Thrombin Generation in Trauma Patients: How Do we Navigate Through Scylla and Charybdis?

Abstract

Purpose of Review Coagulopathy is a complex pathological condition manifested through the insufficient or excessive tendency to form blood thrombi, which can be caused by trauma and surgery. A promising strategy to mitigate coagulopathy is the balanced restoration of the generation of thrombin — the main enzyme in the blood-coagulation system. We review studies focusing on thrombin, traumatic coagulopathy, and hemostatic balance — a concept aimed to avoid abnormally weak or excessively strong coagulation responses. Recent Findings Thrombin generation is impacted by coagulopathic conditions described by complex patterns, possibly depending on various factors. New methodologies of thrombin-generation measurement and analysis are emerging. Combinations of pro- and anticoagulant proteins can restore thrombin generation in coagulopathy. Balanced therapeutic strategies to improve thrombin generation may lead to favorable clinical outcomes. Summary Thrombin generation is an essential target of pharmacological intervention in traumatic and surgical coagulopathy. Graphic Abstract

Factor VIII: A Dynamic Modulator of Hemostasis and Thrombosis in Trauma

“…Major trauma patients often suffer from both bleeding and thrombotic complications, and balancing the 2 remains a challenging task for clinicians. 77 In a complex trauma resuscitation, clinicians often resort to a protocolized intervention (eg, ratio-based blood component transfusion), but current monitoring strategies are suboptimal in evaluating the efficacy of such interventions in real-time. For example, room-temperature stored platelets may increase circulating platelet counts, but the efficacy of platelet transfusion on hemostasis and clinical outcomes remains questionable.…”

Semi-automated thrombin dynamics applying the ST Genesia thrombin generation assay

“…Moreover, as the TD method partially relies on the computational modeling of the inactivation of thrombin, in silico experimentation can be used to predict the effect of changes in prothrombin conversion and thrombin inactivation on the TG curve. In silico modeling was used in several clinical settings, for example to study the effect of prothrombin complex concentrate administration with and without added antithrombin (AT) after cardiopulmonary bypass surgery ( 17 ), to predict the effect of AT expression targeting in hemophilia patients and investigate inter-patients variability ( 24 ), and in trauma patients ( 25 ).…”