Association of timing and agent for venous thromboembolism prophylaxis in patients with severe traumatic brain injury on venous thromboembolism events, mortality, neurosurgical intervention, and discharge disposition.

Background: Trauma patients are at increased risk for venous thromboembolism events (VTEs). The decision of when to initiate VTE chemoprophylaxis (VTEP) and with what agent remains controversial in patients with severe traumatic brain injury (TBI).
Methods: This comparative effectiveness study evaluated the impact of timing and agent for VTEP on outcomes for patients with severe TBI (Abbreviated Injury Scale head score of 3, 4, or 5). Data were collected at 35 Level 1 and 2 trauma centers from January 1, 2017, to June 1, 2022. Patients were placed into analysis cohorts: no VTEP, low-molecular-weight heparin (LMWH) ≤48 hours, LMWH >48 hours, heparin ≤48 hours, and heparin >48 hours. Propensity score matching accounting for patient factors and injury characteristics was used with logistic regression modeling to evaluate in-hospital mortality, VTEs, and discharge disposition. Neurosurgical intervention after initiation of VTEP was used to evaluate extension of intracranial hemorrhage.
Results: Of 12,879 patients, 32% had no VTEP, 36% had LMWH, and 32% had heparin. Overall mortality was 8.3% and lowest among patients receiving LMWH ≤48 hours (4.1%). Venous thromboembolism event rates were lower with use of LMWH (1.6% vs. 4.5%; odds ratio, 2.98; 95% confidence interval, 1.40-6.34; p = 0.005) without increasing mortality or neurosurgical interventions. Venous thromboembolism event rates were lower with early prophylaxis (2.0% vs. 3.5%; odds ratio, 1.76; 95% confidence interval, 1.15-2.71; p = 0.01) without increasing mortality ( p = 1.0). Early VTEP was associated with more nonfatal intracranial operations ( p < 0.001). However, patients undergoing neurosurgical intervention after VTEP initiation had no difference in rates of mortality, withdrawal of care, or unfavorable discharge disposition ( p = 0.7, p = 0.1, p = 0.5).
Conclusion: In patients with severe TBI, LMWH usage was associated with lower VTE incidence without increasing mortality or neurosurgical interventions. Initiation of VTEP ≤48 hours decreased VTE incidence and increased nonfatal neurosurgical interventions without affecting mortality. Low-molecular-weight heparin is the preferred VTEP agent for severe TBI, and initiation ≤48 hours should be considered in relation to these risks and benefits.
Level of Evidence: Therapeutic/Care Management; Level III.
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