Enhanced fibrinolytic activity during cardiopulmonary bypass in open‐heart surgery in man is caused by extrinsic (tissue‐type) plasminogen activator

Abstract

The nature of the enhanced blood fibrinolytic activity which is known to occur during cardiopulmonary bypass is not understood. We show here that the cause is an increase in extrinsic (tissue-type) plasminogen activator. In six patients, the nature of the enhanced blood fibrinolytic activity that evolved during cardiopulmonary bypass was characterized by differential inhibition using the fibrin plate method and was shown to be C1-inactivator-resistant (extrinsic-activator activity). The C1-inactivator-resistant-activator activity was completely quenched by an antibody against extrinsic (tissue-type) plasminogen activator but not by antiurokinase, proving that the activity was due to the presence of extrinsic (tissue-type) plasminogen activator. The concentration of extrinsic (tissue-type) plasminogen activator increased during cardiopulmonary bypass and disappeared rapidly thereafter. Fibrinogen, plasminogen and alpha 2-antiplasmin were not consumed during cardiopulmonary bypass, while no increase or occasionally a moderate one in fibrinogen degradation products occurred. This is in accord with the property of extrinsic (tissue-type) plasminogen activator which activates plasminogen predominantly at sites where fibrin is present and not in the free circulation.

Centrifugal and roller pumps — are there differences in coagulation and fibrinolysis during and after cardiopulmonary bypass?

“…Previous reports have described an elevation of tPA during CPB [22]. That could also lead to enhanced fibrinolysis without previous thrombin generation.…”

“…However, out results indicate a significant increase of PAP preceding the rise in thrombin generation in the roller pump group, while there was no elevation in the centrifugal pump group. Since anticoagulation in both groups was performed and controlled identically it seems unlikely that insufficient heparinization could have led to enhanced protein C activation by thrombin during CPB [22]. Several mechanisms can be suggested as the reason for out observation in group 1.…”

Usefulness of Intraoperative Continuous Infusion of Tranexamic Acid during Emergency Surgery for Type A Acute Aortic Dissection

“…2) The increase in tissue-PA release begins immediately after the initiation of extracorporeal circulation, and subsequently, the production of plasmin increases more than 100 fold. 3) The blood concentration of PAI-1, which is a primary endogenous tissue-PA antagonist mainly synthesized in the liver, does not increase during extracorporeal circulation.…”

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“…To an organism triggered by extracorporeal circulation, one of the most important reactions is the systemic or generalized inflammatory response, formerly known as "post-perfusion syndrome", "post-cardiotomy syndrome", "homologous blood syndrome", or "pump lung". The term "systemic inflammatory response syndrome" (SIRS) has been proposed to describe the entry point of a spectrum that overlaps with normal postoperative physiology, a subject that has been studied in depth by Kirklin and several other authors [2][3][4][5].…”