Randomized trials of therapeutic heparin for COVID-19: A meta-analysis.

BACKGROUND: Pulmonary endothelial injury and microcirculatory thromboses likely contribute to hypoxemic respiratory failure, the most common cause of death, in patients with COVID-19. Randomized controlled trials (RCTs) suggest differences in the effect of therapeutic heparin between moderately and severely ill patients with COVID-19. We did a systematic review and meta-analysis of RCTs to determine the effects of therapeutic heparin in hospitalized patients with COVID-19. METHODS: We searched PubMed, Embase, Web of Science, medRxiv, and medical conference proceedings for RCTs comparing therapeutic heparin with usual care, excluding trials that used oral anticoagulation or intermediate doses of heparin in the experimental arm. Mantel-Haenszel fixed-effect meta-analysis was used to combine odds ratios (ORs). RESULTS AND CONCLUSIONS: There were 3 RCTs that compared therapeutic heparin to lower doses of heparin in 2854 moderately ill ward patients, and 3 RCTs in 1191 severely ill patients receiving critical care. In moderately ill patients, there was a nonsignificant reduction in all-cause death (OR, 0.76; 95% CI, 0.57-1.02), but significant reductions in the composite of death or invasive mechanical ventilation (OR, 0.77; 95% CI, 0.60 0.98), and death or any thrombotic event (OR, 0.58; 95% CI, 0.45-0.77). Organ support-free days alive (OR, 1.29; 95% CI, 1.07-1.57) were significantly increased with therapeutic heparin. There was a nonsignificant increase in major bleeding. In severely ill patients, there was no evidence for benefit of therapeutic heparin, with significant treatment-by-subgroup interactions with illness severity for all-cause death (P = .034). In conclusion, therapeutic heparin is beneficial in moderately ill patients but not in severely ill patients hospitalized with COVID-19.

Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress.

The 2020 Congress of the International Society of Thrombosis and Haemostasis (ISTH) was held virtually July 12-15, 2019, due to the coronavirus disease 2019 pandemic. The congress convenes annually to discuss clinical and basic topics in hemostasis and thrombosis. Each year, the program includes State of Art (SOA) lectures given by prominent scientists. Presenters are asked to create Illustrated Capsules of their talks, which are concise illustrations with minimal explanatory text. Capsules cover major themes of the presentation, and these undergo formal peer review for inclusion in this article. Owing to the shift to a virtual congress this year, organizers reduced the program size. There were 39 SOA lectures virtually presented, and 29 capsules (9 from talks omitted from the virtual congress) were both submitted and successful in peer review, and are included in this article. Topics include the roles of the hemostatic system in inflammation, infection, immunity, and cancer, platelet function and signaling, platelet function disorders, megakaryocyte biology, hemophilia including gene therapy, phenotype tests in hemostasis, von Willebrand factor, anticoagulant factor V, computational driven discovery, endothelium, clinical and basic aspects of thrombotic microangiopathies, fibrinolysis and thrombolysis, antithrombotics in pediatrics, direct oral anticoagulant management, and thrombosis and hemostasis in pregnancy. Capsule authors invite virtual congress attendees to refer to these capsules during the live presentations and participate on Twitter in discussion. Research and Practice in Haemostasis and Thrombosis will release 2 tweets from @RPTHJournal during each presentation, using #IllustratedReview, #CoagCapsule and #ISTH2020. Readers are also welcome to utilize capsules for teaching and ongoing education.

Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial.

OBJECTIVE: To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards. DESIGN: Randomised controlled, adaptive, open label clinical trial. SETTING: 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US. PARTICIPANTS: 465 adults admitted to hospital wards with covid-19 and increased D-dimer levels were recruited between 29 May 2020 and 12 April 2021 and were randomly assigned to therapeutic dose heparin (n=228) or prophylactic dose heparin (n=237). INTERVENTIONS: Therapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death. MAIN OUTCOME MEASURES: The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care unit, assessed up to 28 days. The secondary outcomes included all cause death, the composite of all cause death or any mechanical ventilation, and venous thromboembolism. Safety outcomes included major bleeding. Outcomes were blindly adjudicated. RESULTS: The mean age of participants was 60 years; 264 (56.8%) were men and the mean body mass index was 30.3 kg/m2. At 28 days, the primary composite outcome had occurred in 37/228 patients (16.2%) assigned to therapeutic heparin and 52/237 (21.9%) assigned to prophylactic heparin (odds ratio 0.69, 95% confidence interval 0.43 to 1.10; P=0.12). Deaths occurred in four patients (1.8%) assigned to therapeutic heparin and 18 patients (7.6%) assigned to prophylactic heparin (0.22, 0.07 to 0.65; P=0.006). The composite of all cause death or any mechanical ventilation occurred in 23 patients (10.1%) assigned to therapeutic heparin and 38 (16.0%) assigned to prophylactic heparin (0.59, 0.34 to 1.02; P=0.06). Venous thromboembolism occurred in two patients (0.9%) assigned to therapeutic heparin and six (2.5%) assigned to prophylactic heparin (0.34, 0.07 to 1.71; P=0.19). Major bleeding occurred in two patients (0.9%) assigned to therapeutic heparin and four (1.7%) assigned to prophylactic heparin (0.52, 0.09 to 2.85; P=0.69). CONCLUSIONS: In moderately ill patients with covid-19 and increased D-dimer levels admitted to hospital wards, therapeutic heparin was not significantly associated with a reduction in the primary outcome but the odds of death at 28 days was decreased. The risk of major bleeding appeared low in this trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04362085.