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Ann Thorac Surg 1998;66:373-381
© 1998 The Society of Thoracic Surgeons

Original articles: cardiovascular

Integrilin prevents prolonged bleeding times after cardiopulmonary bypass1

Yasuyuki Suzuki, MDa,b,c, Priscilla Hillyer, BSEa,b,c, Shinji Miyamoto, MDa,b,c, Stefan Niewiarowski, MD, PhDa,b,c, Ling Sun, MDa,b,c, A. Koneti Rao, MDa,b,c, Stanley Hollenbach, BSa,b,c, L. Henry Edmunds, Jr, MDa,b,c

a Harrison Surgical Research Laboratories, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
b Sol Sherry Thrombosis Research Center, Department of Medicine, Temple University, Philadelphia, Pennsylvania, USA
c COR Therapeutics Inc, San Francisco, CA, USA

Address reprint requests to Dr Edmunds, Department of Surgery, Hospital of University of Pennsylvania, 6 Silverstein, 3400 Spruce St, Philadelphia, PA 19104-4283
e-mail: (hedmunds{at}mail.med.upenn.edu)

Presented at the Thirty-fourth Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 26, 1998.

Background. Cardiopulmonary bypass reduces platelet number and function, increases postoperative bleeding time, and is the major, unsolved cause of nonsurgical bleeding after open heart operations. Temporary inhibition of platelet function during cardiopulmonary bypass (platelet anesthesia) protects platelets and reduces postoperative bleeding time and bleeding.

Methods. Integrilin, a short-acting, reversible platelet glycoprotein IIb/IIIa inhibitor was studied in 28 baboons that had 60 minutes of normothermic cardiopulmonary bypass using peripheral cannulas. A control group, two groups that received different doses of Integrilin, and a group that received a combination of Integrilin and low-dose Iloprost were studied. Blood samples for platelet count, aggregation to adenosine diphosphate, ß-thromboglobulin, prothrombin fragment F1.2, thrombin-antithrombin complex, and fibrinopeptide A were obtained at seven time points. Template bleeding times were measured before and at five intervals after cardiopulmonary bypass.

Results. Both doses of Integrilin and the combination of Integrilin and Iloprost significantly protected platelet number, inhibited the response to adenosine diphosphate, and reduced postoperative bleeding times, but they did not reduce ß-thromboglobulin release except in the high-dose Integrilin group. Thrombin formation and activity were qualitatively, but not significantly, reduced in all treatment groups. Bleeding times were not significantly different from baseline at the time protamine was given in the combination group and 60 minutes after protamine administration in all treatment groups.

Conclusions. Integrilin alone or in combination with Iloprost significantly reduces platelet activation during cardiopulmonary bypass and produces normal or near-normal bleeding times at the time protamine is given.




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