The effectiveness and safety of pharmacological prophylaxis against venous thromboembolism in patients with moderate to severe traumatic brain injury: A systematic review and meta-analysis

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Venous thromboembolism (VTE) is a common, potentially fatal complication after traumatic brain injury (TBI). The objective was to evaluate the effectiveness and safety of pharmacologic VTE prophylaxis in moderate to severe TBI patients, and its use in hospitals.


A systematic review of the literature was conducted using Medline, Embase, Central database, Google scholar, and the SciELO from 1966 to 2014.


All studies providing information on the following variables—use of VTE prophylaxis (both pharmacological and nonpharmacological), initiation of treatment, application of specific protocols, rates of VTE and hemorrhagic progression of the traumatic brain injury on computed tomographic scan—were included. The random effects model was used to calculate pooled effect estimates. Heterogeneity among studies was assessed using the Cochran Q homogeneity test. A forest plot was constructed, and aggregate odds ratio was computed. Potential publication bias was evaluated using funnel plots.


A total of 12 retrospective observational studies were identified, totaling 8,747 patients. Six studies (3,325 patients) were used to analyze the safety and five (2,105 patients) to analyze the effectiveness of pharmacological versus nonpharmacological prophylaxis, without considering the timing of treatment. Four studies (1,371 patients) were used to evaluate early versus late pharmacologic prophylaxis, with results favoring early administration (odds ratio, 0.46; 95% confidence interval, 0.24–0.88; p < 0.05; I2, 46%) and showing no significant differences regarding safety. Three studies (4,133 patients), used to analyze VTE prophylaxis protocols, showed significant heterogeneity (p < 0.01).


When we compared mechanical and pharmacological prophylaxis, the results were heterogeneous; and thus, their potential differences could not be assessed. In some studies, the introduction of prophylaxis protocols in neurocritical patient care improved their effectiveness. Early pharmacologic prophylaxis, in the first 72 hours after TBI, was more effective than late, when there was no hemorrhagic progression within 24 hours after injury; no significant differences were found regarding safety.


Systematic review/meta-analysis, level III.

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