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

Abstract

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 remains 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 (PT) ≥ 18 sec was used to define traumatic coagulopathy. Mean kaolin-activated thrombelastography (TEG) parameters were calculated and tested for heterogeneity using Analysis of Means (ANOM). Discriminant analysis and forward stepwise variable selection with linear regression were used to determine if PT, 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 hours compared to non-coagulopathic subjects. Mean (SD) TEG maximal amplitude (MA) was significantly decreased in the coagulopathic group=57.5 (4.7) mm, vs. 62.7 (4.7), T test p<0.001. The MA also exceeded the ANOM predicted upper decision limit for the non-coagulopathic group and the lower decision limit for the coagulopathic group at alpha=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. Conclusion Heterogeneity in TEG-based clot formation in Emergency Department trauma patients was linked to changes in MA. Individual parameters representing fibrin polymerization, platelet contractile forces, and fibrinolysis were primarily associated with TEG MA after trauma and should be the focus of early hemostatic therapies.

Post-translational oxidative modification of fibrinogen is associated with coagulopathy after traumatic injury

“…The earliest documented change in clot formation in trauma patients is a reduction of clot strength or elastic modulus when measured using viscoelastic methods [3, 42]. Our previous work suggests a similar reduction in elastic and storage modulus of fibrin clot when fibrinogen was exposed to HOCl in vitro [15].…”

The use of viscoelastic haemostatic assays in the management of major bleeding

“…Viscoelastic haemostatic assays measures which are used to diagnose trauma coagulopathy vary but can be broadly summarised by three main changes: prolongation of clot formation, reduction in clot strength and increase in fibrinolysis. The most common abnormalities include: reduction in A and MCF (ROTEM) (Tauber et al , ; Wooley et al , ; Meyer et al , ) and reduction in MA (TEG) (Meyer et al , ; White et al , ) – all measures of clot strength, and low clot strength is viewed as an important marker, suggesting higher bleeding risk. However, no consensus value is yet agreed – for example Davenport et al () used an EXTEM A5 of ≤35 mm as diagnostic of trauma coagulopathy whereas Hagemo et al () used ≤40 mm.…”

Onset of Coagulation Function Recovery Is Delayed in Severely Injured Trauma Patients with Venous Thromboembolism

“…Several studies have indicated that fibrinogen acts as a compensatory mechanism for platelet dysfunction and coagulopathy following severe injury. 13, 20–22 In turn, this could also enhance VTE risk in our patient population. Fibrinogen significantly contributes to clot strength, ranging from 23% in healthy individuals 9, 10 to over 40% in trauma patients.…”