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

Abstract

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.

Keywords: Alpha-2-antiplasmin; Blood coagulation disorders; Fibrinolysis; Prognosis; Traumatic brain injury.

Fig. 1

A head CT scan of a 79-year-old female with traumatic brain injury. The left two columns show the initial CT scan upon admission (A), while the right two columns display the follow-up CT scan taken 120 min later (B). On each side, the left shows the original CT scan, and the right shows the CT scan with the hematoma highlighted in red. Acute subdural hematoma, cerebral contusion, and traumatic subarachnoid hemorrhage were observed, with successful segmentation of the hematoma regions based on attenuation values above a certain threshold. No misclassification of bone or calcification was observed. In this case, the hematoma volume on the initial CT scan was 30.1 mL, while the hematoma volume on the follow-up CT scan was 59.6 mL

Fig. 2

Boxplots showing plasma levels of alpha 2-plasmin inhibitor (α2-PI) of all patients on admission and 3 h, 6 h, 12 h, 1 day, 3 days, and 7 days after traumatic brain injury. ***p < 0.001, N.S = Not Significant

Fig. 3

Boxplots showing plasma levels of plasmin-alpha 2-plasmin inhibitor complex (PIC) of all patients on admission and 3 h, 6 h, 12 h, 1 day, 3 days, and 7 days after traumatic brain injury. ***p < 0.001, N.S = Not Significant

Fig. 4

Line graph showing plasma levels of alpha 2-plasmin inhibitor (α2-PI) of cases with good outcome and poor outcome on admission and 3 h, 6 h, 12 h, 1 day, 3 days, and 7 days after traumatic brain injury. Plasma α2-PI activities were significantly lower in the poor outcome group than in the good outcome group from the time of admission to 3 days post-injury, in the analysis using a generalized linear mixed model incorporating age, Glasgow Coma Scale score, presence of acute subdural hematoma, and surgical intervention as covariates. ***p < 0.001, N.S = Not Significant

Fig. 5

Line graph showing plasma levels of plasmin-alpha 2-plasmin inhibitor complex (PIC) of cases with a good outcome and poor outcome on admission and 3 h, 6 h, 12 h, 1 day, 3 days, and 7 days after traumatic brain injury. Plasma levels of PIC were significantly higher in the poor outcome group than in the good outcome group from the time of admission to 6 h post-injury, in the analysis using a generalized linear mixed model incorporating age, Glasgow Coma Scale score, presence of acute subdural hematoma, and surgical intervention as covariates. *p < 0.05, **p < 0.01, N.S = Not Significant

Fig. 6

Relationship between plasma alpha 2-plasmin inhibitor (α2-PI) activity at admission and changes in hematoma volume of the initial computed tomography (CT) scan upon admission and the follow-up CT scan. A negative correlation was observed between α2-PI activity at admission and the change in hematoma volume (Spearman’s correlation coefficient, r =  − 0.587, p = 0.001)