Early Venous Thromboembolism Prophylaxis in Patients with Trauma Intracranial Hemorrhage: Analysis of the Prospective Multicenter CLOTT Study

BACKGROUND The optimal time to initiate venous thromboembolism prophylaxis (VTEp) for patients with intracranial hemorrhage (ICH) is controversial and must balance the risks of VTE with potential progression of ICH. We sought to evaluate the efficacy and safety of early VTEp initiation after traumatic ICH. METHODS This is a secondary analysis of the prospective multicenter Consortium of Leaders in the Study of Thromboembolism study. Patients with head Abbreviated Injury Scale score of > 2 and with immediate VTEp held because of ICH were included. Patients were divided into VTEp ≤ or >48 hours and compared. Outcome variables included overall VTE, deep vein thrombosis (DVT), pulmonary embolism, progression of intracranial hemorrhage (pICH), or other bleeding events. Univariate and multivariate logistic regressions were performed. RESULTS There were 881 patients in total; 378 (43%) started VTEp ≤48 hours (early). Patients starting VTEp >48 hours (late) had higher VTE (12.4% vs. 7.2%, p = 0.01) and DVT (11.0% vs. 6.1%, p = 0.01) rates than the early group. The incidence of pulmonary embolism (2.1% vs. 2.2%, p = 0.94), pICH (1.9% vs. 1.8%, p = 0.95), or any other bleeding event (1.9% vs. 3.0%, p = 0.28) was equivalent between early and late VTEp groups. On multivariate logistic regression analysis, VTEp >48 hours (odds ratio [OR], 1.86), ventilator days >3 (OR, 2.00), and risk assessment profile score of ≥5 (OR, 6.70) were independent risk factors for VTE (all p < 0.05), while VTEp with enoxaparin was associated with decreased VTE (OR, 0.54, p < 0.05). Importantly, VTEp ≤48 hours was not associated with pICH (OR, 0.75) or risk of other bleeding events (OR, 1.28) (both p = NS). CONCLUSION Early initiation of VTEp (≤48 hours) for patients with ICH was associated with decreased VTE/DVT rates without increased risk of pICH or other significant bleeding events. Enoxaparin is superior to unfractionated heparin as VTE prophylaxis in patients with severe TBI. LEVEL OF EVIDENCE Therapeutic/Care Management; Level IV.