Antithrombotic Therapies in COVID-19 Disease: a Systematic Review
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Department of Medicine, Oregon Health & Science University, Portland, OR, USA; 2Department of Veterans Affairs Evidence Synthesis Program (ESP), VA Portland Healthcare System, Portland, OR, USA.
BACKGROUND: Infection with coronavirus SARS-CoV-2, causing COVID-19 disease, leads to inflammation and a prothrombotic state. OBJECTIVE: This rapid systematic review aims to synthesize evidence on thromboembolism incidence and outcomes with antithrombotic therapies in COVID-19. DATA SOURCES: We searched MEDLINE (Ovid), Cochrane Rapid Reviews, PROSPERO, and the WHO COVID-19 Database from January 1, 2003, to April 22, 2020, for studies meeting pre-specified inclusion criteria. STUDY SELECTION, DATA EXTRACTION, AND SYNTHESIS: One investigator identified articles for inclusion, abstracted data, and performed quality assessment, with second reviewer checking. RESULTS: Incidence of thromboembolism among hospitalized patients with COVID-19 ranged from 25 to 53% in 4 retrospective series. We identified 3 studies (1 retrospective cohort study, 1 prospective uncontrolled observational study, and 1 case series) examining outcomes among COVID-19 patients who received antithrombotic therapies. These studies all included different interventions (thromboprophylaxis with unfractionated heparin (UFH) or low molecular-weight heparin (LMWH); an intensive thromboprophylaxis protocol with LMWH, antithrombin, and clopidogrel; and salvage therapy with tissue plasminogen activator and heparin). These studies are overall poor quality due to methodological limitations including unclear patient selection protocols, lack of reporting or adjustment for patient baseline characteristics, inadequate duration of follow-up, and partial reporting of outcomes. CONCLUSIONS: New evidence on thromboembolism in COVID-19 does not warrant a change in current guidance on thromboprophylaxis among hospitalized patients. Prospective trials of antithrombotic treatment strategies among patients with COVID-19 are urgently needed. KEY WORDS: COVID-19; anticoagulants; thromboembolism; sepsis. J Gen Intern Med DOI: 10.1007/s11606-020-05906-y © Society of General Internal Medicine (This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply) 2020
Received April 29, 2020 Accepted May 4, 2020
INTRODUCTION
Infection with the novel coronavirus SARS-CoV-2, which causes the disease COVID-19, can lead to inflammation and a prothrombotic state characterized by elevations in D-dimer, fibrin/fibrinogen degradation products, and fibrinogen.1, 2 These lab abnormalities have been proposed as markers of severe disease and worse prognosis.1, 3 Although the cooccurrence of inflammation and hypercoagulability in sepsis has previously been recognized, including during the severe acute respiratory syndrome (SARS) epidemic of 2002–2003, clinicians and researchers studying COVID-19 are asking whether the risk of venous and arterial thromboembolism is higher in COVID-19 than with other sources of infection and whether COVID-19 patients
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