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

• Published in: European journal of clinical investigation Vol. 15; no. 6; p. 308
• Main Authors: D'Angelo, A, Kluft, C, Verheijen, J H, Rijken, D C, Mozzi, E, Mannucci, P M
• Format: Journal Article
• Language: English
• Published: England 01.12.1985
• Subjects: Adult; Aged; Deamino Arginine Vasopressin - pharmacology; Factor VIII - metabolism; Female; Fibrinolysis - drug effects; Glycoproteins - blood; Humans; Male; Middle Aged; Plasminogen Inactivators; Postoperative Complications - blood; Tissue Plasminogen Activator - blood; von Willebrand Factor - metabolism
• ISSN: 0014-2972
• DOI: 10.1111/j.1365-2362.1985.tb00277.x

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.