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

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Author: D'Angelo, A. · Kluft, C. · Verheijen, J.H.
Institution: Gaubius Instituut TNO
Source:European Journal of Clinical Investigation, 6, 15, 308-312
Identifier: 229925
Keywords: Biology · blood clotting factor 8 · plasminogen activator inhibitor · blood and hemopoietic system · blood clotting disorder · clinical article · diagnosis · etiology · peripheral vascular system · postoperative thrombosis · Adult · Aged · Desmopressin · Factor VIII · Female · Fibrinolysis · Glycoproteins · Human · Male · Middle Age · Plasminogen Inactivators · Postoperative Complications · Support, Non-U.S. Gov't · Tissue Plasminogen Activator · von Willebrand Factor


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. Chemicals/CAS: blood clotting factor 8, 9001-27-8; desmopressin, 16679-58-6; plasminogen activator inhibitor, 105844-41-5; tissue plasminogen activator, 105913-11-9; Desmopressin, 16679-58-6; Factor VIII, 9001-27-8; Glycoproteins; Plasminogen Inactivators; Tissue Plasminogen Activator, EC; von Willebrand Factor