(Circulation. 1997;96:569-574.)
© 1997 American Heart Association, Inc.
Articles |
Aprotinin Inhibits Plasmin-Induced Platelet Activation During Cardiopulmonary Bypass
From the Division of Cardiovascular Surgery (O.S., T.J., Y.T., N.A., Y.S., T.M.) and the Division of Hematology (H.K., T.N.), Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Correspondence to Dr Osamu Shigeta, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305, Japan.
Background In the past few years, aprotinin has been used in cardiac surgery with impressive results of reducing blood loss, but several adverse effects of aprotinin also have been reported. One of the most likely mechanisms is the inhibition of plasmin by aprotinin, although this indirect effect has not been reproduced in all experimental studies.
Methods and Results We evaluated the platelet function
and fibrinolytic activity during human cardiac surgery, with or without
aprotinin. During cardiopulmonary bypass (CPB) in humans
without aprotinin (n=16), decrease of platelet aggregation induced
by thrombin, increase of 
-granule secretion of platelet and
microparticle formation, and increase of
plasmin/2-antiplasmin complex (PIC) were observed. In
contrast, low-dose aprotinin (1.0x106 KIU), which was
administered only into the priming fluid of extracorporeal circuits
(n=10), maintained platelet aggregation induced by thrombin and
reduced -granule secretion and microparticle formation of
platelets during CPB. In vitro, plasmin (0.8 CU/mL) released
-granules of washed platelets, and this activation was
completely inhibited by aprotinin (10 KIU/mL).
Conclusions Aprotinin has indirect effects to inhibit platelet activation, and this may partly explain the reduction of blood loss during cardiac surgery. To prevent the adverse effects, a single and minimal use of aprotinin is important. The results of in vivo and in vitro studies suggest that platelet preservation was demonstrated by the lower concentration of aprotinin (1.0x106 KIU per patient or 10 KIU/mL) compared with the concentration that inhibits plasma fibrinolysis.
Key Words: platelets • cardiopulmonary bypass • surgery • fibrinolysis
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