Fibrinolytic shut-down after surgery: impairment of the balance between tissue-type plasminogen activator and its specific inhibitor.
In nine patients with non-malignant diseases undergoing major upper abdominal surgery, the mechanism of the postoperative fibrinolytic shut-down 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 shut-down of t-PA activity. However, DDAVP infusion was associated with potentially unfavourable increases in the Factor VIII/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.
D000328:Adult; D000368:Aged; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015849:Plasminogen Inactivators; D011183:Postoperative Complications / Q000097:blood*; D010959:Tissue Plasminogen Activator / Q000097:blood*; D014841:von Willebrand Factor / Q000378:metabolism
D006023:Glycoproteins; D015849:Plasminogen Inactivators; D014841:von Willebrand Factor; D005169:Factor VIII; D010959:Tissue Plasminogen Activator; D003894:Deamino Arginine Vasopressin