Optimal dosing of heparin for prophylactic anticoagulation in critically ill COVID-19 patients a systematic review and meta-analysis of randomized controlled trials

Abstract

Purpose: The optimal amount of anticoagulation for critically ill COVID-19 patients is controversial. Therefore, we aimed to evaluate the efficacy and safety of escalated doses of anticoagulation in critically ill patients with severe COVID-19.

Materials and methods: We conducted a systematic search of three major databases, including PubMed, Cochrane Library, and Embase, from inception to May 2022. Randomized controlled trials (RCTs) were included comparing therapeutic or intermediate doses to standard prophylactic doses of anticoagulants in critically ill COVID-19 patients, with heparins as the only anticoagulation therapy considered.

Results: Out of the six RCTs, 2130 patients were administered escalated dose anticoagulation (50.2%) and standard thromboprophylaxis therapy (49.8%). The escalated dose showed no significant impact on mortality (RR, 1.01; 95% CI, 0.90-1.13). Although there was no significant difference in DVT (RR, 0.81; 95% CI, 0.61-1.08), the risk of PE was significantly reduced in patients receiving escalated dose anticoagulation (RR, 0.35; 95% CI, 0.21-0.60), with an increased risk of bleeding events (RR, 1.65; 95% CI, 1.08-2.53).

Conclusion: This systematic review and meta-analysis fail to support escalated anticoagulation doses to reduce mortality in critically ill COVID-19 patients. However, higher doses of anticoagulants appear to reduce thrombotic events while increasing the risk of bleeding effectively.

Keywords: Anticoagulants; Bleeding; COVID-19; Critical care; Heparin; Hypercoagulability; Intensive care unit; Mortality; SARS-CoV2; Safety; Venous thromboembolism; meta-analysis.