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

Abstract

Objective The objective of the study was Tto 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, IPA, Health Star and CINAHL 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 (VTE), hemorrhage, mortality or coagulation parameters with original analyses were eligible for the review. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 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 due to varying methodological design and quality of the studies. Twenty-one studies focused on the effects of pharmacological thromboprophylaxis (PTP) post-TBI on VTE and/or progression of intracranial hemorrhage (ICH) while two RCTs analyzed coagulation parameters as the result of anticoagulation. Conclusion PTP appears to be safe among TBI patients with stabilized hemorrhagic patterns. More evidence is needed regarding effectiveness of PTP in preventing VTE as well as preferred agent, dose and timing for PTP.

Early venous thromboembolism chemoprophylaxis in combat-related penetrating brain injury

“…15 The data regarding this intervention's role in preventing DVT and PE are also consistent with findings in that systematic review, which was unable to definitively show efficacy even after consideration of the full body of evidence currently in the literature. 15 One potential confounder is the influence of attending neurosurgeon preference and clinical judgment on the treatment decisions made. The evolution of combat neurotrauma care at KAF provided a natural experiment that, by chance, allocated patients approximately equally to 2 different treatment groups (early VTC and no early VTC) over the studied period.…”

“…5 A 2014 systematic review of over 20 studies also found that VTC is safe in TBI patients with stable hemorrhages, though the authors were unable to definitively comment on agent selection, dosage, first dose timing, or efficacy in preventing VTE. 15 We have previously described the spectra and mechanisms of brain injury, and their related complications, suffered during the conflicts in Iraq and Afghanistan. [1][2][3][4]7,16,17 These injuries and the circumstances surrounding the theater and medical evacuation care posed additional challenges for physicians caring for the wounded.…”

The Formation of Microthrombi in Parenchymal Microvessels after Traumatic Brain Injury Is Independent of Coagulation Factor XI

“…In fact, patients suffering from brain trauma are often immobilized for significant periods of time and require anti-coagulation. 27,28 However, almost 50% of all TBI patients also have intracranial bleeding, thereby making the choice of the appropriate anticoagulant rather difficult. 29 Therefore, an additional aim of the current study was to investigate whether inhibition of FXI increases hemorrhage after TBI or if it has a favorable risk profile.…”

“…Since 14E11 has been shown to be antithrombotic in rodent and primate models, 37,38 this is of particular importance regarding a second therapeutic approach: the safe prophylactic anticoagulation, which is required, for example, in patients who are immobilized in an intensive care unit; this is usually the case in the first days or weeks following TBI. 27,28 Until now, prophylactic anticoagulation in patients suffering from TBI remains a double edged sword 27,28,[61][62][63][64][65][66][67] : there is the risk of secondary thrombosis due to immobilization and altered coagulation after TBI versus the risk of exacerbating intracranial hemorrhage. After inhibiting FXI activation by FXIIa with 14E11 in our CCI model, we specifically determined intracranial hemorrhage and could not detect any detrimental effect 15 min or 24 h after trauma.…”

“…56 Despite these promising results, a safe clinical therapy directed against microclot formation following TBI is still missing. 27,28 With our approach of inhibiting FXI activation, we specifically aimed to decrease post-trauma microthrombus formation without exacerbating intracranial bleeding complications. Since the intrinsic cascade is mainly important for the amplification of coagulation 57,58 we targeted a coagulation factor from this cascade for our therapy.…”