ABSTRACT
Background : Thromboprophylaxis is currently recommended for all COVID-19 patients requiring hospitalization. Whether therapeutic anticoagulation should be considered is highly debated. Aims : Compare mortality, thromboembolism, and bleeding rates between prophylactic and therapeutic anticoagulation. Methods : We performed a systematic search on PubMed and the Cochrane COVID-19 Study Register for studies comparing prophylactic and therapeutic anticoagulation, up to January 31, 2021. Search terms were: ('anticoagulant' OR 'anticoagulation' OR 'heparin' OR 'thromboprophylaxis') AND ('COVID-19' OR 'SARSCoV-2'). No language restriction was applied. Filters were applied to display comparative studies, clinical trials, and observational cohort studies. The Newcastle-Ottawa scale was used to assess the quality of included studies. Results : We identified 472 records and screened 412 for eligibility. Thirty-eight studies were found to be eligible, including thirty-four retrospective cohorts and four prospective studies. Twenty-three, twenty-two, and twenty-three studies were included in the metaanalysis of mortality, thromboembolism, and bleeding outcomes respectively. Patients receiving prophylactic anticoagulation had better survival compared to those treated with therapeutic anticoagulation (OR, 0.65, 95% CI, 0.46-0.91). Therapeutic anticoagulation did not decrease risk of thromboembolism and was associated with significantly higher risk of bleeding (Figures 1 and 2). Severe COVID-19 patients admitted to intensive care unit (ICU) showed a non-significant trend towards improved mortality (OR, 1.85, 95% CI 0.90-3.81), and lower rates of thromboembolism (OR, 1.46, 95% CI, 0.83-2.57) with therapeutic anticoagulation. Conclusions : To our knowledge, this is the first in-depth review of the outcomes of prophylactic versus therapeutic anticoagulation in COVID-19. Our findings argue against the empiric use of therapeutic anticoagulation in COVID-19 patients. Compared to prophylactic anticoagulation, therapeutic anticoagulation did not improve survival or reduce risk of thromboembolism, and was associated with significantly higher risk of bleeding. Prospective trials are encouraged to explore the benefit of therapeutic anticoagulation in critically ill COVID-19 patients admitted to ICU.