Thrombin formation

Abstract

Thrombin plays a central role in hemorrhage control. In this chapter, we outline the key features of the response to vascular damage from a thrombin-centric perspective. Following vascular injury, cell and cell-derived microparticle membranes support the enzymatic reactions that lead to thrombin formation and fibrin deposition. Prothrombin activation to thrombin is sequential, and its cleavage may preferentially yield the active anticoagulant enzyme meizothrombin under certain conditions. Thrombin generation is dysregulated in traumatic injury, contributing to coagulopathic extremes of uncontrolled bleeding or excessive clotting. Mechanisms that impair thrombin generation in trauma include hemodilution, hypothermia, and acidosis. In contrast, circulating microparticles and histones promote thrombin generation. Measurement of the kinetics of thrombin generation during the course of resuscitation may improve the diagnosis and management of trauma-induced coagulopathy.