Early coagulopathy after traumatic brain injury: The role of hypoperfusion and the protein C pathway

Introduction: Early coagulopathy after traumatic brain injury (TBI) is thought to be the result of injury-mediated local release of tissue factor, although the precise mechanisms that cause hypoperfusion and early systemic coagulopathy in TBI patients are unknown. We have previously reported that early systemic coagulopathy after trauma is present only when tissue injury is associated with severe hypoperfusion leading to the activation of the protein C pathway. However, the role of hypoperfusion as an important mechanism for the development of coagulopathy early after TBI is unclear. The objective of the present study was to determine the importance of hypoperfusion and protein C activation in causing early coagulopathy in TBI patients. Materials: We performed a prospective cohort study including patients with isolated brain injury admitted to a single trauma center. Blood was drawn on aver-age 32 minutes after injury. Plasma samples were assayed for protein C and thrombomodulin by standard laboratory techniques. Routine coagulation measures (prothrombin time, partial tbromboplastin time) and arterial blood gas analysis were performed concurrently. Severe hypoperfusion was evidenced by the presence of an arterial base deficit greater than 6. Results: Thirty-nine TBI patients were included in the study during a 15month period. TBI patients without concurrent hypoperfusion (n = 28) did not develop an early coagulopathy after trauma, no matter the severity of injury. In contrast, patients with TBI who also had severe hypoperfusion (BD >6) (n = 11) were coagulopathic early after injury. Indeed, these patients had higher prothrombin time and partial thromboplastin time, compared with those with TBI and a BD <6 (17.6 +/- 3.6 vs. 14.3 +/- 2.3, p < 0.005; and 43.13 +/- 18.3 vs. 27.4 +/- 3.8, p < 0.0001). Unactivated protein C levels were lower in the TBI group with BD >6 (56 +/- 32 vs. 85 +/- 35, p = 0.03) and thrombomodulin levels were significantly higher (48 +/- 26 vs. 35 +/- 10, p = 0.04). Without hypoperfusion, there was no effect of increasing brain injury on protein C pathway or fibrinolysis pathway mediators. Conclusions: TBI alone does not cause early coagulopathy, but must be coupled with hypoperfusion to lead to coagulation derangements, associated with the activation of the protein C pathway. This novel finding has significant implications for the treatment of coagulopathy after severe brain injury.