Comparison of Unfractionated Heparin and Low‐Molecular‐Weight Heparin in Acute Cerebral Venous Thrombosis: A Subanalysis of the CLOT‐VENUS Registry

BACKGROUND: Optimal anticoagulation in acute cerebral vein thrombosis remains uncertain. We compared unfractionated heparin (UFH) and enoxaparin, and identified predictors of functional recovery and UFH responsiveness. METHODS: This retrospective 2-center study from the multicenter international CLOT-VENUS (Collaboration on Cerebral Venous Thrombosis) registry included adults with acute cerebral vein thrombosis treated with UFH or enoxaparin (2004-2024). Baseline clinical, laboratory, and imaging data were collected. UFH response was measured via a composite responsiveness index (Unfractionated Heparin Composite Response Index) based on partial thromboplastin time. The primary outcome was 6-month functional status (modified Rankin Scale [mRS]), and secondary outcomes included discharge mRS and death. RESULTS: Among 359 patients (median age, 40 [interquartile range, 28-54] years; 68.5% women), 220 (61.3%) received UFH and 139 (38.7%) enoxaparin. Only 64% of partial thromboplastin time values fell within the therapeutic range. UFH was associated with worse outcomes at discharge (mRS score, 3-6: adjusted odds ratio, 2.89; mRS score, 2-6: adjusted odds ratio, 1.90; ordinal mRS score, adjusted odds ratio, 1.56) and at 6 months (mRS score, 3-6: adjusted odds ratio, 2.63). Poor recovery was independently linked to the UFH composite responsiveness index and frequent infusion adjustments. Notably, in the sensitivity analysis limited to patients on UFH with ≥50%, ≥67%, and ≥79% therapeutic partial thromboplastin time values, the outcome differences diminished. Age was independently associated with UFH responsiveness, and female sex, body mass index, and NLR with the number of UFH infusion-rate adjustments. CONCLUSIONS: Treatment with UFH was associated with worse clinical outcomes compared with enoxaparin, largely attributable to suboptimal and inconsistent anticoagulation. However, when UFH achieves consistent therapeutic levels, the outcomes are comparable. Early predictors may help guide individualized anticoagulation strategies.