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BACKGROUND: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. METHODS: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. FINDINGS: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). INTERPRETATION: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population. ispartof: THROMBOSIS RESEARCH vol:222 pages:31-39 ispartof: location:United States status: published

Background: COVID-19 is associated with inflammation and an increased risk of thromboembolic complications. Prophylactic doses of low-molecular-weight heparin have been used in hospitalised and non-critically ill patients with COVID-19. We aimed to evaluate the efficacy and safety of prophylactic low-molecular-weight heparin (enoxaparin) versus standard of care (no enoxaparin) in at-risk outpatients with COVID-19. Methods: This open-label, multicentre, randomised, controlled, phase 3b trial (ETHIC) was done at 15 centres in six countries (Belgium, Brazil, India, South Africa, Spain, and the UK). We consecutively enrolled participants aged at least 30 years who had not received a COVID-19 vaccine and had symptomatic, confirmed COVID-19 in the outpatient setting plus at least one risk factor for severe disease. Within 9 days of symptom onset and by use of a web-based random block design (block size either 2 or 4), eligible participants were randomly assigned (1:1) to receive either subcutaneous enoxaparin for 21 days (40 mg once daily if they weighed Findings: Following the advice of the Data and Safety Monitoring Board, this study was terminated early due to slow enrolment and a lower-than-expected event rate. Between Oct 27, 2020, and Nov 8, 2021, 230 patients with COVID-19 were assessed for eligibility, of whom 219 were enrolled and randomly assigned to receive standard of care (n=114) or enoxaparin (n=105). 96 (44%) patients were women, 122 (56%) were men, and one patient had missing sex data. 141 (65%) of 218 participants with data on race and ethnicity were White, 60 (28%) were Asian, and 16 (7%) were Black, mixed race, or Arab or Middle Eastern. Median follow-up in both groups was 21 days (IQR 21–21). There was no difference in the composite of all-cause mortality and hospitalisation at 21 days between the enoxaparin group (12 [11%] of 105 patients) and the standard-of-care group (12 [11%] of 114 patients; unadjusted hazard ratio 1·09 [95% CI 0·49–2·43]; log-rank p=0·83). At 21 days, two (2%) of 105 patients in the enoxaparin group (one minor bleed and one bleed of unknown severity) and one (1%) of 114 patients in the standard-of-care group (major abnormal uterine bleeding) had a bleeding event. 22 (21%) patients in the enoxaparin group and 13 (11%) patients in the standard-of-care group had adverse events. The most common adverse event in both groups was COVID-19-related pneumonia (six [6%] patients in the enoxaparin group and five [4%] patients in the standard-of-care group). One patient in the enoxaparin group died and their cause of death was unknown. Interpretation: The ETHIC trial results suggest that prophylaxis with low-molecular-weight heparin had no benefit for at-risk outpatients with COVID-19. Although the trial was terminated early, our data, combined with data from similar studies, provide further insights to inform international guidelines and influence clinical practice.

Severe coronavirus disease 2019 (COVID-19) is characterized by marked hypoxaemia and lung oedema, often accompanied by disordered blood coagulation and fibrinolytic systems, endothelial damage and intravascular fibrin deposition.We present a retrospective observational study of 104 patients admitted to hospital with COVID-19. Plasma samples were collected within 72 h of admission. In addition to routine coagulation and haematology testing, soluble thrombomodulin (sTM), thrombin-antithrombin (TAT), tissue plasminogen activator-plasminogen activator inhibitor 1 complex (tPAI-C) and plasmin-α2 antiplasmin complex (PIC) were performed by automated chemiluminescent enzyme immunoassays.Significantly higher levels of D-dimer, TAT, sTM and tPAI-C were observed in non-survivors compared to survivors. To confirm which parameters were independent risk factors for mortality, multiple logistic regression was performed on D-dimer, TAT. sTM, tPAI-C and PIC data. Only increasing sTM was significantly associated with mortality, with an odds ratio of 1.065 for each 1.0 TU/mL increment (95% CI 1.025-1.115).Of the haemostatic variables measured, sTM, which can be rapidly assayed, is the best independent predictor of mortality in patients hospitalized with COVID-19, and this suggests that endothelial dysfunction plays an important role in disease progression.

Background: There is limited information on the influence of body mass index (BMI) on clinical outcomes in patients with venous thromboembolism (VTE). Objectives: Investigate the influence of BMI on baseline characteristics, treatment patterns, and 24-month outcomes in VTE patients. Methods: GARFIELD-VTE is a prospective, non-interventional study of 10869 patients with objectively confirmed VTE. Patients were grouped according to BMI

ELIXIR EOSC Strategy poster 2022.

Document detailing ELIXIR Europe's strategy for engagement with the European Open Science Cloud (EOSC)as produced by the ELIXIR-EOSC Focus Group, 2022.

Therapeutic plasma exchange (TPE) is used for several chronic conditions with little evidence on the efficacy and safety of different choice of replacement fluid. Measurement of haemostasis, particularly in vitro thrombin generation, could play a role in determining the immediate efficacy of different fluid replacement.To determine the impact of different TPE replacement fluid regimens on haemostatic assays.Prospective observational multi-centre cohort study in adult patients 18 years and older evaluating haemostatic changes between four different TPE regimens: (1) 5% human albumin solution (Alb) only, (2) 50:50 mix of 5% Alb + modified gelatin, (3) 70:30 mix of 5% Alb and normal saline (NS), and (4) solvent-detergent, virus-inactivated fresh frozen plasma (FFP) (either alone or combined with other fluids). Twenty-one haemostasis variables were analysed (procoagulant, anticoagulant and fibrinolytic factors) pre and post TPE sessions, including in vitro thrombin generation. Linear mixed modelling and canonical discriminant analyses were used to examine the effect of TPE fluid type on haemostatic variables.A total of 31 patients with up to 5 TPE sessions each (131 sessions in total) were enrolled. Out of 21 markers analysed using linear mixed modelling, the main effects of fluid type were found to be significant for 19 markers (P 0.05), excluding plasminogen activator inhibitor-1 antigen and thrombin-anti-thrombin. Multivariate Analysis of Variance showed significant differences between the fluid types (Wilks' lambda = 0.07; FThrombin generation and fibrinogen discriminated better the effect of different TPE fluids on haemostasis and should be considered as potential markers to evaluate the immediate haemostatic effect of TPE procedures. The use of NS as a TPE replacement fluid had a distinctive impact on thrombin generation and fibrinogen responses compared to other non-FFP fluids.

Objective The aim of this systematic scoping review is to identify and categorize the outcome measures that have been reported in clinical studies, where therapeutic plasma exchange (TPE) has been used as an intervention in any clinical settings, excluding thrombotic thrombocytopenic purpura (TTP). Methods We searched electronic databases using a predefined search strategy from inception to October 9, 2020. Two reviewers independently screened and extracted data. Results We included 42 studies (37 RCTs and 5 prospective cohort studies) grouped into six main categories (neurology, immunology, renal, rheumatology, hematology, and dermatology). Primary outcomes were defined in eight studies (19%, 8/42) and were categorized as efficacy (five studies) or patient reported outcomes (three studies). A power calculation was reported in six studies (75%, 6/8): five neurology studies (mainly patient reported outcomes) and a single immunological study (efficacy outcome). Disease-specific efficacy outcomes were dependent on the clinical setting of the population receiving TPE. Most of the trials (43%, 18/42) were undertaken in patients with neurology conditions where clear, disease-specific, clinical outcome measures were used, including neurological disability scales (11/18, 61%), change in neurological examination (9/18, 50%), and functional improvement scores (7/18, 39%). For other conditions, the reporting of disease-specific outcomes was poorly reported. Safety outcomes were mainly related to replacement fluid type rather than being disease-specific. The most common outcome reported was hypotension (19%, 8/42), and this was primarily in patients exchanged with albumin. Conclusion Future clinical studies to determine which fluid replacement option is most efficacious and safe should use disease-specific outcomes, as a trial in one therapeutic area may not necessarily translate to another therapeutic area. Patient reported outcomes are not universally reported for all disease areas. Safety measures focused primarily on fluid safety.