Low-Molecular-Weight Heparin Versus Unfractionated Heparin for Venous Thromboembolism Prophylaxis in Adult Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

BACKGROUND AND

OBJECTIVES

Traumatic brain injury (TBI) is associated with a high risk of venous thromboembolism (VTE), yet the optimal strategy for thromboprophylaxis remains uncertain. Low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) are commonly used agents in clinical practice, but their comparative effects in adult TBI have not been formally synthesized.

METHODS

Medical databases were searched through March 2026 for studies comparing LMWH and UFH for prophylaxis in adult patients with TBI. Randomized trials and cohort studies reporting at least one thromboembolic, hemorrhagic, or mortality outcome were included. Random-effects models were used to pool risk ratios (RR) with 95% CI. Risk of bias was assessed using Risk Of Bias In Non-randomized Studies of Interventions, and certainty of evidence was evaluated using Grading of Recommendations Assessment, Development, and Evaluation.

RESULTS

Twelve retrospective studies met the inclusion criteria. LMWH was associated with a lower risk of VTE than UFH (RR 0.59, 95% CI, 0.46-0.75; I2 = 41.82%). This pattern was consistent across thromboembolic outcomes, including deep vein thrombosis (RR 0.64, 95% CI, 0.53-0.79; I2 = 59.09%) and pulmonary embolism (PE) (RR 0.61, 95% CI, 0.56-0.67; I2 = 0%). Hemorrhagic outcomes also favored LMWH, including intracranial hemorrhage progression (RR 0.69, 95% CI, 0.50-0.96; I2 = 0%) and delayed craniectomy (RR 0.55, 95% CI, 0.42-0.72; I2 = 80.36%). In-hospital mortality was lower for LMWH (RR 0.50, 95% CI, 0.36-0.71; I2 = 83.36%). Certainty of evidence was moderate for VTE and PE, low for deep vein thrombosis and intracranial hemorrhage progression, and very low for delayed craniectomy and in-hospital mortality.

CONCLUSION

LMWH was associated with a lower thromboembolic risk than UFH, without evidence of increased hemorrhagic complications. These findings support consideration of LMWH as a preferred pharmacological prophylactic agent in appropriately selected patients. Prospective comparative studies are needed to determine whether this observed advantage is causal.