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J Thorac Cardiovasc Surg 2008;135:487-491
© 2008 The American Association for Thoracic Surgery

Editorial

Aprotinin: Twenty-five years of claim and counterclaim

Oxford Heart Centre, John Radcliffe Hospital, Oxford, United Kingdom

Received for publication January 14, 2008; accepted for publication January 14, 2008.

^_* Address for reprints: Stephen Westaby, BSc, MS, PhD, Oxford Heart Centre, John Radcliffe Hospital, Oxford 0X9 3DU, United Kingdom. (Email: swestaby@ahf.org.uk).

The first 300 words of the full text of this article appear below.

See related articles on pages 495, 573, and 685.

 

The coagulopathy after blood–foreign surface interaction in the cardiopulmonary bypass circuit is part of the "postperfusion syndrome," which historically has accounted for as many deaths as has cardiac insufficiency. Cardiopulmonary bypass induces platelet dysfunction, thrombin production, and plasmin release.¹ These changes provide the basis for postoperative hemorrhage, cardiac tamponade, and the need for surgical re-entry or excessive blood transfusion. Antiplatelet therapy in patients with coronary artery disease further compounded these effects. In turn, transfusion of packed red blood cells and coagulation components is recognized to increase the risk of morbidity and mortality after cardiac surgery.^2,3

An Important Discovery

In the early 1980s, the Kirklin group in Alabama began to pursue the pathophysiologic mechanisms underlying the postperfusion syndrome. In short, blood–foreign surface interaction and protamine administration were both found to activate complement. Complement anaphylatoxins caused neutrophil activation, intrapulmonary white cell sequestration, and release of protease enzymes and free radicals. Twenty-five years ago at the Hammersmith Hospital, my colleagues and I sought to attenuate the inflammatory response by using the only commercially available protease inhibitor, aprotinin, which had been used unsuccessfully to treat pancreatitis. At this stage, no interaction was known or anticipated between aprotinin and the coagulation system. The hemostatic mechanism was discovered when the surgical field was noted to be abnormally dry after cardiopulmonary bypass. As the therapeutic potential became apparent, guidelines for aprotinin use were developed by trial and error. Using the standard celite–activated clotting time (ACT) of greater than 450 seconds for heparin monitoring, blood often set solid in the pericardium with a shiny glazed appearance. Intraoperative events such as spontaneous vein graft thrombosis or clotting within the oxygenator were not uncommon until it was recognized that aprotinin alone prolonged the celite ACT and the in vitro activated partial thromboplastin time.⁴ This . . . [Full Text of this Article]

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				D. Royston Aprotinin; An economy of truth? J. Thorac. Cardiovasc. Surg., September 1, 2008; 136(3): 798 - 799. [Full Text] [PDF]