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A Systematic Review of the Benefits and Risks of Anticoagulation Following Traumatic Brain Injury

Shen, Xian MS; Dutcher, Sarah K. PhD; Palmer, Jacqueline PharmD; Liu, Xinggang MD, PhD; Kiptanui, Zippora MPH; Khokhar, Bilal MA; Al-Jawadi, Mohammad H. PharmD; Zhu, Yue MS; Zuckerman, Ilene H. PharmD, PhD

Journal of Head Trauma Rehabilitation: July/August 2015 - Volume 30 - Issue 4 - p E29–E37
doi: 10.1097/HTR.0000000000000077
Original Articles

Objective: To synthesize the existing literature on benefits and risks of anticoagulant use after traumatic brain injury (TBI).

Design: Systematic review. A literature search was performed in MEDLINE, International Pharmaceutical Abstracts, Health Star, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) on October 11, 2012, and updated on September 2, 2013, using terms related to TBI and anticoagulants.

Main Measures: Human studies evaluating the effects of post-TBI anticoagulation on venous thromboembolism, hemorrhage, mortality, or coagulation parameters with original analyses were eligible for the review. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline was followed throughout the conduct of the review.

Results: Thirty-nine eligible studies were identified from the literature, of which 23 studies with complete information on post-TBI anticoagulant use and patient outcomes were summarized in this review. Meta-analysis was unwarranted because of varying methodological design and quality of the studies. Twenty-one studies focused on the effects of pharmacological thromboprophylaxis (PTP) post-TBI on venous thromboembolism and/or progression of intracranial hemorrhage, whereas 2 randomized controlled trials analyzed coagulation parameters as the result of anticoagulation.

Conclusion: Pharmacological thromboprophylaxis appears to be safe among TBI patients with stabilized hemorrhagic patterns. More evidence is needed regarding effectiveness of PTP in preventing venous thromboembolism as well as preferred agent, dose, and timing for PTP.

Department of Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, Baltimore (Mss Shen and Kiptanui, Drs Dutcher, Palmer, Liu, Al-Jawadi, and Zuckerman, and Mr Khokhar); Department of Surgery, University of Maryland, Baltimore (Mr Zhu); and IMPAQ International, Columbia, MD (Dr Zuckerman).

Corresponding Author: Ilene H. Zuckerman, PharmD, PhD, IMPAQ International, 10420 Little Patuxent Parkway, Suite 300, Columbia, MD 21044 (

The project was supported by National Institutes of Health 1 R21 AG042768-01. Bilal R. Khokhar is supported by NIA Epidemiology of Aging Training Program (2T32AG000262-16). Sarah K. Dutcher is supported by a Ruth L. Kirschstein NRSA predoctoral fellowship (F31 AG044091).

The authors thank Dr Yuen Tsang for his contribution to the assessment of study quality.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

The authors declare no conflicts of interest.

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