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

PURPOSE: 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.

METHODS: 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.

RESULTS: 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%]).

CONCLUSIONS: 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.