According to an American Association for the Surgery of Trauma (AAST) Critical Care Committee Clinical Consensus Document published in 2021, either unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) may be used for venous thromboembolism (VTE) prophylaxis in patients with traumatic brain injury (TBI), although LMWH may offer advantages. Analyses of the Trauma Quality Improvement Program (TQIP) database demonstrated lower pulmonary embolism rates with LMWH compared with UFH, including in patients with severe or isolated TBI, and identified UFH as an independent predictor of VTE and mortality. Importantly, LMWH was not associated with an increased risk of unplanned neurosurgical intervention. Despite these findings, limitations of retrospective database studies and variability in injury characteristics preclude a definitive recommendation, and current Brain Trauma Foundation guidelines continue to support either agent. Although the use of UFH has decreased over time, it may still be favored by some for TBI patients due to a theoretical benefit of shorter half-life. [1]
Per a 2020 Western Trauma Association (WTA) management algorithm on pharmacologic prophylaxis for VTE in trauma patients, enoxaparin is recommended for most trauma patients, with higher doses now considered standard of care. Enoxaparin is the preferred agent for most trauma patients due to its favorable pharmacokinetic and pharmacodynamic profile, including greater bioavailability, longer half-life, and more predictable anticoagulant effect compared with unfractionated heparin, as well as lower rates of platelet interaction, heparin-induced thrombocytopenia, and osteoporosis. However, in patients with end-stage renal disease or severe renal impairment (creatinine clearance <30 mL/min), enoxaparin should be avoided due to renal clearance and increased bleeding risk In TBI and spine trauma populations, enoxaparin is associated with lower VTE rates and improved survival compared with unfractionated heparin, without increased progression of brain injury regardless of timing of initiation. A starting dose of enoxaparin 30 mg twice daily is recommended for patients with brain or spine trauma, with consideration of anti-Xa–guided dose adjustment. [2]
The 2024 American College of Surgeons Best Practice Guidelines recommend low–molecular-weight heparin over unfractionated heparin for VTE prophylaxis in trauma patients and identify LMWH as the preferred agent for patients with traumatic brain injury, including those with intracranial pressure monitors. Available evidence indicates that LMWH is associated with lower VTE rates and similar rates of intracranial hemorrhage progression compared with UFH in both operative and nonoperative TBI populations. While enoxaparin 40 mg every 12 hours is considered best practice in general trauma patients, data is limited in TBI patients and the expert panel recommends a lower initial dose of 30 mg every 12 hours in this population. When UFH is used instead, a dosing regimen of 5,000 units subcutaneously every 8 hours is recommended. [3]
A 2022 clinical protocol developed by stakeholders from the American Association for the Surgery of Trauma (AAST) and the American College of Surgeons–Committee on Trauma (ACS-COT) sought to standardize VTE prophylaxis in trauma patients and identifies enoxaparin as the preferred pharmacologic agent, with higher dosing now considered standard of care. For most trauma patients, an initial dose of enoxaparin 40 mg twice daily is recommended, as 30 mg twice daily may provide inadequate prophylaxis and is associated with higher VTE rates. However, a reduced starting dose of 30 mg twice daily is advised for select populations, including patients older than 65 years, those weighing less than 50 kg, or those with a creatinine clearance of 30–60 mL/min, as well as patients with traumatic brain injury, spinal cord injury, or pregnancy, due to limited dosing data in these groups. Unfractionated heparin is reserved for patients with significant renal impairment, defined as a creatinine clearance below 30 mL/min. [4]
A 2025 review evaluated the comparative safety and efficacy of unfractionated heparin (UFH) versus low-molecular-weight heparin (LMWH), specifically enoxaparin, for venous thromboembolism (VTE) prophylaxis in patients with traumatic brain injury (TBI). The review synthesized evidence from 70 experimental and observational studies, including large trauma registry analyses, and assessed outcomes such as VTE incidence, mortality, intracranial hemorrhage progression, and need for neurosurgical intervention. Across multiple analyses from the Trauma Quality Improvement Program (TQIP), LMWH was associated with significantly lower risks of VTE and mortality compared with UFH, with one study demonstrating reduced odds of VTE (odds ratio [OR] 0.67; 95% confidence interval [CI] 0.53–0.84) and death (OR 0.64; 95% CI 0.49–0.83). Importantly, LMWH did not increase rates of unexpected neurosurgical intervention compared with UFH when initiated after stable repeat computed tomography (CT) imaging. Although early studies raised concern for hemorrhage progression with LMWH, subsequent analyses suggested these findings were largely attributable to greater injury severity in patients receiving LMWH. Based on the totality of evidence, the authors concluded that LMWH is superior to UFH for trauma deep vein thrombosis prophylaxis in TBI patients, providing improved VTE prevention and survival without a clinically meaningful increase in intracranial bleeding risk when appropriately timed. [5]
A 2022 meta-analysis meticulously evaluated the efficacy and safety of low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) for the prevention of venous thromboembolism (VTE) in trauma patients. This comprehensive systematic review included data spanning from inception through March 12, 2021, and utilized six distinct databases to gather relevant randomized controlled trials (RCTs) and observational studies. The meta-analysis incorporated four RCTs comprising 879 patients and eight observational studies involving 306,747 patients, including two studies limited to isolated head trauma and one study limited to isolated spinal trauma. The methodical approach involved pooling effect estimates using a random-effects model and inverse variance weighting, ensuring a robust synthesis of evidence. The risk of bias was stringently assessed using the Cochrane tool for RCTs and the ROBINS-I tool for observational studies, with the certainty of findings evaluated through the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. The results demonstrated that LMWH significantly reduced the risk of deep vein thrombosis (DVT) and overall VTE compared with UFH (RR 0.67 and 0.68, respectively; moderate certainty). LMWH also showed potential reductions in pulmonary embolism and mortality, though these findings were supported by lower-certainty evidence. Safety outcomes, including adverse events and heparin-induced thrombocytopenia, remained uncertain due to very low-certainty evidence. Overall, the analysis supports the superiority of LMWH over UFH for VTE prevention in trauma patients while underscoring the need for further research to better define its safety profile. [6]
A 2009 systematic review meticulously evaluated the treatment modalities for deep venous thromboembolism (DVT) following spinal cord injury. The research encompassed a comprehensive assessment of published literature from 1980 to 2007. The study's methodology involved the analysis of randomized controlled trials (RCTs) and non-randomized studies. Studies were only included if they involved at least three subjects with spinal cord injury and a clear intervention was being scrutinized, culminating in the detailed review of around 700 articles from an initial 17,000 titles. Results revealed substantial evidence supporting the use of low molecular weight heparin (LMWH) over unfractionated heparin (UFH) in reducing venous thromboembolic events in spinal cord injury patients. While LMWH demonstrated a lower incidence of bleeding complications, UFH at adjusted higher doses showed efficacy yet increased bleeding risk. Furthermore, the review detailed mechanical prophylaxis measures such as pneumatic compression and gradient elastic stockings, which were suggested to diminish the risk of thromboembolism, although the evidence supporting these methods was less robust compared to pharmacologic approaches. The paper underscored the importance of combining pharmacologic measures with mechanical strategies to enhance prophylactic effectiveness, especially when initiated early in the treatment phase post-injury. [7]
A 2023 international cross-sectional survey evaluated current practices for venous thromboembolism (VTE) prophylaxis in trauma patients and assessed alignment with contemporary guidelines, including those from EAST and the WTA. The 38-item survey, distributed through the American Association for the Surgery of Trauma (AAST), yielded 118 complete responses from 98 institutions. Most respondents reported guideline-concordant practice, with 81.4% using recommended enoxaparin-based regimens in non-obese patients with preserved renal function; enoxaparin 30 mg subcutaneously every 12 hours was the most commonly reported regimen (67.8%). Dose adjustment for obesity was common (74.6%), and two-thirds of respondents (66.1%) routinely used anti–factor Xa levels to guide dosing. For patients with renal dysfunction, the majority (68.6%) reported using unfractionated heparin, typically dosed at 5,000 units every 8 or 12 hours. [8]