S. P. Myers1, J. B. Brown1, X. Chen1, C. E. Wade2,3,4, J. C. Cardenas2,3, M. D. Neal1 1University Of Pittsburgh,Division Of Trauma And General Surgery, Department Of Surgery,Pittsburgh, PA, USA 2McGovern Medical School at UTHealth,Division Of Acute Care Surgery, Department Of Surgery, McGovern School Of Medicine,Houston, TX, USA 3McGovern Medical School at UTHealth,Center For Translational Injury Research,Houston, TX, USA 4McGovern Medical School at UTHealth,Center For Translational And Clinical Studies,Houston, TX, USA
Introduction: Venous thromboembolic events (VTE) are common after severe injury, but factors predicting their timing remain incompletely understood. As the balance between hemorrhage and thrombosis is dynamic during a patient’s hospital course, early and late VTE may be physiologically discrete processes. We conducted a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial hypothesizing that risk factors would differ between early and late VTE.
Methods: A threshold for early and late events was determined by cubic spline analysis of VTE distribution. Univariate analysis determined association of delayed resuscitation with early or late VTE. Multinomial regression was used to analyze association of clinical variables with early or late VTE compared to no VTE adjusting for predetermined confounders including mortality, demographics, injury mechanism/severity, blood products, hemostatic adjuncts, and comorbidities. Serially collected coagulation assays were analyzed for differences that might distinguish between early and late VTE and no VTE.
Results: After plotting VTE distribution over time, cubic spline analysis established a threshold at 12 days corresponding to a change in odds of early versus late events (Figure 1). Multinomial regression revealed differences between early and late VTE. Variables associated with early but not late VTE included older age (RR 1.03; 95%CI 1.01, 1.05; p=0.01), femur fracture (RR 2.96; 95%CI 0.99, 8.84; p=0.05), chemical paralysis (RR 2.67; 95%CI 1.20, 5.92; p=0.02), traumatic brain injury (RR 14.17; 95%CI 0.94, 213.57; p=0.05), and plasma transfusion (RR 1.13; 95%CI 1.00, 1.28, p=0.05). In contrast, late VTE events were predicted by vasopressor use (RR 4.49; 95%CI 1.24, 16.30; p=0.02) and ICU length of stay (RR 1.11; 95%CI 1.02, 1.21; p=0.02). Sepsis increased risk of early (RR 3.76, 95% CI 1.71, 8.26; p<0.01) and late VTE (5.91; 95% CI 1.46, 23.81; p=0.01). Coagulation assays also differed between early and late VTE. Prolonged lag time (RR 1.05, 95% CI 0.99, 1.1; p=0.05) and time to peak thrombin generation (RR 1.03; 95% CI 1.00, 1.06; p=0.02) were associated with increased risk of early VTE alone. Delayed resuscitation approaching ratios of 1:1:1 for plasma, platelets, and red blood cells among patients randomized to 1:1:2 therapy was a risk factor for late (RR 6.69; 95% CI 1.25, 35.64; p=0.03) but not early VTE.
Conclusion: There is evidence to support that early and late thromboembolic events may differ in their pathophysiology and clinically relevant risk factors. Defining chronologic thresholds and clinical markers associated with temporal trends in VTE distribution may allow for a more individualized approach to thromboprophylaxis.
