Aprotinin reduces cardiopulmonary bypass-induced blood loss and inhibits fibrinolysis without influencing platelets.
Cardiopulmonary bypass (CPB) induces a bleeding defect which leads to enhanced blood loss. A double-blind study was carried out comparing aprotinin with placebo in patients undergoing re-operation for heart valve replacement. The results confirm that aprotinin is effective at reducing such loss. In the placebo treated group, significant increases were observed, during CPB, in the plasma concentrations of fibrinolytic activity, tissue plasminogen activator antigen, D-dimer, and beta-thromboglobulin. Platelet counts fell within 5-10 min of the patients going onto CPB, but this could be accounted for by the dilutional effect of the extracorporeal circuit. Inhibition of responsiveness of platelets, as judged by aggregometry, was significant only at the end of bypass when collagen was the agonist and after protamine reversal when ristocetin was the agonist. CPB did not enhance the release, into the circulation, of glycocalicin (a proteolytic fragment of glycoprotein Ib). In the aprotinin-treated group, the formation of fibrin degradation products as measured by D-dimer was inhibited. However, aprotinin did not influence the change in platelet count, suppress beta-thromboglobulin release from platelets, prevent the inhibition of platelet function or influence the concentration of plasma glycocalicin during the study period. These observations confirm that CPB leads to a fibrinolytic state and less responsive platelets. This study also indicates that aprotinin-induced reduction in blood loss is associated with inhibition of plasmin-mediated fibrin digestion and that the mechanism by which aprotinin reduces blood loss is not via protection of platelets during CPB.
Orchard
M A
MA
Department of Clinical Medicine, University of Leeds, U.K.
Goodchild
C S
CS
Prentice
C R
CR
Davies
J A
JA
Benoit
S E
SE
Creighton-Kemsford
L J
LJ
Gaffney
P J
PJ
Michelson
A D
AD
D000328:Adult; D000368:Aged; D000933:Antifibrinolytic Agents / Q000097:blood; D000990:Antithrombin III / Q000187:drug effects; D007611:Aprotinin / Q000627:therapeutic use*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D001792:Blood Platelets / Q000187:drug effects*; D002315:Cardiopulmonary Bypass; D004311:Double-Blind Method; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000187:drug effects; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000097:blood; D001620:beta-Thromboglobulin / Q000187:drug effects
D000933:Antifibrinolytic Agents; D005338:Fibrin Fibrinogen Degradation Products; C046193:antithrombin III-protease complex; D001620:beta-Thromboglobulin; C036309:fibrin fragment D; D000990:Antithrombin III; D007611:Aprotinin; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator