The time course of alpha 2-plasmin inhibitor and plasmin-alpha 2-plasmin inhibitor complex levels in patients with traumatic brain injury

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BACKGROUND: In its acute phase, traumatic brain injury (TBI) is notable for disturbances in the coagulation/fibrinolysis system. Plasmin, alpha 2-plasmin inhibitor (α2-PI), and their complex (plasmin-α2-PI complex [PIC]) are important components of the coagulation-fibrinolytic system, but their time courses in the acute phase of TBI and their association with long-term prognosis are unknown. METHODS: We conducted a retrospective analysis of 84 consecutive patients with isolated TBI, during which plasma α2-PI and PIC levels were measured at the time of arrival, as well as at 3, 6, and 12 h, and on days 1, 3, and 7 post-injury. Differences in plasma α2-PI and PIC levels between the good outcome group (extended Glasgow Outcome Scale [GOS-E] of 5-8 at 6 months post-injury) and the poor outcome group (GOS-E of 1-4 at 6 months post-injury) were analyzed using a generalized linear mixed model (GLMM). The hematoma volume of the initial CT scan upon admission and the follow-up CT scan was evaluated using CT volumetry, and then the relationship between changes in hematoma volume and plasma levels of α2-PI and PIC at admission was examined. RESULTS: Abnormally high plasma PIC levels were observed at admission in 97.6% of the patients. In the GLMM adjusted for covariates, the poor outcome group had significantly lower plasma α2-PI activity from admission to 3 days post-injury and significantly higher plasma PIC levels from admission to 6 h post-injury compared to the good outcome group. A negative correlation was found between α2-PI activity at admission and changes in hematoma volume (Spearman's correlation coefficient, r = - 0.587, p = 0.001). CONCLUSIONS: These findings suggest that plasmin was activated and fibrinolysis enhanced immediately after injury in most patients, while in a subset of patients, hematoma expansion due to the suppression of fibrinolytic inhibition by α2-PI negatively affected the outcome.

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