title: Aprotinin reduces blood loss after cardiopulmonary bypass by direct inhibition of plasmin.
abstract: The effectiveness and mechanism of aprotinin reduced bleeding after cardiopulmonary bypass surgery was studied in a double blind randomised study of 106 patients undergoing valve replacement surgery. Aprotinin therapy was associated with significant reduction in perioperative bleeding and postoperative blood transfusion requirements. Although initially tissue plasminogen activator (t-PA) activity was lower in the aprotinin than placebo group, as surgery proceeded this difference was reversed due to less plasminogen activator inhibitor-1 release in the aprotinin group. This indicates that aprotinin-mediated suppression of fibrinolysis as demonstrated by reduced D-dimer concentration was not related to t-PA. Furthermore, similar perioperative reduction of plasminogen levels in aprotinin and placebo groups indicated a similar degree of conversion of plasminogen to plasmin. However, less plasmin bound with alpha 2-antiplasmin in the plasma in the aprotinin group as it was already complexed with aprotinin where it remained protected from the natural inhibitor on the intact fibrin surface. The reduced fibrinolytic activity of the aprotinin group was thus brought about by the complexing of aprotinin with the plasmin which was bound to the fibrin surface.
authors.affiliation: Department of Haematology, The Prince Charles Hospital, Brisbane, Australia. mjray@bit.net.au
authors.forename: M J
authors.initials: MJ
authors.lastname: Ray
authors.forename: N A
authors.initials: NA
authors.lastname: Marsh
mesh_terms: D000328:Adult; D007611:Aprotinin / Q000627:therapeutic use*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005341:Fibrinolysin / Q000037:antagonists & inhibitors*; D005342:Fibrinolysis; D006438:Hemodilution; D006801:Humans; D019106:Postoperative Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D013917:Thrombin / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D015842:Serine Proteinase Inhibitors; C036309:fibrin fragment D; D007611:Aprotinin; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin