Protamine enhances fibrinolysis by decreasing clot strength: role of tissue factor-initiated thrombin generation

The Annals of Thoracic Surgery
Vance G Nielsen

Abstract

Excessive protamine administration to neutralize heparin after cardiopulmonary bypass has been implicated as a cause of postoperative hemorrhage. Protamine directly inhibits thrombin and tissue factor (TF)-mediated activation of factor VII. However, the half-life of protamine is only 4.5 minutes; thus the purpose of this study was to determine if protamine could enhance fibrinolysis, explaining the delayed, protamine-associated hemorrhage observed in the postoperative period. Human plasma containing 0, 6.25, 12.5, or 25 microg/mL of protamine (n = 6 per condition) was exposed to 0.01% tissue factor and tissue-type plasminogen activator (tPA, 100 U/mL) for 30 minutes, with clot growth and disintegration measured by Thromboelastograph (Haemoscope Corp, Skokie, IL). The TF was increased to 0.1% in additional experiments with plasma containing protamine (25 microg/mL) and tPA. Protamine significantly (p < 0.05) delayed the time to clot initiation, decreased the speed of clot propagation, and diminished clot strength in a concentration-dependent fashion. The onset of fibrinolysis was significantly (p < 0.05) increased only in samples with 25 microg/mL of protamine, and the rate of clot lysis was not different among the conditions. T...Continue Reading

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Citations

May 2, 2009·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Ravi TanejaJohn Murkin
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Dec 21, 2006·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Vance G NielsenBrad L Steenwyk
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Dec 21, 2006·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Vance G Nielsen, Truitt C Ellis
May 13, 2008·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Vance G Nielsen
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