Early hemostatic responses to trauma identified with hierarchical clustering analysis

Abstract

Background Trauma-induced coagulopathy is a complex multifactorial hemostatic response that is poorly understood. Objectives Identify distinct hemostatic responses to trauma and identify key components of the hemostatic system that vary between responses. Patients/Methods Cross-sectional observational study of adult trauma patients at an urban Level I trauma center Emergency Department. Hierarchical clustering analysis was used to identify distinct clusters of similar subjects using vital signs, injury/shock severity, and by comprehensive assessment of coagulation, clot formation, platelet function, and thrombin generation. Results Of 84 total trauma patients included in the model, three distinct trauma clusters were identified. Cluster 1 (N=57) displayed platelet activation, preserved peak thrombin generation, plasma coagulation dysfunction, moderately decreased fibrinogen concentration, and normal clot formation relative to healthy controls. Cluster 2 (N=18) displayed platelet activation, preserved peak thrombin generation, and preserved fibrinogen concentration with normal clot formation. Cluster 3 (N=9) was the most severely injured and shocked and displayed a strong inflammatory and bleeding phenotype. Platelet dysfunction, thrombin inhibition, plasma coagulation dysfunction, and decreased fibrinogen concentration were present in this cluster. Fibrinolytic activation was present in all clusters, but increased more so in Cluster 3. Trauma clusters were different most noticeably in their relative fibrinogen concentration, peak thrombin generation, and platelet-induced clot contraction. Conclusions Hierarchical clustering analysis identified 3 distinct hemostatic responses to trauma. Further insight into the underlying hemostatic mechanisms responsible for these responses is needed.

Acute Fibrinolysis Shutdown after Injury Occurs Frequently and Increases Mortality: A Multicenter Evaluation of 2,540 Severely Injured Patients

“…Original work on trauma-induced coagulopathy hypothesized that both tissue injury and shock were necessary for driving this process (24), which appeared to be validated in an animal model(25). However, with the emergence of unique phenotypes of TIC(26) in the context that alteration in clot formation does not correlate with alteration in clot degradation (3, 4), implications of coagulation abnormalities beyond protein C is evident.…”

Multiple organ dysfunction after trauma

“…The calibration and goodness of fit of the logistic regression models were evaluated using the χ 2 Hosmer-Lemeshow (HL) test, and model discrimination was assessed by means of area under the receiver operating characteristic curve (AUROC). Correlations Duration of critical care stay (days)* 3 (2-5) 7 (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) 20 (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) 36 (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47) 11 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)…”

Response to Letter to the Editor submitted by Dr. Wada and Dr. Yamakawa re: Trauma‐induced coagulopathy: The past, present, and future

“…[10][11][12] Furthermore, it should be noted that the addition of thrombomodulin in thrombin generation assays can prolong the lag time and decrease the peak and endogenous-thrombin potential, 13,14 which may regulated by cell surfaces rather than enzymatic protein and protease reactions and consumptive pathologies alone, and the robust data generated by independent groups of investigators using hierarchical clustering analyses to identify heterogeneity in phenotypes of clot formation and lysis in trauma populations. [20][21][22] Specifically, these clustering analyses have confirmed that not all phenotypes of TIC can be explained by clotting factor changes or solely mediated by thrombin.…”