Pharmacologic Thromboprophylaxis and Thrombosis in Hospitalized Patients with COVID-19: A Pooled Analysis

Abstract

Background: Coronavirus disease 2019 (COVID-19) increases thrombosis in hospitalized patients prompting adoption of different thromboprophylaxis strategies. Safety and efficacy of escalated-dose pharmacologic thromboprophylaxis are not established.

Objectives: To determine the pooled incidence of thrombosis/bleeding in hospitalized patients with COVID-19 for standard-dose, intermediate-dose, therapeutic anticoagulation, and no pharmacologic thromboprophylaxis.

Methods: MEDLINE, EMBASE, and Cochrane CENTRAL were searched up to August 29, 2020 for studies reporting pharmacologic thromboprophylaxis and thrombosis or bleeding. Pooled event rates were calculated using a random-effects model.

Results: Thirty-five observational studies were included. The pooled incidence rates of total venous thromboembolism (N = 4,685) were: no prophylaxis 41.9% (95% confidence interval [CI]: 28.1-57.2, I ² = 76%), standard-dose prophylaxis 19.8% (95% CI: 13.2-28.6, I ² = 95%), intermediate-dose prophylaxis 11.9% (95% CI: 4.3-28.6, I ² = 91%), and therapeutic-dose anticoagulants 10.5% (95% CI: 4.2-23.8, I ² = 82%, p = 0.003). The pooled incidence rates of arterial thrombosis (N = 1,464) were: no prophylaxis 11.3% (95% CI: 5.2-23.0, I ² = 0%), standard-dose prophylaxis 2.5% (95% CI: 1.4-4.3, I ² = 45%), intermediate-dose prophylaxis 2.1% (95% CI: 0.5-7.7, I ² = 45%), and therapeutic-dose anticoagulants 1.3% (95% CI: 0.2-8.8, I ² = 0, p = 0.009). The pooled bleeding event rates (N = 6,393) were nonsignificantly higher in therapeutic-dose anticoagulants compared with standard-dose prophylaxis, (6.3 vs. 1.7%, p = 0.083).

Conclusion: Thrombosis rates were lower in hospitalized COVID-19 patients who received pharmacologic thromboprophylaxis. Thrombosis and bleeding rates for patients receiving intermediate-dose thromboprophylaxis or therapeutic anticoagulation were similar to those who received standard-dose pharmacologic thromboprophylaxis.

Fig. 1

PRISMA diagram.

Fig. 2

Forest plot showing the pooled incidence of total venous thromboembolism amongst pharmacologic thromboprophylaxis strategies: no prophylaxis, standard prophylaxis, intermediate prophylaxis, and full-dose therapeutic anticoagulation. Total VTE included symptomatic or asymptomatic VTE (lower and upper extremity DVT, PE, and catheter-associated thrombosis). DVT, deep vein thrombosis; PE, pulmonary embolism; VTE, venous thromboembolism.