Early versus Late Pharmacologic Thromboprophylaxis in Traumatic Brain Injury: A Propensity-Score Matched Cohort Study

Abstract

The optimal timing of pharmacological thromboprophylaxis in traumatic brain injury (TBI) remains uncertain due to competing risks of thrombosis and bleeding. This study evaluated whether early heparin initiation (≤72 hours) reduces vascular occlusive events (VOEs), mortality, and hospital stay without increasing bleeding. We compared early versus late (>72 hours) heparin use via propensity score matching (PSM), subgroup analyses, and multivariable logistic regression. Outcomes included VOEs (deep vein thrombosis, pulmonary embolism, myocardial infarction, and ischemic stroke), bleeding, 30- and 180-day mortality, and length of stay. After PSM, late heparin was associated with higher VOEs (25.16 vs. 12.24%, p < 0.001), 30-day mortality (20 vs. 11.89%, p = 0.03), 180-day mortality (32.26 vs. 19.58%, p = 0.004), and prolonged hospitalization (median: 15.7 vs. 9.7 days, p < 0.001), without increased bleeding risk (16.77 vs. 22.03%, p = 0.24). Subgroup analyses revealed late heparin as an independent risk factor for VOEs in mild TBI (odds ratio: 2.62, 95% confidence interval: 1.54–4.45; p < 0.001) regardless of fracture status, coagulation profile, or hemorrhagic classification, with nonsignificant associations in nonhemorrhagic and moderate-to-severe TBI subgroups. Multivariable analysis identified late heparin, higher comorbidity index, elevated platelet count, and cranial surgery as independent predictors of VOEs, with late heparin also independently associated with increased mortality. These findings suggest early heparin initiation reduces thromboembolic complications, mortality, and hospital stay without markedly increasing bleeding risk, supporting early anticoagulation in selected patients following individualized risk-benefit assessment.