Fibrinolytic shut‐down after surgery: impairment of the balance between tissue‐type plasminogen activator and its specific inhibitor

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Abstract
In nine patients with non‐malignant diseases undergoing major upper abdominal surgery, the mechanism of the postoperative fibrinolytic shutdown was investigated because of its potential significance for postoperative deep vein thrombosis by employing new and specific methods for assessing and stimulating the fibrinolytic system. The shut‐down was found to result from an impairment of the balance between tissue‐type plasminogen activator, t‐PA, and its recently discovered fast‐acting inhibitor. In this balance, the t‐PA antigen concentrations both in resting conditions and after stimulation evoked by desamino‐d‐arginine vasopressin (DDAVP) were found to be unchanged by surgery. However, there was a significant postoperative increase in t‐PA inhibitor levels. The release of t‐PA under the stimulus of DDAVP infusion overcame the postoperative shutdown of t‐PA activity. However, DDAVP infusion was associated with potentially unfavourable increases in the Factor VHI/von Willebrand factor complex. The discovery of increased t‐PA inhibitor in the postoperative period opens new possibilities for a rational approach to reduce or abolish the postoperative fibrinolytic shut‐down.