Safety of early chemoprophylaxis for venous thromboembolism after traumatic brain injury: a systematic review and meta-analysis. A military traumatic brain injury initiative study.

Objective: There is continuing uncertainty about the safety of early chemoprophylaxis for venous thromboembolism (VTE) in patients with traumatic brain injury (TBI). The objective of this paper was to 1) calculate the risk of progression of posttraumatic intracranial hemorrhage (ICH) after VTE chemoprophylaxis, and 2) compare the probability of ICH progression in early versus late VTE prophylaxis.

Methods: The authors searched for English-language literature from database inception to January 2023. Two independent reviewers selected studies on post-TBI VTE chemoprophylaxis in hospitalized patients. Study parameters included ICH progression (as determined by follow-up imaging after starting chemoprophylaxis) in relation to use versus nonuse, timing, and type of VTE chemoprophylaxis. Pertinent variables included author, year, study type, demographic variables, cranial and systemic Injury Severity Scores, and data documenting ICH progression or indirect evidence of TBI worsening after the initiation of VTE chemoprophylaxis.

Results: Thirty studies fulfilled the inclusion criteria. There was a 7.0% (95% CI 4.0%-10.0%) risk of CT-documented ICH progression following VTE chemoprophylaxis in the prophylactically treated group. There was no difference between the early versus late VTE prophylaxis groups for ICH progression (12 studies; OR 0.79 [95% CI 0.56-1.12]). There was also no significant difference in CT-documented ICH progression between the prophylactically treated and nontreated groups (5 studies; OR 0.57 [95% CI 0.28-1.18]).

Conclusions: The review of the literature shows that VTE chemoprophylaxis 72 hours after TBI is considered safe by the majority of authors. This meta-analysis did not reveal any evidence of increased risk of ICH when starting VTE chemoprophylaxis earlier, i.e., within 72 hours of TBI; however, it is important to emphasize that only a small number of lower-quality studies addressed the 48-hour or 24-hour time point. A randomized noninferiority trial should be the next step in answering the question of early (within 72 hours) VTE chemoprophylaxis after TBI.