Chemoprophylaxis for Venous Thromboembolism in Operative Treatment of Fractures of the Tibia and Distal Bones: A Systematic Review and Meta-analysis

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Clinical practice has shifted from therapeutic anticoagulation of any lower extremity venous thromboembolism (VTE) to only thromboses with risk of proximal extension or embolization—clinically important VTE (CIVTE). Isolated operative fractures of the tibia or distal bone of the lower extremity are associated with low-to-intermediate VTE risk, and there is wide variability in the choice to anticoagulate as well as anticoagulant. We sought to evaluate the role for chemoprophylaxis of VTE and CIVTE in these injuries by meta-analysis of Level I evidence.

Data Sources:

Articles in English, Chinese, French, and German in MEDLINE, Biosis, and EMBASE from 1988 to 2016.

Study Selection:

Randomized controlled trials describing chemoprophylaxis of VTE after operative management of fractures of the tibia and distal bones. Independent review of 1502 citations yielded 5 studies (1181 patients) meeting inclusion criteria.

Data Extraction:

Chemoprophylaxis regimen, VTE, CIVTE, and major bleeding events were recorded. Study quality was assessed with regard to randomization, outcome assessment allocation and treatment concealment, and commercial funding.

Data Synthesis:

A random-effects model meta-analysis determined that chemoprophylaxis with a low-molecular-weight heparin (LMWH) compared with placebo or no intervention significantly reduced the risk of any VTE [pooled relative risk (RR) = 0.696, 95% confidence interval (0.490–0.989), P = 0.043; homogeneity P = 0.818, I2 = 0%]. However, chemoprophylaxis with a LMWH compared with placebo did not significantly reduce the risk of CIVTE [RR = 0.865, 95% confidence interval (pooled RR = 0.112–3.863), P = 0.790; homogeneity P = 0.718, I2 = 0%]. No major bleeding events occurred. Funnel plots did not suggest publication bias. The number needed to treat was 31 patients treated with chemoprophylaxis using a LMWH to prevent 1 VTE and 584 patients to prevent 1 CIVTE.


Meta-analysis of Level I evidence suggests that routine postoperative anticoagulation after surgical management of an isolated fracture of the tibia or distal bone in patients without risk factors for VTE is unlikely to provide a clinical benefit, based on the absence of a treatment effect for preventing VTE warranting therapeutic anticoagulation.

Level of Evidence:

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

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