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Timing Is Everything: Initiation of VTE Prophylaxis Within 24 Hours Following Major Trauma Is Effective and Safe
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Andrew J. Kerwin MD1, *Saskya Byerly
1, *Dina Filiberto
1, *Emily Lenart
1, Martin Croce
1, Ernest Moore
2, Margaret Knudson
31Surgery, University of Tennessee Health Science Center, Memphis, TN; 2Surgery, University of Colorado School of Medicine, Denver, CO; 3Surgery, University of California, San Francisco, San Francisco, CA
OBJECTIVE: Venous thromboembolism (VTE) is a major cause of morbidity and mortality following trauma, but early pharmacologic prophylaxis is often withheld for fear of bleeding complications. We hypothesized that initiation of pharmacologic VTE prophylaxis within 24 hours of admission for major trauma patients at risk for VTE would reduce VTE without increasing secondary bleeding complications.
METHODS: The Consortium of Leaders of the study of post-Traumatic Thromboembolism (CLOTT) is a prospective, observational, cohort, multicenter study conducted at 17 US level 1 trauma centers between 2018–2020 on patients aged 18-40 to examine the prevention and management of VTE. Patients were stratified by time to VTE prophylaxis initiation [< 24 hours (EARLY) or > 24 hours (LATE)] and compared. VTE, VTE prophylaxis agents, and bleeding complications secondary to VTE prophylaxis were analyzed. A generalized linear mixed model (GLMM) was performed to identify predictors of VTE.
RESULTS: 7,880 patients were prospectively enrolled. After excluding patients with a history of VTE, anticoagulants on admission, no prophylaxis during hospitalization, and early deaths, there were 3,369 in the EARLY group and 3,200 in the LATE group. Median age, initial systolic blood pressure (SBP), Glasgow Coma Scale (GCS) score, and sex were similar between groups. Blunt injury (82% vs 69%, p<0.001) and severe traumatic brain injury (TBI) (44% vs 12%) were more common in the LATE group. The LATE group had a higher ISS (20 vs 13; p<0.001) and longer ICU LOS (3 vs 0 days; p<0.001). ICU-free days were similar between groups. More LATE group patients developed VTE (7.8% vs 2.8%; p<0.001). Of 251 patients with VTE, deep venous thrombosis (DVT) alone [181 (72%) vs 61 (65%)], pulmonary embolism (PE) alone [46 (18%) vs 22 (23%)] and DVT and PE [24 (10%) vs 11 (12%)] were present more frequently in the LATE compared to EARLY group. The LATE group had a higher incidence of increased or new intracranial hemorrhage after prophylaxis initiation (0.5% vs 0.2%; p=0.009) and higher mortality (1.8% vs 0.6%; p<0.001). GLMM demonstrated EARLY VTE prophylaxis was associated with a lower risk of VTE (OR 0.58;95%CI 0.44–0.78; p<0.001), after controlling for covariates. Risk factors for VTE included penetrating injury, lower initial SBP and GCS score, higher ISS and transfusions within the first 24 hours. VTE was 1.9 times more likely to occur when heparin was the prophylactic agent as compared to enoxaparin.
CONCLUSIONS: In this CLOTT study, the largest prospective, multicenter observational study of the management of VTE following trauma, initiation of VTE prophylaxis within the first 24 hours after admission in trauma patients resulted in a 42% reduction of the risk of VTE without increased risk of bleeding. Given the significance of these data, initiation of VTE prophylaxis within 24 hours of admission for major trauma patients, including those with TBI, should be considered the standard of care.
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