Comparison of Unfractionated Heparin and Low Molecular Weight Heparin in Acute Cerebral Venous Thrombosis: A Sub-analysis of the CLOT-VENUS Registry
Milagros Galecio-Castillo1, Leonardo Cruz1, Amir Shaban2, Vanessa Cano-Nigenda3, Aaron Rodriguez-Calienes4, Brian Smith2, James Torner2, Nicholas Mohr1, Andres Mercado-Pompa3, Nashwa Abdelhakim5, Anderson Brito-Alvarado1, Andres Pereda-Castillo3, Antonio Arauz6, Santiago Ortega Gutierrez2
1University of Iowa Health Care, 2University of Iowa, 3Instituto Nacional de Neurologia y Neurocirugia, 4University of Iowa Hospitals and Clinics, 5Minia Faculty of Medicine, 6Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
Objective:
To compare unfractionated heparin (UFH) and enoxaparin, and identified predictors of functional recovery and UFH responsiveness in patients in acute cerebral vein thrombosis (CVT).
Background:
Anticoagulation therapy, primarily with intravenous IV-UFH infusion or subcutaneous low-molecular-weight heparin (LMWH), remains the cornerstone of acute CVT. Although LMWH is generally preferred due to a more favorable profile, UFH continues to be widely used, particularly in critically ill patients and in acute hospital settings where rapid reversal may be required for emergent surgical interventions.
Design/Methods:
This cross-sectional study included adults with acute CVT treated with UFH or enoxaparin (2004–2024). UFH response was measured via a composite responsiveness index (UFH-CRI) based on partial thromboplastin time (PTT). The primary outcome was 6-month mRS. Secondary outcomes included discharge mRS and mortality. Multivariate regression and IPTW matching were used for analyses.
Results:
Among 359 patients (median age 40; 68.5% female), 220 (61.3%) received UFH and 139 (38.7%) enoxaparin. Overall, only 64% of PTT values fell within the therapeutic range, and 24.9% received an initial UFH bolus. UFH was associated with worse outcomes at discharge (mRS 3–6: aOR 2.89; mRS 2–6: aOR 1.90, ordinal mRS aOR 1.56) and at 6 months (mRS 3–6: aOR 2.63). Poor recovery was independently linked to UFH-CRI and frequent infusion adjustments. Notably, in the sensitivity analysis limited to UFH patients with ≥50%, ≥67%, and ≥79% therapeutic PTT values, the outcome differences diminished. Age was identified as an independent predictor of UFH responsiveness, and female sex, elevated BMI, as predictors of increased number of changes in UFH infusion rate.
Conclusions:
In this international, multicenter cohort of patients with acute CVT, treatment with UFH was associated with worse clinical outcomes compared to 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.
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