Safety and Efficacy of Early Pharmacological Thromboprophylaxis in Traumatic Brain Injury: Systematic Review and Meta-Analysis

Abstract

Patients with traumatic brain injury (TBI) are at an increased risk of developing venous thromboembolic events (VTE). Pharmacological thromboprophylaxis (PTP) is routinely delayed because of concerns of exacerbating intracranial hemorrhage (ICH). The aim of this review is to examine the literature and assimilate suitable data to assess the safety and efficacy of PTP administered within 72 h in TBI patients. We systematically searched the literature for randomized controlled trials or cohort studies reporting on the timing of PTP in TBI. We dichotomized the timing of PTP to early and late at 72 h post-injury. The rates of VTE and ICH progression were our primary endpoints and were pooled using a fixed-effects model. A total of five retrospective cohort studies were included within the review including a total of 1624 patients, of which 713 received early PTP and 911 received late PTP. Within the early and late group there was a total of 43 and 106 VTE respectively, with a risk ratio of 0.52 (0.37, 0.73). Assessing safety, the relative risk of ICH progression in the early compared with the late PTP group was 0.64 (0.35, 1.14). Based on the available literature, we can tentatively conclude that early PTP (<72 h) reduces the risk of VTE without affecting progression of ICH. However, much work is yet to be done to better clarify ICH subtypes at risk of progression and the implementation of evidence-based guidelines backed up with randomized control trial level evidence.

Safety and Efficacy of Early Pharmacologic Thromboprophylaxis in Traumatic Brain Injury

“…A meta-analysis by the Brain Trauma Foundation in 2007 showed that there was insufficient evidence to guide the timing of PTP administration in TBI patients [12]. A recent meta-analysis was performed on randomized controlled trials or cohort studies that reported on the timing of PTP in TBI [13]. They also dichotomized the timing of PTP to early and late at 72 h post-injury.…”

“…Assessing safety, the relative risk of ICH progression in the early compared with the late PTP group was 0.64 (0.35, 1.14) [13]. If we add the number of patients from our study to the patients in the meta-analysis by Jamjoom and Jamjoom [13], this will add to 51 VTEs (6.4%) in 793 total patients in the < 72 h group versus 119 VTEs (12.4%) in 959 total patients in the > 72 h group.…”

“…If we add the number of patients from our study to the patients in the meta-analysis by Jamjoom and Jamjoom [13], this will add to 51 VTEs (6.4%) in 793 total patients in the < 72 h group versus 119 VTEs (12.4%) in 959 total patients in the > 72 h group. This would lead to similar results with a risk ratio of 0.52 (0.37, 0.73, P = 0.0002).…”

Early initiation of prophylactic heparin in severe traumatic brain injury is associated with accelerated improvement on brain imaging

“…[5678] Heparin derivatives (such as unfractionated heparin [UFH] or low molecular weight heparin [LMWH]) are often administered subcutaneously as prophylactic treatment when considered safe in the injured patient. [9] However, clinicians caring for patients with brain injury may be hesitant to administer these agents early after injury given the perceived risk of worsening intracranial hemorrhage. [1011]…”

What′s new in emergencies, trauma, and shock? Heparin in severe traumatic brain injury: Beyond venous thromboembolism prevention?

“…[11] Meta-analyses based on few studies with the abovementioned limitations, demonstrate that the use of unfractioned (UFH) or low molecular weights heparins (LMWHs) in the acute phase of spontaneous intracranial bleeding significantly reduce the risk of pulmonary embolism (PE) and overall mortality and nonsignificantly reduce the risk of deep vein thrombosis (DVT) without a significant increasing of hematoma enlargement or rebleeding, whereas the early administration of pharmacological prophylaxis in traumatic intracranial hemorrhage within 72 h from bleeding onset significantly reduce the risk of PE, DVT, and overall mortality without increasing the hematoma progression. [1213] The most recent available guidelines recommend to start the pharmacological prophylaxis of VTE in immobilized patients with STBI or ICH by using UFH or LMWHs after 48-72 h from bleeding onset and anyway when clinical and neuroradiological examination is stable. [1415]…”