Role of excessive fibrinolysis in patients with severe head injury

Shigeki Kushimoto, Yasushi Shibata, Yukio Ikeda, Shinsuke Ishino, Hidetaka Sato, Yasuo Murai, Kazuyoshi Ohashi, Yasuhiro Yamamoto

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Introduction: Abnormalities in the coagulation and fibrinolytic system can be developed in patients with severe head injuries. The brain tissue contains high concentration of tissue factor, which activates extrinsic coagulation pathway after head injuries, subsequently produces hypercoagulable state followed by fibrinolytic activation. It has been reported that the degree of abnormalities in the coagulation and fibrinolysis can be an independent predictor of outcome. Based on these observations, we evaluated the importance of fibrinolytic activities in the pathogenesis of severe head injury, especially focused on α2-plasmin inhibitor (α2-PI). Materials and Methods: Thirteen consecutive patients admitted with isolated head injury to our department within 2 hrs after injury were studied. Patients with clinical and laboratory evidence for hepatic impairment were excluded. A Glasgow Coma Scale of ≤8 points was 8 cases, ≥9 was 5. Seven of 13 patients died. Blood samples were collected on admission and serially, coagulation and fibrinolytic parameters were measured. Results: In all patients, abnormalities of coagulation and fibrinolysis were evident on admission. All patients showed markedly elevated concentration of thrombin-antithrombin III complex, which were ≥100 μg/L. Although plasma levels of FDP, D-dimer, and plasmin-α2-PI complex were increased in non-survivors as compared to survivors (248.4 ± 264.3 vs 68.0 ± 58.7 μg/mL, p <0.05 ;143.8 ± 156.3 vs 43.8 ± 31.3 μg/mL, ns ;22.7 ± 23.4 vs 12.8 ± 10.1 μg/mL, ns. respectively), the levels of these parameters showed large deviations. Plasma α2-PI levels of non-survivors were 55% or less on admission, while more than 60% in survivors (46.3 ± 13.2 vs 78.0 ± 10.2%, p <0.001). In non-survivors, delayed intracerebral hemorrhage or marked bleeding tendency during surgery were shown. Conclusion: α2-PI is the most important inhibitor of fibrinolysis, and it has been reported that excessive fibrinolysis and plasmin-induced endothelial injury occur in its deficiency. The results suggest that excessive fibrinolysis induced by secondary α2-PI deficiency may contribute to the pathophysiology of severe head injury.

Original languageEnglish
Pages (from-to)A78
JournalCritical Care Medicine
Issue number1 SUPPL.
Publication statusPublished - 1999


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