BACKGROUND: Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated by a significant coagulopathy, that likely manifests in the form of both microthrombosis and VTE. This recognition has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE.METHODS: A group of approved panelists developed key clinical questions by using the PICO (Population, Intervention, Comparator, Outcome) format that addressed urgent clinical questions regarding the prevention, diagnosis, and treatment of VTE in patients with COVID-19. MEDLINE (via PubMed or Ovid), Embase, and Cochrane Controlled Register of Trials were systematically searched for relevant literature, and references were screened for inclusion. Validated evaluation tools were used to grade the level of evidence to support each recommendation. When evidence did not exist, guidance was developed based on consensus using the modified Delphi process. RESULTS:The systematic review and critical analysis of the literature based on 13 Population, Intervention, Comparator, Outcome questions resulted in 22 statements. Very little evidence exists in the COVID-19 population. The panel thus used expert consensus and existing evidence-based guidelines to craft the guidance statements. CONCLUSIONS:The evidence on the optimal strategies to prevent, diagnose, and treat VTE in patients with COVID-19 is sparse but rapidly evolving.

Background Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. Methods In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care–level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d -dimer level. Results The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support–free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d -dimer cohort, 92.9% in the low d -dimer cohort, and 97.3% in the unknown d -dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. Conclusions In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589 , NCT04505774 , NCT04359277 , and NCT02735707 .)