Tranexamic acid administration is associated with an increased risk of posttraumatic venous thromboembolism

BACKGROUND Tranexamic acid (TXA) is used as a hemostatic adjunct for hemorrhage control in the injured patient and reduces early preventable death. However, the risk of venous thromboembolism (VTE) has been incompletely explored. Previous studies investigating the effect of TXA on VTE vary in their findings. We performed a propensity matched analysis to investigate the association between TXA and VTE following trauma, hypothesizing that TXA is an independent risk factor for VTE. METHODS This retrospective study queried trauma patients presenting to a single Level I trauma center from 2012 to 2016. Our primary outcome was composite pulmonary embolism or deep vein thrombosis. Mortality, transfusion, intensive care unit and hospital lengths of stay were secondary outcomes. Propensity matched mixed effects multivariate logistic regression was used to determine adjusted odds ratio (aOR) and 95% confidence intervals (95% CI) of TXA on outcomes of interest, adjusting for prespecified confounders. Competing risks regression assessed subdistribution hazard ratio of VTE after accounting for mortality. RESULTS Of 21,931 patients, 189 pairs were well matched across propensity score variables (standardized differences <0.2). Median Injury Severity Score was 19 (interquartile range, 12–27) and 14 (interquartile range, 8–22) in TXA and non-TXA groups, respectively (p = 0.19). Tranexamic acid was associated with more than threefold increase in the odds of VTE (aOR, 3.3; 95% CI, 1.3–9.1; p = 0.02). Tranexamic acid was not significantly associated with survival (aOR, 0.86; 95% CI, 0.23–3.25; p = 0.83). Risk of VTE remained elevated in the TXA cohort despite accounting for mortality (subdistribution hazard ratio, 2.42; 95% CI, 1.11–5.29; p = 0.03). CONCLUSION Tranexamic acid may be an independent risk factor for VTE. Future investigation is needed to identify which patients benefit most from TXA, especially given the risks of this intervention to allow a more individualized treatment approach that maximizes benefits and mitigates potential harms. LEVEL OF EVIDENCE Therapeutic, level III.

[1]  T. Rasmussen,et al.  Fibrinolysis in trauma: a review , 2018, European Journal of Trauma and Emergency Surgery.

[2]  E. Elster,et al.  Evaluation of Military Use of Tranexamic Acid and Associated Thromboembolic Events , 2017, JAMA surgery.

[3]  E. Haut,et al.  Does Tranexamic Acid Cause Venous Thromboembolism After Trauma?: Who Cares, If It Saves Lives? , 2017, JAMA surgery.

[4]  S. Shackford,et al.  The rate of deep vein thrombosis doubles in trauma patients with hypercoagulable thromboelastography , 2017, The journal of trauma and acute care surgery.

[5]  S. Kushimoto,et al.  Effectiveness of early administration of tranexamic acid in patients with severe trauma , 2017, The British journal of surgery.

[6]  K. Yamakawa,et al.  Tranexamic acid and trauma-induced coagulopathy , 2017, Journal of Intensive Care.

[7]  H. Ishikura,et al.  Trauma-induced coagulopathy and critical bleeding: the role of plasma and platelet transfusion , 2017, Journal of Intensive Care.

[8]  Eric J. Ley,et al.  Association Between Enoxaparin Dosage Adjusted by Anti-Factor Xa Trough Level and Clinically Evident Venous Thromboembolism After Trauma. , 2016, JAMA surgery.

[9]  R. Lefering,et al.  Prehospital administration of tranexamic acid in trauma patients , 2016, Critical Care.

[10]  A. Jerath,et al.  Tranexamic acid: a clinical review. , 2015, Anaesthesiology intensive therapy.

[11]  Timothy R. Smith,et al.  Time to Event Analysis for the Development of Venous Thromboembolism After Spinal Fusion ≥ 5 Levels. , 2015, World neurosurgery.

[12]  C. Wade,et al.  The impact of tranexamic acid on mortality in injured patients with hyperfibrinolysis , 2015, The journal of trauma and acute care surgery.

[13]  K. Willett,et al.  Tranexamic acid use in severely injured civilian patients and the effects on outcomes: a prospective cohort study. , 2015, Annals of surgery.

[14]  A. Peitzman,et al.  Design of the Study of Tranexamic Acid during Air Medical Prehospital Transport (STAAMP) Trial: Addressing the Knowledge Gaps , 2015, Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors.

[15]  C. Schulman,et al.  Do all trauma patients benefit from tranexamic acid? , 2014, The journal of trauma and acute care surgery.

[16]  P. Cameron,et al.  Tranexamic acid for trauma: Filling the ‘GAP’ in evidence , 2014, Emergency medicine Australasia : EMA.

[17]  A. Sauaia,et al.  Fibrinolysis greater than 3% is the critical value for initiation of antifibrinolytic therapy , 2013, The journal of trauma and acute care surgery.

[18]  S. Curley,et al.  Distinct predictors of pre- versus post-discharge venous thromboembolism after hepatectomy: analysis of 7621 NSQIP patients. , 2013, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[19]  R. Winfield,et al.  Dose adjusting enoxaparin is necessary to achieve adequate venous thromboembolism prophylaxis in trauma patients , 2013, The journal of trauma and acute care surgery.

[20]  Kristin L. Sainani Propensity Scores: Uses and Limitations , 2012, PM & R : the journal of injury, function, and rehabilitation.

[21]  M. Midwinter,et al.  Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. , 2012, Archives of surgery.

[22]  Peter J Pronovost,et al.  Surveillance bias in outcomes reporting. , 2011, JAMA.

[23]  M. Levi,et al.  Safety of recombinant activated factor VII in randomized clinical trials. , 2010, The New England journal of medicine.

[24]  A. McDonald,et al.  Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial , 2010, The Lancet.

[25]  Lesly A. Dossett,et al.  Early prediction of massive transfusion in trauma: simple as ABC (assessment of blood consumption)? , 2009, The Journal of trauma.

[26]  R. Maier,et al.  Patterns of Errors Contributing to Trauma Mortality: Lessons Learned From 2594 Deaths , 2006, Annals of surgery.

[27]  Rolf Lefering,et al.  Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. , 2006, The Journal of trauma.

[28]  J. Szalai,et al.  A prospective study of venous thromboembolism after major trauma. , 1994, The New England journal of medicine.

[29]  D. Rubin,et al.  Constructing a Control Group Using Multivariate Matched Sampling Methods That Incorporate the Propensity Score , 1985 .

[30]  M. Trutschl,et al.  Tranexamic Acid: Promise or Panacea The Impact of Air Medical Administration of Tranexamic Acid on Morbidity, Mortality, and Length of Stay , 2018, Advanced Emergency Nursing Journal.

[31]  G. Bochicchio,et al.  Tranexamic Acid Update in Trauma. , 2017, Critical care clinics.

[32]  A. Sauaia,et al.  Featured Articles for CME Credit December 2014 Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: The spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy , 2014 .

[33]  P. Pronovost,et al.  Duplex ultrasound screening for deep vein thrombosis in asymptomatic trauma patients: a survey of individual trauma surgeon opinions and current trauma center practices. , 2011, The Journal of trauma.