(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
This article has been cited by other articles:
 |
|
 |
|
  D. L. Ngaage, A. R. Cale, M. E. Cowen, S. Griffin, and L. Guvendik Aprotinin in Primary Cardiac Surgery: Operative Outcome of Propensity Score-Matched Study Ann. Thorac. Surg., October 1, 2008; 86(4): 1195 - 1202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Alacacioglu, M. A. Ozcan, O. Piskin, F. Yuksel, A. Alacacioglu, F. Demirkan, H. G. Ozsan, M. Polat, Y. Ozgenc, and B. Undar Increased Concentration of Soluble CD40 Ligand in Preeclampsia Clinical and Applied Thrombosis/Hemostasis, April 1, 2007; 13(2): 201 - 205. [Abstract] [PDF]
|
|
|
|
 |
|
 J. R. S. Day, R. C. Landis, and K. M. Taylor Aprotinin and the protease-activated receptor 1 thrombin receptor: antithrombosis, inflammation, and stroke reduction. Seminars in Cardiothoracic and Vascular Anesthesia, June 1, 2006; 10(2): 132 - 142. [Abstract] [PDF]
|
|
|
|
 |
|
 A. M. Mahdy and N. R. Webster Perioperative systemic haemostatic agents Br. J. Anaesth., December 1, 2004; 93(6): 842 - 858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Chong, C. R. Hampton, and E. D. Verrier Microvascular Inflammatory Response in Cardiac Surgery Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2003; 7(3): 333 - 354. [Abstract] [PDF]
|
|
|
|
|
|
R. C. Landis Aprotinin: Antithrombotic and Vasoactive Mechanisms of Action Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2002; 6(4): 307 - 312. [Abstract] [PDF]
|
|
|
|
 |
|
 L. Burysek, T. Syrovets, and T. Simmet The Serine Protease Plasmin Triggers Expression of MCP-1 and CD40 in Human Primary Monocytes via Activation of p38 MAPK and Janus Kinase (JAK)/STAT Signaling Pathways J. Biol. Chem., August 30, 2002; 277(36): 33509 - 33517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Horigome, Y. Hiramatsu, O. Shigeta, T. Nagasawa, and A. Matsui Overproduction of platelet microparticles in cyanotic congenital heart disease with polycythemia J. Am. Coll. Cardiol., March 20, 2002; 39(6): 1072 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Landis, G. Asimakopoulos, M. Poullis, D. O. Haskard, and K. M. Taylor The antithrombotic and antiinflammatory mechanisms of action of aprotinin Ann. Thorac. Surg., December 1, 2001; 72(6): 2169 - 2175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Samson and L. Shore-Lesserson Platelet Function and Cardiopulmonary Bypass Seminars in Cardiothoracic and Vascular Anesthesia, November 1, 2001; 5(4): 273 - 281. [Abstract] [PDF]
|
|
|
|
|
|
R. C. Landis, D. O. Haskard, and K. M. Taylor New antiinflammatory and platelet-preserving effects of aprotinin Ann. Thorac. Surg., November 1, 2001; 72(5): S1808 - 1813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Hennein Inflammation After Cardiopulmonary Bypass: Therapy for the Postpump Syndrome Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2001; 5(3): 236 - 255. [Abstract] [PDF]
|
|
|
|
 |
|
 K. N. Sturk-Maquelin, R. Nieuwland, and A. Sturk Reply J. Thorac. Cardiovasc. Surg., August 1, 2001; 122(2): 405 - 406. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Syrovets, M. Jendrach, A. Rohwedder, A. Schule, and T. Simmet Plasmin-induced expression of cytokines and tissue factor in human monocytes involves AP-1 and IKK{beta}-mediated NF-{kappa}B activation Blood, June 15, 2001; 97(12): 3941 - 3950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Poullis, R. Manning, M. Laffan, D. O. Haskard, K. M. Taylor, and R. C. Landis The antithrombotic effect of aprotinin: actions mediated via the proteaseactivated receptor 1 J. Thorac. Cardiovasc. Surg., August 1, 2000; 120(2): 370 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K Biswas, L. Lewis, and J. F Sommerauer Aprotinin in the management of life-threatening bleeding during extracorporeal life support Perfusion, May 1, 2000; 15(3): 211 - 216. [Abstract] [PDF]
|
|
|
|
 |
|
 S. A. Kozek-Langenecker, S. F. Mohammad, T. Masaki, C. Kamerath, and A. K. Cheung The Effects of Heparin, Protamine, and Heparinase 1 on Platelets in vitro Using Whole Blood Flow Cytometry Anesth. Analg., April 1, 2000; 90(4): 808 - 812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. O’Connor, D. V. Brown, M. Avramov, S. Barnes, H. N. O’Connor, and K. J. Tuman The Impact of Renal Dysfunction on Aprotinin Pharmacokinetics During Cardiopulmonary Bypass Anesth. Analg., November 1, 1999; 89(5): 1101 - 1101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Weerasinghe and K. M. Taylor The platelet in cardiopulmonary bypass Ann. Thorac. Surg., December 1, 1998; 66(6): 2145 - 2152. [Abstract] [Full Text] [PDF]
|
|