Platelets retain inducible alpha granule secretion by P-selectin expression but exhibit mechanical dysfunction during trauma-induced coagulopathy.

Essentials Platelets in trauma-induced coagulopathy (TIC) are impaired, but the mechanism is not known. We performed comprehensive longitudinal platelet function testing in trauma patient samples. Platelets in TIC are widely impaired early after injury, but platelet activatability is intact. This suggests a mechanism of transient platelet cytoskeletal/integrin dysfunction during TIC. SUMMARY: Background Trauma-induced coagulopathy (TIC) is a common and deadly bleeding disorder. Platelet dysfunction is present during TIC, but its mechanisms remain unclear. Platelets are currently thought to become "exhausted," a state in which they have released their granule contents and can no longer aggregate or contract. Methods This prospective observational cohort study tested the hypothesis that platelet exhaustion is present during TIC and characterized the early time course of platelet dysfunction. Blood was collected from 95 adult trauma patients at a Level I trauma center at time of Emergency Department arrival and several time points over 72 h. Platelet activation state and function were characterized using CD62P (P-selectin) and PAC-1 surface membrane staining, platelet function analyzer (PFA-100), aggregometry, viscoelastic platelet mapping, and, to test for exhaustion, their ability to express CD62P after ex vivo adenosine diphosphate (ADP) agonism. Platelet function was compared between patients with and without TIC, defined by prothrombin time ≥18 s. Results Platelets in TIC showed no initial increase in their level of surface activation markers or impairment of their capacity to express CD62P in response to ADP stimulation. However, TIC platelets were impaired in nearly all functional assays, spanning adhesion, aggregation, and contraction. These effects largely remained after controlling for platelet count and fibrinogen concentration and resolved after 8 h. Conclusion The TIC platelets exhibit early impairment of adhesion, aggregation, and contraction with retained alpha granule secretion ability, suggesting a specific mechanism of cytoskeletal or integrin dysfunction that is not a result of more general platelet exhaustion.

Clot Formation Is Associated With Fibrinogen and Platelet Forces in a Cohort of Severely Injured Emergency Department Trauma Patients.

INTRODUCTION: Anticoagulation, fibrinogen consumption, fibrinolytic activation, and platelet dysfunction all interact to produce different clot formation responses after trauma. However, the relative contributions of these coagulation components to overall clot formation remain poorly defined. We examined for sources of heterogeneity in clot formation responses after trauma. METHODS: Blood was sampled in the emergency department from patients meeting trauma team activation criteria at an urban trauma center. Plasma prothrombin time of 18 s or longer was used to define traumatic coagulopathy. Mean kaolin-activated thrombelastography (TEG) parameters were calculated and tested for heterogeneity using analysis of means. Discriminant analysis and forward stepwise variable selection with linear regression were used to determine if prothrombin time, fibrinogen, platelet contractile force (PCF), and D-dimer concentration, representing key mechanistic components of coagulopathy, each contribute to heterogeneous TEG responses after trauma. RESULTS: Of 95 subjects, 16% met criteria for coagulopathy. Coagulopathic subjects were more severely injured with greater shock and received more blood products in the first 8 h compared with noncoagulopathic subjects. Mean (SD) TEG maximal amplitude (MA) was significantly decreased in the coagulopathic group (57.5 [SD, 4.7] mm vs. 62.7 [SD, 4.7], t test P < 0.001). The MA also exceeded the ANOM predicted upper decision limit for the noncoagulopathic group and the lower decision limit for the coagulopathic group at α = 0.05, suggesting significant heterogeneity from the overall cohort mean. Fibrinogen and PCF best discriminated TEG MA using discriminant analysis. Fibrinogen, PCF, and D-dimer were primary covariates for TEG MA using regression analysis. CONCLUSIONS: Heterogeneity in TEG-based clot formation in emergency department trauma patients was linked to changes in MA. Individual parameters representing fibrin polymerization, PCFs, and fibrinolysis were primarily associated with TEG MA after trauma and should be the focus of early hemostatic therapies.