Implications of excessive fibrinolysis and alpha(2)-plasmin inhibitor deficiency in patients with severe head injury

Abstract

Objective: To evaluate the involvement of the fibrinolytic system, especially focused on alpha(2)-plasmin inhibitor, in patients with head injury.

Methods: This study consisted of 47 patients with isolated blunt head trauma in whom blood sampling could be initiated within 3 hours after injury. Patients were divided into two groups according to Glasgow Outcome Scale score status at 3 months after injury. In Group 1 patients (n = 26), the outcome was characterized as good recovery or moderate disability; in Group 2 patients (n = 21), the outcome was characterized as severe disability, vegetative state, or death.

Results: Concentrations of thrombin-antithrombin III complex were greater than 100 microg/L in 39 of 47 patients, and concentrations in Group 2 patients were elevated significantly beyond the concentrations in Group 1 patients. Activities of alpha(2)-plasmin inhibitor in Group 2 were significantly lower than in Group 1 (P < 0.0001). In Group 1 patients, alpha(2)-plasmin inhibitor activity was greater than 60%, while in all but four Group 2 patients, the inhibitor was reduced to less than 60% of normal activity within 3 hours of injury. All patients with alpha(2)-plasmin inhibitor activity less than 60% showed a marked bleeding tendency and/or severe brain edema. Using sandwich enzyme-linked immunosorbent assay, fibrinogen degradation product and fibrin degradation product were measured separately. A significant correlation was apparent between thrombin-antithrombin III complex and fibrinogen degradation product, as well as between the complex and fibrin degradation product. Marked decreases in alpha(2)-plasmin inhibitor were noted only in patients with thrombin-antithrombin III complex concentrations exceeding 500 microg/L.

Conclusion: Fibrinolysis and fibrinogenolysis may be involved according to the degree of coagulation activation in the pathophysiology of severe head injury. Decreased activity of alpha(2)-plasmin inhibitor indicated poor prognosis and may be an exacerbating factor in the acute phase of head trauma.