the Northern Hospital, a tertiary hospital in Victoria, Australia (September 2013 to September 2016, n=1079) were identified. A sub analysis was then performed comparing patients on DOAC for VTE indications to a separate retrospective local audit of VTE patients during the warfarin era (July 2011 to December 2012, n=617). For the purpose of the sub analysis, patients with active malignancy and thromboses other than deep vein thrombosis (DVT) and pulmonary embolus (PE) were excluded to maintain consistency with the warfarin era data. Results: A total of 1079 patients on DOAC with median age 70 years (range 17-96) were identified. The indications for DOAC were AF 61.4% (n=663), VTE treatment 30.5% (n=329) and VTE maintenance rophylaxis 8.1% (n=87). The most commonly prescribed DOAC was rivaroxaban 60.8% (n=656) followed by apixaban 28.7% (n=310) and dabigatran 10.5% (n=113). Of these patients 29.7% (n=320) were on low dose anticoagulation. Forty episodes of clinically significant bleeding (ISTH-SCC score 3-4) (3.7%) were captured [Table 1]. The average HASBLED score of these patients was 2 and significant risk factors for bleeding included low dose anticoagulation, AF patients, concurrent antiplatelet use, prior bleeding and high falls risk. In terms of thrombotic complications, there were 12 episodes of thrombotic stroke (1.8%) despite DOAC use with risk factors including low dose anticoagulation (p=0.03), prior stroke (p=0.04) and high falls risk (p=0.03). Nine patients on DOACs for VTE (2.2%) reported recurrence including a patient with active malignancy. 374 patients on DOAC for VTE management were included in the sub-analysis comparison to the warfarin audit (n=617). Of the DOAC patients, 88.2% (n=330) were on rivaroxaban and 11.8% (n=44) were on apixaban - 31.8% (n=315) were on DOAC for acute VTE treatment and 6.0% (n=59) for maintenance or prophylaxis at time of data collection. There were more unprovoked VTE in the DOAC group (66.0% (n=208) vs 42.0% (n=259), p .001). The patient demographics are outlined in Table 2. Overall, there were 28 clinically significant bleeding (ISTH-SCC score 3-4) events in the warfarin group (4.5%) and 8 in the DOAC group (2.1% p=0.05). The sites of bleeding were similar in both groups with gastrointestinal tract bleeding being the most common source. Forty-eight recurrent VTE events were captured - 39 occurred on warfarin (6.3%) and 9 while on DOAC (2.4% p=0.005). Conclusion: This retrospective audit shows that our local safety outcomes are comparable to clinical trials. Low dose anticoagulation and high falls risk (a surrogate marker of frailty) were significant risk factors for both clinically significant bleeding and thrombotic stroke in the DOAC population. These patients are likely frailer with greater co-morbidities and have shared risk factors for bleeding and stroke, suggesting that for these high risk patients, low dose anticoagulation does not negate their risk of complications and careful prescribing and close monitoring remain essential. The sub-comparison between VTE patients on DOAC and warfarin found that patients on warfarin had a higher rate of VTE recurrence in comparison to patients on DOAC. This may reflect patients maintaining more time on therapeutic anticoagulation with the more predictable DOACs compared to warfarin patients who may have more time below therapeutic range. There may also be a selection bias as-high risk patients with co-morbidities and those not meeting criteria for DOACs continue to be prescribed warfarin in the DOAC era. This data is similar to recent real-life DOAC experience in the atrial fibrillation population. Table 1. Table 1. No relevant conflicts of interest to declare.
Publisher: Wiley
Date: 27-10-2021
DOI: 10.1111/IJLH.13746
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.THROMRES.2016.04.003
Abstract: Isolated distal deep venous thrombosis (IDDVT) is traditionally associated with less severe clinical sequelae, with ongoing debate on multiple aspects of its management. Despite numerous studies evaluating its acute management, there remains a paucity of data evaluating long-term complications such as recurrence and subsequent malignancy. We aim to evaluate the characteristics of IDDVT in institutions that routinely perform whole leg ultrasonography, and the risks of recurrence and complications in comparison to major venous thromboembolism (major VTE defined as above-knee or proximal DVT and pulmonary embolism (PE)). Retrospective evaluation of consecutive IDDVT and major VTE from July 2011 to December 2012 in a hospital network in Melbourne, Australia. Patients were followed up for a minimum of 24months. Patients with active malignancy were excluded. Of 1024 VTE cases, there were 164 non-cancer patients (92 males, 72 females, median age of 61years) with IDDVT. Compared to major VTE, IDDVT was more likely to be provoked (73% vs 59%, p<0.01), has shorter duration of anticoagulation (median 3.5months vs 6.0months, p<0.01) and less clinically significant bleeding (2.4% vs 6.7%, p=0.05), independent of duration of therapy. Recurrence was non-inferior compared to major VTE (10% vs 7%, p=0.36) and 60% recurred with major VTE. Three (1.8%) were subsequently diagnosed with cancer (vs 1.9% in major VTE, p=0.97). IDDVT has non-inferior rates of recurrence and subsequent cancer detection compared to major VTE and hence, its clinical significance should not differ from major VTE. Further studies are required to determine the adequate length of anticoagulation.
Publisher: Wiley
Date: 10-11-2020
DOI: 10.1111/IJLH.13389
Publisher: Annex Publishers, LLC
Date: 04-2014
Publisher: Elsevier BV
Date: 06-2023
Publisher: Wiley
Date: 27-05-2022
DOI: 10.1111/IJLH.13881
Publisher: Oxford University Press (OUP)
Date: 11-2014
DOI: 10.1111/JTM.12152
Abstract: We report a case of a 51-year-old Han Chinese recently returned traveler, who was admitted with a generalized maculopapular rash, fevers, shock, and multi-organ failure. Extensive investigations failed to reveal an infective cause. Skin biopsy findings together with the recent commencement of allopurinol raised a diagnosis of drug reaction with eosinophilia and systemic symptom syndrome. High-dose prednisolone was commenced and the patient made a rapid recovery. This case highlights that not all sepsis-like presentations in returned travelers are due to infective causes and that severe drug reactions need to be considered in the differential diagnosis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-01-2022
Publisher: Informa UK Limited
Date: 03-2008
DOI: 10.1111/J.1444-0938.2007.00214.X
Abstract: Utilisation of low vision services remains low in Australia. This study investigates low vision service provision by optometrists in Victoria and assesses the optometric human resource potential. An eight-item questionnaire was sent to 1,050 optometrists in Victoria in December 2006. It investigated key characteristics of the optometrists and their practices, the extent of their low vision training and service provision and the influence of Medicare item 10942 on low vision service provision. Although only 97 replies were received they represented a significant proportion of optometrists who had undertaken postgraduate training in low vision. Almost 86 per cent of respondents worked in private practice settings. Although 87.6 per cent and 30.9 per cent had undergraduate and postgraduate low vision training, respectively, only 63.9 per cent of all respondents reported that they provided low vision services. The majority who replied to the impact of Medicare item 10942 question indicated that its introduction had not changed their low vision provision. Those who did not provide low vision services reported referrals to other low vision services as their main reason for not doing so. The majority of respondents represent a potential source of low vision service providers. Further work needs to explore their possible involvement in low vision care.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.THROMRES.2019.04.033
Abstract: Normal haemostasis requires maintenance of a careful equilibrium between the necessity to clot when bleeding and the retention of fluid phase at all other times. Disruption of this equilibrium can result in catastrophic outcomes, e.g. acute myocardial infarction and pulmonary embolism. However, despite the significant therapeutic advances in cardiovascular medicine over recent years, our ability to provide an accurate cardiovascular risk assessment remains an unmet need. Routine coagulation testing is not a useful reflection of haemostasis and cannot be reliably used to predict bleeding and thrombosis risks. Global coagulation assays such as viscoelastic testing, thrombin and fibrin generation have been proposed as better measures of the haemostatic function. These assays, particularly viscoelastic testing, have been increasingly used to assess bleeding risks and guide blood product replacement in trauma and massive transfusion settings. However, the role of these assays in thrombosis is less well-defined but given the complexities of the coagulation system, these global coagulation assays when used in combination may provide a better assessment of cardiovascular and thrombosis risk at an in idual level. Hence, we explore the role of some of the currently available global coagulation assays - the viscoelastic, thrombin generation and fibrin generation tests - and provide a review of the literature of the current evidence for these assays specifically in the field of venous thromboembolism and cardiovascular diseases.
Publisher: Springer Science and Business Media LLC
Date: 31-07-2022
DOI: 10.1007/S11239-022-02686-6
Abstract: Assessing the risk of recurrent venous thromboembolism (VTE), particularly when patients are anticoagulated, remains a major challenge largely due to the lack of biomarkers. Blood was s led from adult VTE patients recruited between January 2018 and September 2020, while receiving therapeutic anticoagulation. Results were compared to 144 healthy subjects (34.7% male, median age 42 years). Overall haemostatic potential (OHP) assay, a spectrophotometric assay, was performed on platelet-poor plasma, in which fibrin formation (triggered by small amounts of thrombin (overall coagulation potential, OCP)) and fibrinolysis (by the addition of thrombin and tissue plasminogen activator (OHP)) are simultaneously measured. Results were obtained from 196 patients (52.6% male, mean age 57.1 years). Compared to healthy subjects, VTE patients displayed significantly higher OCP (39.6 vs 34.5 units, p 0.001) and OHP (9.3 vs 6.4 units, p 0.001) as well as lower overall fibrinolytic potential (75.6 v s81.1%, p 0.001). All 16 VTE recurrences, including 11 unprovoked, occurred above an OCP cut-off of 40 th percentile (recurrence rate 4.32/100 patient-years (100PY), 95% confidence interval (CI) 2.39–7.80, p = 0.002). Of 97 patients who subsequently discontinued anticoagulation, all unprovoked VTE recurrences (n = 9) occurred above the 40 th OCP percentile (recurrence rate 9.10/100PY, 95% CI 4.74–17.49, p = 0.005) and the 40 th OHP percentile (recurrence rate 8.46/100PY, 95% CI 4.40–16.25, p = 0.009). Our pilot study demonstrates that the OHP assay can detect a hypercoagulable and hypofibrinolytic state in anticoagulated VTE patients and may be able to risk stratify VTE recurrence, allowing for more in idualised decision on long-term anticoagulation. Further larger prospective studies are required.
Publisher: Georg Thieme Verlag KG
Date: 20-03-2018
Abstract: The advent of direct oral anticoagulants (DOACs) has revolutionized anticoagulation management in both stroke prevention and venous thromboembolism (VTE) treatment revention. Clinical trials and secondary real-world data have shown that DOACs have similar efficacy and, in some cases, improved bleeding safety profiles compared with vitamin K antagonists. Together with benefits of patient convenience, this has shifted the risk–benefit ratio toward long-term anticoagulation. However, current VTE risk assessment models are based on vitamin K antagonists and do not take into account the new paradigm of DOACs. Therefore, challenges to the thrombosis community remain to determine patients who would benefit from long-term anticoagulation in the DOAC era. Here, the authors review the current literature on risks and benefits of DOACs and their potential role in long-term VTE thromboprophylaxis as well as in current risk assessment models. The increasing use of DOACs, led by their convenience of use and generally lower bleeding rates, calls for a reevaluation of the current models as the benefits of long-term anticoagulation may begin to outweigh risks and inconvenience associated with their predecessors.
Publisher: Wiley
Date: 26-10-2018
DOI: 10.1111/IJLH.12941
Abstract: Some patients with thrombocytopenia may be at risk of bleeding although quantitative platelet count is not always a sufficient predictive factor. Global coagulation assays such as thromboelastography (TEG Blood s les were collected from thrombocytopenic patients. TEG Fifty-eight participants (24 immune thrombocytopenia, 34 chemotherapy/malignancy-related) with mean age of 57.5 years were recruited. Compared to normal controls, thrombocytopenic participants had comparable maximum litude but reduced clot lysis (0.0% vs 0.6% P < 0.001) on TEG Global coagulation assays, particularly TEG
Publisher: American Society of Hematology
Date: 02-12-2016
DOI: 10.1182/BLOOD.V128.22.5708.5708
Abstract: Aim: To compare patients with newly diagnosed multiple myeloma (NDMM) withbortezomib responsive and resistant disease (defined as PR after 2 cycles) and assess the impact on clinical outcome particularly progression-free survival (PFS) and overall survival (OS). Method: Retrospective review of all patients identified with NDMM treated with upfront bortezomib in four tertiary centres in Victoria, Australia between 1st of January 2009 and 1st of March, 2016. Bortezomib responsiveness was defined as achievement of PR or better after completing 2 cycles of any bortezomib containing therapy (total eight doses of bortezomib). Prior radiotherapy was allowed. Data were analysed via log rank tests for PFS and OS using SAS (V9.4) software. Predictors of bortezomib resistance were assessed by chi-square analysis. Result: A total of 187 eligible patients were included (147bortezomib responsive and 40bortezomib resistant patients). Bortezomib resistance was associated with shorter median PFS, 27.4 (95%CI: 16.3, 30.8) vs 30.4 (95%CI: 23.4, 37.1) months (log-rank p= 0.047) with a median potential follow up of 27.4 vs 29.7 months in the resistant and responsive groups respectively. Estimated PFS at 12 months was 68.0% (95%CI: 50.3%, 80.5%) vs 88.3% (95%CI: 81.2%, 92.8%) and, at 24 months, 60.4% (95%CI: 41.7%, 74.7%) vs 60.0% (95%CI: 49.9%, 68.6%) in the resistant and responsive groups respectively, indicating non-constant hazard in the resistant group (see figure). Bortezomib resistance was not associated with higher ISS (ISS3 24% vs 15%, p=0.17), high riskcytogenetics (17p del ort(4 )) (23% vs 23%, p= 0.99), MM sub-type (p= 0.63) or length ofbortezomib cycle (21 vs 35 day p= 0.56)). In responders (n=147), maintenance therapy was associated with improved PFS (p=0.021), and PFS at 24 months was, 70.7% (95%CI: 57.3%, 80.5%) vs 46.9% (32.0%, 60.5%) in those who received maintenance therapy and those who did not respectively. In non-responders (n=40) PFS at 24 months was 68.8% (95%CI: 35.7%, 87.3%) vs 54.9% (31.6%, 73.2%) in those patients who received maintenance therapy and those patients who did not respectively (p=0.84). Median OS has not been reached in either thebortezomib resistant or responsive groups however estimated OS at 24 months is 82.8% (95%CI: 62.8%, 92.7%) vs 89.5% (95%CI: 81.5%, 94.1%) in the resistant and responsive groups respectively. Conclusion: Bortezomib resistance is a poor prognostic factor and is associated with a shorter PFS. Consideration of early therapy change, maintenance therapy and/or referral for assessment for allograft in eligible patients appears to be warranted. Figure Figure. No relevant conflicts of interest to declare.
Publisher: SAGE Publications
Date: 05-08-2021
DOI: 10.1177/1753495X211025397
Abstract: Risk assessment for venous thromboembolism in pregnancy and the puerperium is currently limited to stratifying clinical surrogate risk factors without high-quality evidence. While the absolute risk of pregnancy-associated venous thromboembolism is low for the vast majority of women, associated morbidity and mortality remains significant. As guidelines for thromboprophylaxis vary widely, some women may be under- or over-anticoagulated, contributing to poor outcomes. New global coagulation assays provide a holistic view of coagulation and may have the potential to detect hypercoagulability in pregnancy, unlike clinically available coagulation assays. However, there are major technical challenges to overcome before global coagulation assays can be realistically proposed as an adjunct to risk assessment for pregnancy-associated venous thromboembolism. This review summarises the literature and controversies in the prediction and prevention of pregnancy-associated venous thromboembolism and outlines the new tools in haematology that may assist in our future understanding of hypercoagulability in pregnancy.
Publisher: AME Publishing Company
Date: 2021
DOI: 10.21037/JLPM-20-95
Publisher: Wiley
Date: 23-05-2018
DOI: 10.1111/IJLH.12861
Abstract: Flow cytometry is used in the diagnosis of haematological diseases including chronic lymphoproliferative disorders. This audit aims to ascertain the real-world indications for peripheral blood (PB) flow cytometry and which of these are associated with higher diagnostic yields. All PB flow cytometry requests for chronic lymphoproliferative disorders from 1 January 2014 to 31 December 2014 were identified using the laboratory information system. Data including patient demographics, specialty of requestor, lymphocyte count and blood film report (if available), indications for tests and subsequent diagnosis were collected. A total of 185 requests with median patient age of 60 years were analysed. The main requestor was the Haematology Unit (n = 109 58.9%) although the diagnostic yield of their requests was not significantly better than other units combined (16.5% vs 13.2%, P = .49). Factors that significantly improved the diagnostic yield of testing were older age, the presence of atypical lymphocytes on the blood film and lymphocytosis (P < .01). Constitutional symptoms and cytopenias were not found to influence the diagnostic yield. PB flow cytometry is a useful tool when used in the appropriate clinical setting. Rationalisation of testing is important to reduce the futility of testing and unnecessary health costs.
Publisher: American Society of Hematology
Date: 06-12-2014
DOI: 10.1182/BLOOD.V124.21.4834.4834
Abstract: Aim Venous thromboembolism (VTE) is a major cause of morbidity and mortality and is estimated to cost approximately AUD$117 000 per person (Access Economics 2008). Despite advances in thrombosis management, recurrence rates remain high and management strategies are often heterogenous even within a single institution. While most studies have analysed specific aspects of VTE management, we aim to provide a holistic evaluation of real-world VTE management in the warfarin era including identifiying potential causal effects and complications. Method Retrospective evaluation of VTE over an 18-month period, from July 2011 to December 2012, at two major hospitals in Northeast Melbourne, Australia, including demographics, provoking factors, management, complications and mortality. Comparisons were made between cancer and non-cancer populations. Result 1003 patients, with median age of 63 (range 19-97) years, were identified including 26 recurrences (total 1029 episodes) - 577 (56%) pulmonary embolism (PE), 428 (42%) deep venous thrombosis (DVT). There was an overall male predominance (52%), particularly affecting the DVT subgroup (57% vs 48%, p=0.003) with no gender differences detected in the PE subgroup. 20% reported prior VTE and left limb DVT was more common (49% vs 43%, p=0.0008). The median follow up was 20 (range 10-32) months. NON-CANCER PATIENTS In this cohort, 63% had provoked VTE and thrombophilia screen was performed in 41%. The median duration of anticoagulation was 6 and 7 months for DVT and PE respectively. The majority (90%) was on warfarin for long-term anticoagulation. 5% required further interventions – IVC filter (n=28) and thrombolysis (n=15). 38% had end-of-treatment repeat imaging and residual clot was observed in 40%. Clot persistence was associated with increased recurrence risk, with an odds ratio of 2.64 (1.15 – 6.04, p=0.02). 8% had recurrent thrombosis with no difference between provoked versus unprovoked VTE (7.5% vs 9.0%, p=0.45). 5% reported grade III/IV bleeding, independent of duration of anticoagulation. Patients on enoxaparin had higher risk of bleeding (28% vs 10%, p .001). The all-cause mortality rate was 11%. In the sub-analysis of below knee DVT (BKDVT), 3 patients (1.5%) were subsequently diagnosed with cancer, similar prevalence to those with major VTE (1.7%), defined as proximal DVT and/or PE. BKDVT were more likely to be provoked (72% vs 55%, p .001) and recurrence was similar to major VTE (6.8% vs 8.7%, p=0.42) although patients with major VTE were more likely to experience grade III/IV bleeding complications (6.3% vs 1.0%, p=0.003) despite similar duration of therapy. Mortality rate in this cohort was 5.5% with no thrombosis-related deaths. CANCER PATIENTS 233 (23%) patients had active malignancy at time of VTE with 14 patients (1.4%) subsequently diagnosed. Cancer patients were older (67 vs 61 years, p .001) and had higher clot burden with more PE (64% vs 53%, p=0.004), proximal DVT (63% vs 46%, p=0.0008) and bilateral DVT (16% vs 5%, p .001) compared to non-cancer patients. Patients with metastatic cancer were also more likely to have unprovoked events (p=0.015). Cancer patients were more likely to require IVC filters (9% vs 3.6%, p .001) and lifelong anticoagulation (35% vs 18%, p .001). Recurrent thrombosis (16%, p .001) and Grade III/IV bleeding (9%, p=0.025) were more common. However, bleeding rates in cancer patients on long-term enoxaparin were similar to warfarin. Mortality rate in the cancer patients was 63% and were related to with higher incidence of complications-related deaths (p .001). Conclusion VTE is associated with significant mortality, even in non-cancer patients (11%). The annual recurrence rate is 6%, with malignancy and residual clot on repeat imaging being major risk factors. Cancer patients experience more Grade III/IV bleeding complications (9% vs 5%) and had higher clot burden and all-cause mortality compared to non-cancer patients. Interestingly, BKDVT, often considered a minor VTE, had comparable rates of recurrence and subsequent cancer detection to major VTE suggesting that the investigation and treatment of BKDVT should not differ from major VTE. Further evaluation of new treatment strategies as well as clinical and laboratory risk assessments are required to improve the management for VTE. This data will serve as an important baseline for future comparison in the new era of novel oral anticoagulants. No relevant conflicts of interest to declare.
Publisher: Springer Science and Business Media LLC
Date: 14-09-2022
DOI: 10.1007/S11739-022-03081-Y
Abstract: COVID-19 has rapidly evolved since it was first discovered in December 2019. We aimed to retrospectively review our experience with COVID-19 infection across 2020–2022, focusing on differences in laboratory markers at presentation. Consecutive adult patients admitted to hospital with confirmed COVID-19 infection were retrospectively reviewed across three periods (29/3/2020–29/9/2020, 16/8/2021–13/10/2021 and 1/1/2022–31/1/2022), correlating with the lineages B.1.338, Delta (B.1.617.2) and Omicron (B.1.1.159), respectively. Laboratory findings of the first requested blood test within 24 h of presentation were recorded and correlated with patient outcome. The primary outcome was requirement for oxygen therapy at any point. Inflammatory markers, namely serum ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP) were significantly lower on presentation during 2022 compared to 2021, corresponding to a milder disease course. More than 80% of 2022 patients had received 2 or more vaccine doses and fully vaccinated patients displayed significantly lower inflammatory markers at presentation. Using 2022 data, a multivariate prediction model was constructed to predict for oxygen requirement, with c -statistic 0.86. Patients in 2022, corresponding with the Omicron variant, displayed a milder disease course, even in hospitalised patients, with the majority not requiring oxygen and lower inflammatory markers. We constructed a simple-to-use risk prediction model with c -statistic 0.86 which may identify in iduals who can be safely managed as outpatients in the era of highly transmissible variants.
Publisher: Wiley
Date: 04-2022
DOI: 10.1111/IMJ.15631
Abstract: Early recognition of severe COVID‐19 is essential for timely patient triage. To report clinical and laboratory findings and patient outcomes at a tertiary hospital in Melbourne, Australia. This is a retrospective study of adult inpatients with COVID‐19 admitted to Northern Health from March to September 2020. Data were extracted from electronic medical records. Key admission data were available for 182 patients (median age 67.0 years (interquartile range, 47.9–83.1) 51.1% female). Fifty‐six (30.8%) were from residential care. One hundred and seventeen (64.3%) patients were assigned Goals of Patient Care (GOPC) A or B and 65 (35.7%) GOPC C or D. Comorbidities were present in 135 patients (74.2%). 63.2% of patients received antibiotics, 6.6% had antivirals, 45.6% received systemic glucocorticoid and 3.3% had tocilizumab. Fifty‐six (30.8%) developed clinical deterioration (24 requiring ventilation, 21 receiving critical care, 34 died). Overall, inhospital clinical deterioration was significantly associated with older age ( P 0.001), history of diabetes ( P = 0.038), lower lymphocyte count ( P = 0.002) and platelet count ( P = 0.004), higher neutrophil‐to‐lymphocyte ratio ( P = 0.002), elevated fibrinogen ( P = 0.004), higher serum ferritin ( P = 0.027) and C‐reactive protein (CRP P = 0.002). The accuracy of the 4C Deterioration model was moderate, with an area under the curve (AUC) of 0.79 (95% confidence interval (CI), 0.68–0.90) compared with an AUC of 0.77 (95% CI, 0.76–0.78) in the original validation cohort. In the present study, high neutrophil‐to‐lymphocyte ratio, abnormal d ‐dimer, high serum CRP and ferritin appear to be useful prognostic markers.
Publisher: Wiley
Date: 23-01-2023
DOI: 10.1111/IJLH.14020
Abstract: Activated charcoal based compounds such as DOAC‐stop™ (DS) have been developed to remove direct oral anticoagulant (DOAC) interference in‐vitro. However, few studies have used this approach with global coagulation assays (GCAs), such as thrombin generation assays, which are sensitive to the effect of DOACs. Thrombin generation with and without thrombomodulin (TM) via the automated ST‐Genesia system, and the overall haemostatic potential (OHP) assay, a spectrophotometric fibrin generation assay in which fibrin formation (triggered by small amounts of thrombin (overall coagulation potential, OCP)) and fibrinolysis (by the addition of thrombin and tissue plasminogen activator) were measured on (i) pooled normal plasma (PNP) spiked with varying amounts of rivaroxaban, apixaban, and dabigatran, and (ii) platelet poor plasma (PPP) from 21 non‐anticoagulated adults, before and after DS addition. Following the addition of DS to spiked PNP without thrombomodulin, thrombin and velocity index increased by 21.9% and 42.6%, respectively, while ETP increased by 6.93%. A decrease in OCP (−10.6%) and OHP (−12.7%) was observed following DS. Similar changes were seen post‐DS to plasma from non‐anticoagulated patients. Also in this group, pre‐ and post‐DS thrombin generation parameters showed high correlation, with the strongest observed for ETP ( R 2 = 0.94). There was a strong correlation for OHP parameters, with the closest seen with OCP ( R 2 = 0.96) and OHP ( R 2 = 0.95). DS causes some changes to the ETP and OHP assay, however, strong correlations were seen pre‐ and post‐DS in all GCA parameters. These findings support the use of DS to facilitate GCA testing in anticoagulated in iduals for evaluation of the underlying thrombotic state.
Publisher: Springer Science and Business Media LLC
Date: 27-05-2016
Publisher: Georg Thieme Verlag KG
Date: 02-09-2022
Abstract: Philadelphia chromosome-negative myeloproliferative neoplasms include polycythemia vera, essential thrombocythemia, and myelofibrosis. They are associated with increased thrombotic events, and the primary goal of therapy, in particular those with polycythemia vera and essential thrombocythemia, is the prevention of thrombotic complications typically with antiplatelet therapy and/or cytoreduction. While several patient-, disease-, and genomic-related factors have been identified to influence thrombotic risks, there are no routine laboratory investigations to date that are sufficiently accurate to assess the underlying procoagulant state and predict the thrombotic risks. Conventional coagulation testing only measures time to clot formation and cannot reliably predict bleeding and thrombotic risks. Global coagulation assays such as thromboelastography, thrombin, and fibrin generation may provide a more thorough assessment of hemostatic function. Thromboelastography and thromboelastometry are viscoelastic tests which measure the mechanical properties of the hemostatic process, including the global dynamics of clot formation, stabilization, and dissolution. While viscoelastic testing is gaining traction in the investigations of coagulopathies and goal-directed blood product replacement in trauma and massive transfusion settings, the role of these assays in thrombosis is less well defined. Here, we provide a review of the current evidence of the role of viscoelastic testing in myeloproliferative neoplasm, particularly in the thrombotic risk assessment.
Publisher: MDPI AG
Date: 14-12-2022
DOI: 10.3390/DIAGNOSTICS12123165
Abstract: Deep vein thrombosis (DVT) frequently leads to post-thrombotic syndrome (PTS) which is challenging to predict and prevent. Identifying those at high risk of developing PTS may help to focus preventative strategies. Adults were recruited within 3 months of DVT diagnosis. Blood was s led during the therapeutic anticoagulation phase. Overall hemostatic potential (OHP) assay, a spectrophotometric assay, was performed on platelet-poor plasma (PPP). In this assay, fibrin formation is triggered by small amounts of thrombin and termed the overall coagulation potential (OCP). Simultaneously, thrombin and tissue plasminogen activator are added to PPP and the resulting fibrin aggregation curve is the overall hemostatic potential (OHP). Fibrinolysis is expressed by the parameter overall fibrinolytic potential (OFP%). Patients were followed up at regular intervals. PTS was diagnosed if the Villalta score was ≥5 at least 3 months after the DVT diagnosis. Results were obtained from 190 patients (53.7% male, mean age 56.9 years). PTS developed in 62 (32.6%) patients. Patients with PTS displayed significantly higher median OCP (45.8 vs. 38.8 units, p = 0.010), OHP (12.8 vs. 9.2 units, p = 0.005) and significantly lower OFP (74.1 vs. 75.6%, p = 0.050). PTS patients had higher neutrophil/lymphocyte ratios (NLR) (2.3 vs. 1.9, p = 0.007). After multivariate analysis, proximal DVT location, history of varicose veins, NLR ≥ 2.6, OHP 13.0 units and weight kg were independent predictors for PTS. The c-statistic of the multivariate model was 0.77. This pilot study suggests that OHP testing while patients are still anticoagulated may assist in the prediction of PTS development and could assist in prognostication and targeting of preventative measures. However, larger prospective studies are needed to confirm these findings.
Publisher: Springer Science and Business Media LLC
Date: 13-02-2020
Publisher: Springer Science and Business Media LLC
Date: 16-04-2016
DOI: 10.1007/S11239-016-1362-3
Abstract: Cerebral venous thrombosis (CVT) is a rare venous thrombotic event. We review our local experience in the management of CVT in comparison to other venous thromboembolism (VTE) with specific focus on risk factors for thrombotic recurrence. Retrospective evaluation of consecutive CVT presentations from January 2005 to June 2015, at two major tertiary hospitals in Northeast Melbourne, Australia. This population was compared to a separate audit of 1003 consecutive patients with DVT and PE. Fifty-two patients (30 female, 22 male) with a median age of 40 (18-83) years, presented with 53 episodes of CVT. Twenty-nine episodes (55 %) were associated with an underlying risk factor, with hormonal risk factors in females being most common. The median duration of anticoagulation was 6 months with 11 receiving life-long anticoagulation. Eighty-one percent had residual thrombosis on repeat imaging, which was not associated with recurrence at the same or distant site. Nine (17 %) had CVT-related haemorrhagic transformation with two resultant CVT-related deaths (RR 22.5 p = 0.04). All three VTE recurrences occured in males with unprovoked events (RR 18.2 p = 0.05) who were subsequently diagnosed with myeloproliferative neoplasm (MPN). Compared to the non-cancer VTE population, non-cancer CVT patients were younger, had similar rate of provoked events and VTE recurrence, although with significantly higher rate of MPN diagnosis (RR 9.30 (2.29-37.76) p = 0.002) CVT is a rare thrombotic disorder. All recurrences in this audit occurred in male patients with unprovoked events and subsequent diagnosis of MPN, suggesting further evaluation for MPN may be warranted in patients with unprovoked CVT.
Publisher: Springer Science and Business Media LLC
Date: 31-08-2023
DOI: 10.1007/S12185-023-03651-6
Abstract: Post-thrombotic syndrome (PTS) is a common and potentially debilitating complication of deep vein thrombosis (DVT), affecting up to 50% of DVT patients. The consequence of this chronic condition includes reduced quality of life, increased use of the healthcare system and decreased productivity. The societal impact of this condition is projected to increase, given our ageing population and increased burden of thrombotic diseases. Despite significant recent advances in our understanding of PTS, many unanswered questions remain. Currently, there are few effective and proven options for established PTS hence, the emphasis should be on instituting effective prevention to reduce the progression to PTS. Effective anticoagulation lowers the risk of PTS, with direct oral anticoagulants appearing to outperform vitamin-K antagonists. However, the evidence for elastic compression stockings and endovascular thrombolysis or thrombectomy techniques remains unclear. Accurate identification of in iduals at high risk of developing PTS may also improve the targeting of preventative interventions. This review will examine the current body of evidence regarding PTS, with a focus on preventative strategies as well as novel biomarkers.
Publisher: American Society of Hematology
Date: 03-12-2015
DOI: 10.1182/BLOOD.V126.23.4468.4468
Abstract: Aim Cerebral venous thrombosis (CVT) accounts for 0.5-1.0% of all strokes and is a common cause of stroke in young people. The presentations are often heterogeneous and can be associated with significant morbidity and mortality. This review aims to evaluate our local experience in CVT compared to other venous thromboembolism (VTE) with a focus on risk factors for thrombotic recurrence. Methods Retrospective evaluation of consecutive CVT presentations from January 2005 to June 2015, at two major tertiary hospitals in Melbourne, Australia. Data collected included demographics, risk factors, management, complications, modified Rankin score (mRS) and mortality. Results 52 patients (31 female, 21 male) with median age 9.5 (18-83) years, including 4 with cancer, presented with 53 episodes of CVT. Females were younger (32 vs 41 years, p=0.06). Typical presenting symptoms were headache (87%), nausea/vomiting (43%), visual disturbances (38%), focal neurological deficits (28%) and seizures (17%). All but one case was symptomatic, with 53% reporting symptoms in the preceding week. 18 (34%) failed to be diagnosed on initial presentation while 35% (13/37) of CT brain yielded false negative for thrombosis all of which were subsequently diagnosed on magnetic resonance imaging (MRI) or CT angiography/venography. Commonly thrombosed sinuses included transverse/sigmoid (40%), superior sagittal (11%) or both (43%), with no location-dependent outcome differences. Nine (17%) had CVT-related haemorrhagic transformation and was associated with CVT-related death (2/9 vs 0/44 p=0.04). 28 episodes were provoked - twice more common in female (p=0.02) with 45% attributed to oral contraceptive pill(OCP). 44 patients (85%) had thrombophilia screen performed with 21% positivity. Median duration of anticoagulation was 6.5 months (8 remained on long-term) 78% treated with warfarin. Eight (15%) required intensive care support, while 2 patients required decompressive surgery. 12 (23%) were not followed up in our institutions. At last follow-up of the remaining 40, 2 (5%) had worsening mRS of ³ 2 compared to premorbid, 2 had CVT-related deaths and 2 succumbed to malignancy. 30% reported ongoing symptoms such as headaches, residual neurological deficits, seizures and memory impairment. There were three clot recurrences (1 CVT, 2 portal vein thrombosis) - all male with initial unprovoked events and were subsequently diagnosed with myeloproliferative neoplasm (MPN). Of the 3, one was positive for JAK2V617F mutation. Men with unprovoked CVT had a 20% risk of recurrence, significantly higher compared to women with unprovoked events (3/15 vs 0/10 p=0.02). Clot progression, defined as increased clot burden on repeat imaging, occurred in 2 patients - one was associated with MPN while another progressed in the setting of subtherapeutic anticoagulation post partum. There was one episode of Grade III bleeding (following a procedure) in addition to the 2 (4%) clot-related deaths discussed prior. Table 1.compares the characteristics of CVT and other VTE previously audited by us. Conclusions CVT is rare and may be missed on initial presentation (34%)_with a high degree of clinical suspicion required to improve detection rate. Given there was 35% of CT brain had false negative, MRI or CT angiography is the preferred modality of investigation. It is more common in young people, particularly females on OCP. The presence of haemorrhagic transformation was associated with higher mortality. All thrombotic recurrences in this audit occurred in men with unprovoked events, who were subsequently diagnosed with MPN. This suggests the need for further evaluation, particularly for MPN in males with unprovoked events. Table 1. Comparison between CVT and VTE patients CVT VTE RR p-value No of patients 52 743 No of episodes 53 753 Incidence 5 cases/year 502 cases/year Median age (years) 39 63 RR 0.39, p .001 Male genderRecurrence in males 21 (40%)3 (14%) 367 (49%)33 (9%) p=0.24 Provoked events 28 (53%) 467 (62%) p=0.23 Past VTE history 3 (6%) 157 (21%) RR 0.27, p=0.02 Positive family history 6 (12%) 56 (8%) p=0.29 Thrombophilia screen done (%)Any positive screen 44 (85%)11 (21%) 304 (40%)69 (23%) RR 2.10, p .001 p=0.76 Median duration of anticoagulation 6.5m Below knee VTE 3mMajor VTE 6m RecurrenceProvoked 3 (5%)0 (0%) 55 (7%)27 (6%) p=0.79p=0.39 Grade III/IV bleeding 3 (6%) 42 (6%) p=0.98 Non-cancer mortality 2 (4%) 109 (15%) RR 0.28, p=0.07 No relevant conflicts of interest to declare.
Publisher: MDPI AG
Date: 15-01-2021
Abstract: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality and is associated with high recurrence rates. The introduction of direct oral anticoagulants (DOACs) in the 2010s has changed the landscape of VTE management. DOACs have become the preferred anticoagulant therapy for their ease of use, predictable pharmacokinetics, and improved safety profile. Increasingly, guidelines have recommended long term anticoagulation for some indications such as following first unprovoked major VTE, although an objective in idualised risk assessment for VTE recurrence remains elusive. The balance of preventing VTE recurrence needs to be weighed against the not insignificant bleeding risk, which is cumulative with prolonged use. Hence, there is a need for an in idualised, targeted approach for assessing the risk of VTE recurrence, especially in those patients in whom the balance between benefit and risk of long-term anticoagulation is not clear. Clinical factors alone do not provide the level of discrimination required on an in idual level. Laboratory data from global coagulation assays and biomarkers may provide enhanced risk assessment ability and are an active area of research. A review of the prediction models and biomarkers for assessing VTE recurrence risk is provided, with an emphasis on contemporary developments in the era of DOACs and global coagulation assays.
No related grants have been discovered for Hui Yin Lim.