Does tranexamic acid increase venous thromboembolism risk among trauma patients? A prospective multicenter analysis across 17 level I trauma centers

Importance: The early use of tranexamic acid (TXA) has demonstrated benefit among some trauma patients in hemorrhagic shock. The association between TXA administration and thromboembolic events (including deep vein thrombosis (DVT), pulmonary embolism (PE) and pulmonary thrombosis (PT)) remains unclear. We aimed to characterize the risk of venous thromboembolism (VTE) subtypes among trauma patients receiving TXA and to determine whether TXA is associated with VTE risk and mortality. Methods: We analyzed a prospective, observational, multicenter cohort data from the Consortium of Leaders in the Study of Traumatic Thromboembolism (CLOTT) study group. The study was conducted across 17 US level I trauma centers between January 1, 2018, and December 31,2020. We studied trauma patients ages 18–40 years, admitted for at least 48 h with a minimum of 1 VTE risk factor and followed until hospital discharge or 30 days. We compared TXA recipients to non-recipients for VTE and mortality using inverse probability weighted Cox models. The primary outcome was the presence of documented venous thromboembolism (VTE). The secondary outcome was mortality. VTE was defined as DVT, PE, or PT. Results: Among the 7,331 trauma patients analyzed, 466 (6.4%) received TXA. Patients in the TXA group were more severely injured than patients in the non-TXA group (ISS 16+: 69.1% vs. 48.5%, p < 0.001) and a higher percentage underwent a major surgical procedure (85.8% vs. 73.6%, p < 0.001). Among TXA recipients, 12.5% developed VTE (1.3% PT, 2.4% PE, 8.8% DVT) with 5.6% mortality. In the non-TXA group, 4.6% developed VTE (1.1% PT, 0.5% PE, 3.0% DVT) with 1.7% mortality. In analyses adjusting for patient demographic and clinical characteristics, TXA administration was not significantly associated with VTE (aHR 1.00, 95%CI: 0.69–1.46, p = 0.99) but was significantly associated with increased mortality (aHR 2.01, 95%CI: 1.46–2.77, p < 0.001). Conclusion: TXA was not clearly identified as an independent risk factor for VTE in adjusted analyses, but the risk of VTE among trauma patients receiving TXA remains high (12.5%). This supports the judicious use of TXA in resuscitation, with consideration of early initiation of DVT prophylaxis in this high-risk group.