Coagulopathy by Hypothermia and Acidosis: Mechanisms of Thrombin Generation and Fibrinogen Availability

Background: Although the lethal triad of hypothermia, acidosis, and coagulopathy has been recognized for a decade, the underlying mechanisms related to the development of coagulopathy are not fully understood. Consequently, current strategy in treating trauma patients with coagulopathy is limited to "Staying out of the trouble" instead of "getting out of trouble." A better understanding of the underlying mechanisms will facilitate the search for effective therapeutic approaches when this lethal triad cannot be avoided. Methods: Reviewing recent studies that explored alterations of thrombin generation and fibrinogen availability caused by hypothermia and acidosis. Results: Hypothermia and acidosis compromise thrombin-generation kinetics via different mechanisms. Hypothermia primarily inhibits the initiation phase, whereas acidosis severely inhibits the propagation phase of thrombin generation. Similarly, hypothermia and acidosis affect fibrinogen metabolism differently. Hypothermia inhibits fibrinogen synthesis, whereas acidosis accelerates fibrinogen degradation, leading to a potential deficit in fibrinogen availability. In addition, coagulation complications caused by acidosis cannot be immediately corrected by pH neutralization alone. Conclusions: Hypothermia and acidosis impair thrombin generation and fibrinogen availability via different mechanisms. Current data indicate that pH correction alone cannot immediately correct acidosis-induced coagulation impairments. Future studies are warranted to test the effects of pH neutralization in conjunction with fibrinogen supplementation in normalizing acidosis-induced clotting complications.