Heparin formulation and thromboprophylaxis intensity in critically ill patients: Results from the ESICM UNITE...

Decisions regarding heparin formulation and thromboprophylaxis intensity are central to intensive care practice, yet the optimal strategy remains uncertain. We evaluated associations between anticoagulation strategies and three primary outcomes - life-threatening haemorrhage, thromboembolic events, and transfusion requirement - in a large international critically ill COVID-19 cohort.

Two analyses used variables pre-specified in the ESICM UNITE-COVID registry. First, outcomes were compared between unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) among patients receiving therapeutic anticoagulation for confirmed thromboembolism or with prophylactic intent. Second, outcomes were compared between standard and therapeutic-equivalent LMWH thromboprophylaxis with prophylactic intent.

Among 3062 patients receiving therapeutic anticoagulation (811 UFH, 2251 LMWH), UFH was associated with higher rates of life-threatening haemorrhage (16.7% vs 7.7%; risk difference 9.0% [95% CI 5.8-12.3%]) and greater transfusion requirements (mean 4.2 vs 1.4 units; mean difference 2.79 [95% CI 2.11-3.47]). Among 1709 patients receiving therapeutic dose-equivalent anticoagulation with prophylactic intent, UFH was associated with more thromboembolic events (16.1% vs 9.7%; RD 6.4% [95% CI 1.5-11.3%]). Among 3555 patients receiving LMWH thromboprophylaxis, therapeutic-equivalent dosing was associated with fewer thromboembolic events (16.4% vs 22.0%; RD -5.6% [95% CI -9.2 to -1.7%]) without increased life-threatening haemorrhage (4.6% vs 5.8%; RD -1.2% [95% CI -3.5 to 1.1%]).

During therapeutic anticoagulation, LMWH was associated with a more favourable observed safety profile than UFH, with lower rates of haemorrhage and transfusion requirements, and fewer thromboembolic events among patients treated with prophylactic intent. Higher-intensity LMWH thromboprophylaxis was associated with fewer thromboembolic events without increased haemorrhage; however, ICU mortality was higher in the therapeutic-equivalent group, a finding that may reflect residual confounding but warrants caution. These hypothesis-generating findings should be interpreted in the context of existing randomised trial evidence and evaluated prospectively.