Characterizing the delays in adequate thromboprophylaxis after TBI

Abstract

BackgroundWe sought to compare enoxaparin dosing for venous thromboembolism (VTE) prophylaxis in trauma patients with and without traumatic brain injury (TBI) to better understand the time and dose required to reach target anti-Xa levels. Our hypothesis was that patients with TBI have significant delays in the initiation of adequate pharmacological prophylaxis and require a higher enoxaparin dose than currently recommended.MethodsThe medical records of trauma patients who received enoxaparin dosing based on anti-Xa trough levels between August 2014 and October 2016 were reviewed. Patients were included if their anti-Xa trough level reached the target range (0.1 IU/mL to 0.2 IU/mL).ResultsA total of 163 patients had anti-Xa levels within the target range of which 41 (25.2%) had TBI. Patients with TBI had longer delays before initiating enoxaparin (7.5 days vs. 1.5 days after admission, p<0.01) and were more likely to receive unfractionated heparin prior to enoxaparin (46.3% vs. 11.5%, p<0.01). Anti-Xa levels reached the target range later in patients with TBI (11 days vs. 5 days after admission, p<0.01). Enoxaparin 40 mg two times per day was the median dose required to reach the target anti-Xa levels for both cohorts. VTE rates were higher among patients with TBI (22.0% vs. 9.0%, p=0.03). Four patients (9.8%) had progression of their intracranial hemorrhage prior to receiving enoxaparin, although none progressed during enoxaparin administration.ConclusionAmong patients with TBI who reached target anti-Xa levels, 11 days after admission were required to reach a median enoxaparin dose of 40 mg two times per day. Unfractionated heparin was used as pharmacological prophylaxis in about half of these patients. The delay in reaching the target anti-Xa levels and the use of unfractionated heparin likely contribute to the higher VTE rate in patients with TBI.Level of evidenceLevel III, therapeutic.

Relationship between anti-Xa level achieved with prophylactic low-molecular weight heparin and venous thromboembolism in trauma patients: A systematic review and meta-analysis

“…Dose adjustment based on anti-Xa alone may inadequately reduce VTE rates because waiting for the first anti-Xa level delays dose optimization. Studies have demonstrated that when dosing VTEp is based on anti-Xa, an additional 3.5 days elapses prior to achieving dose adequacy 43 ; this delay may explain why VTE rates are not necessarily reduced with an anti-Xa–based LMWH dosing strategy. Alternatively, this finding may suggest that anti-Xa levels simply describe a patient's thrombotic state at a given time, and are not a reliable indicator of VTEp over the entire episode.…”

“…blinded to the studies being assessed, with disagreements resolved by consensus or third-party adjudication. Included nonrandomized studies were assessed for quality using the Methodological Index for Nonrandomized Studies (MINORS) 43 …”

“…Included nonrandomized studies were assessed for quality using the Methodological Index for Nonrandomized Studies (MINORS). 43…”

Novel therapeutic medications for venous thromboembolism prevention in trauma patients: Findings from the Consensus Conference to Implement Optimal Venous Thromboembolism Prophylaxis in Trauma

“…There are challenges with initiating and dosing chemoprophylaxis in trauma patients with traumatic brain injury, spinal injury, and solid organ injuries even with current regimens. [37][38][39] Establishing that oral agents are safe in these specific injuries and in patients with multiple injury will require further studies.…”

“…The heterogeneity of injury patterns and bleeding risk after major trauma make generalized recommendations regarding the optimal novel chemoprophylactic strategy difficult to define and implement. There are challenges with initiating and dosing chemoprophylaxis in trauma patients with traumatic brain injury, spinal injury, and solid organ injuries even with current regimens 37–39 . Establishing that oral agents are safe in these specific injuries and in patients with multiple injury will require further studies.…”