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Ann Thorac Surg 1999;68:473-478
© 1999 The Society of Thoracic Surgeons

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Original Articles

Aprotinin inhibits thrombin formation and monocyte tissue factor in simulated cardiopulmonary bypass

^a Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
^b Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA
^c Department of Chemical Engineering, University of Delaware, Newark, Delaware, USA

Address reprint requests to Dr Colman, Sol Sherry Thrombosis Research Center, Temple University School of Medicine, 3400 North Broad St, Philadelphia, PA 19140
e-mail: colmanr{at}astro.temple.edu

Background. Aprotinin reduces perioperative bleeding after open heart surgery, primarily by inhibiting fibrinolysis. In addition, the drug has both procoagulant and anticoagulant effects that involve complex reactions of coagulation proteins and cells that are incompletely understood. This study tests the hypothesis that aprotinin has an anticoagulant effect on the extrinsic coagulation pathway.

Methods. Human heparinized blood was recirculated through a membrane oxygenator with and without high concentrations of aprotinin (18.4 µM). Serial plasma samples were obtained at intervals up to 240 minutes.

Results. Aprotinin significantly reduced the progressive increase in prothrombin fragments (F1.2) and thrombin-antithrombin complex beginning immediately. Aprotinin also significantly reduced monocyte expression of tissue factor and Mac-1. Aprotinin did not significantly reduce factor VII or factor VIIa.

Conclusions. During simulated cardiopulmonary bypass, aprotinin immediately inhibits kallikrein and thrombin formation via the intrinsic coagulation pathway. Later, aprotinin inhibits monocyte expression of tissue factor and the extrinsic coagulation pathway. The ability of aprotinin to inhibit monocyte tissue factor provides a means to reduce thrombin formation in blood aspirated from the wound during open heart surgery.

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