Preventing Thrombotic Complications in Severe COVID-19: Full-Dose or Standard-Dose Anticoagulation?

COVID-19 carries excess risk for venous and arterial thrombotic complications driven by a hyperactive platelet-neutrophil interaction, endothelial cell dysfunction, and activation of the coagulation cascade. Despite the known benefits of anticoagulation in critically ill patients with COVID-19, optimal dosing remains uncertain. In the COVID-PACT study (an open-label trial in patients with COVID-19 receiving intensive care unit [ICU] care), Bohula and colleagues randomized 390 patients at 34 U.S. centers to full-dose anticoagulation or prophylactic doses of anticoagulation therapy; 292 patients with no contraindications to antiplatelet therapy were additionally randomized to clopidogrel or no clopidogrel.

At randomization, 99% of patients were on advanced respiratory therapy, including 15% on mechanical ventilation; 40% required invasive mechanical ventilation at some point during hospitalization. Full-dose anticoagulation substantially reduced venous or arterial thrombotic events compared with prophylactic anticoagulation (9.9% vs. 15.2%). No additional benefit was conferred by clopidogrel. Fatal or life-threatening bleeding occurred in four patients in the full-dose anticoagulated group versus one in the prophylactic-dose group (2.1% vs. 0.5%), but all-cause mortality did not differ between groups.