Anticoagulation in COVID-19: A Systematic Review, Meta-analysis, and Rapid Guidance From Mayo Clinic

Abstract

A higher risk of thrombosis has been described as a prominent feature of coronavirus disease 2019 (COVID-19). This systematic review synthesizes current data on thrombosis risk, prognostic implications, and anticoagulation effects in COVID-19. We included 37 studies from 4070 unique citations. Meta-analysis was performed when feasible. Coagulopathy and thrombotic events were frequent among patients with COVID-19 and further increased in those with more severe forms of the disease. We also present guidance on the prevention and management of thrombosis from a multidisciplinary panel of specialists from Mayo Clinic. The current certainty of evidence is generally very low and continues to evolve.

Figure 1

Analytic framework for the study. COVID-19 = coronavirus disease 2019.

Figure 2

Suggested approach to patients requiring hospitalization for coronavirus disease 2019 (COVID-19)–related complications. ^aActive bleeding, platelet count <30 × 10⁹/L, or congenital bleeding disorder including von Willebrand disease or hemophilia. ^bLaboratory tests: complete blood cell count and differential, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer. If PT and/or aPTT are prolonged, consider a special coagulation profile, which includes a lupus anticoagulant screen. Imaging: for patients presenting with a prolonged illness or those who have had a long hospital stay, consider obtaining bilateral lower extremity venous ultrasonography. ^cInitiate therapeutic anticoagulation therapy as follows: unfractionated heparin infusion is preferred; in a patient with a history of heparin-induced thrombocytopenia, use argatroban or bivalirudin (see direct thrombin inhibitors order set). ^dContinue oral anticoagulation for a minimum of 3 months with clinical reassessment thereafter. A direct oral anticoagulant (DOAC) is preferred unless the patient has another indication for the use of a vitamin K antagonist or low-molecular-weight heparin (LMWH). ^eAssess venous thromboembolism (VTE) risk using the D-dimer level as follows: low risk, <3.0 μg/mL; high risk, 3.0 μg/mL. This recommendation reflects a 6-fold increase above the upper limit of normal. Precise cutoff requires external validation. ^fOn day 7 of therapy (or earlier if clinical deterioration occurs), repeat the following studies: bilateral lower extremity venous ultrasonography; laboratory tests (complete blood cell count with differential, D-dimer, and fibrinogen). Consider alternating ultrasonography and laboratory tests every 3 to 4 days.