Abstract
In severe trauma, excessive fibrinolytic activation is associated with an increase in the transfusion volume and mortality rate. However, in the first several hours after a blunt trauma, changes in fibrinolytic activation, suppression, and activation–suppression balance have not yet been elucidated, which the present study aimed to clarify. Anesthetized 9-week-old male Wistar S/T rats experienced severe blunt trauma while being placed inside the Noble–Collip drum. Rats were randomly divided into four groups of seven. The no-trauma group was not exposed to any trauma; the remaining groups were analysed 0, 60, and 180 min after trauma. Immediately following trauma, total tissue-plasminogen activator (tPA) levels significantly increased in the plasma, and the balance of active tPA and active plasminogen activator inhibitor-1 (PAI-1) significantly tipped toward fibrinolytic activation. After trauma, both tPA and PAI-1 levels increased gradually in various organs and active and total PAI-1 levels increased exponentially in the plasma. Total plasma tPA levels 60 min after trauma returned quickly to levels comparable to those in the no-trauma group. In conclusion, fibrinolytic activation was observed only immediately following trauma. Therefore, immediately after trauma, the fibrinolytic system was activated; however, its activation was quickly and intensely suppressed.
Highlights
Excessive fibrinolytic activation is associated with an increase in the transfusion volume and mortality rate[1,2,3,4,5]
The released tissueplasminogen activator (tPA) activates plasminogen to plasmin, which degrades fibrinogen and fibrin[10]. This fibrinolytic system is regulated by three distinct inhibitors comprising plasminogen activator inhibitor-1 (PAI-1), α2 plasmin inhibitor (α2PI), and thrombin-activatable fibrinolysis inhibitor (TAFI)[11,12,13]
The active tPA and active PAI-1 ratios significantly increased compared to the ratio before trauma, and the balance between activation and suppression of the fibrinolytic system tipped toward fibrinolytic activation
Summary
Excessive fibrinolytic activation is associated with an increase in the transfusion volume and mortality rate. Following trauma, total tissueplasminogen activator (tPA) levels significantly increased in the plasma, and the balance of active tPA and active plasminogen activator inhibitor-1 (PAI-1) significantly tipped toward fibrinolytic activation. Excessive fibrinolytic activation is associated with an increase in the transfusion volume and mortality rate[1,2,3,4,5]. Many investigations have reported that excessive fibrinolytic activation is observed in patients immediately following severe trauma[3,4,5]. Tissue-plasminogen activator (tPA) may play a central role in excessive fibrinolytic activation immediately following trauma in patients with severe trauma[1,9]. Activation of plasminogen to plasmin by tPA on the fibrin surface strongly reduces[13]
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