Platelet flux in trauma-associated venous thromboembolism: A secondary analysis of the Consortium of Leaders in the Study of Traumatic Thromboembolism (CLOTT) studies

BACKGROUND Venous thromboembolism (VTE) after traumatic injury is morbid. Evaluating changes in platelets in injured patients who develop VTE could identify platelet-based strategies for management of thrombotic complications after injury. METHODS In a prospectively designed secondary analysis of a multicenter cohort study conducted by the Consortium of Leaders in the Study of Traumatic Thromboembolism (CLOTT1) study group, injured patients aged 18 to 40 years admitted for a minimum of 48 hours with at least one risk factor for VTE were evaluated. A subset of CLOTT1 patients had platelet aggregometry and thromboelastography performed to examine platelet function (CLOTT2). Patients who developed VTE were compared with those who did not. RESULTS Of 7,805 patients from CLOTT1 (mean [SD] age, 29.1 [6.4] years; 1,987 [25.5%] female), 425 (5.4%) developed VTE. Platelet count was lower at each time point for patients with VTE (admission: 242 [234–251] vs. 254 [252–256], p < 0.01; hospital day 1: 157 [150–164] vs. 197 [195–198], p < 0.01; all counts ×10 9 /L). An initial 10-point reduction in platelet count was associated with development of VTE (odds ratio, 1.32 [1.13–1.53]; p < 0.01) controlling for shock, injury severity, coagulopathy, sex, and product transfusion. When evaluating 129 CLOTT2 patients, velocity of platelet aggregation was higher on admission in the VTE group (18.5 vs. 12.8 aggregation units/min; p < 0.01) in response to adenosine diphosphate stimulation. In response to thrombin stimulation, velocity of platelet aggregation was higher at 48 hours (34.4 vs. 12.3 aggregation units/min; p < 0.01), and overall aggregation was higher in the VTE group at 72 hours (area under the curve, 173.2 vs. 129.6; p < 0.01). Thromboelastography results were not different between groups. CONCLUSION This study identified an association of early reduction in platelet count with the development of VTE in injured patients at risk for VTE. P2Y 1/2 and protease-activated receptor 1 receptor stimulation changes in platelet aggregation responses are altered in VTE patients. Interrogating platelet count and functional responses may be beneficial in evaluating thrombotic complications after injury. LEVEL OF EVIDENCE Diagnostic Test/Criteria; Level III.