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

Background. Aprotinin reduces perioperative bleeding after open heart surge ry, primarily by inhibiting fibrinolysis. In addition, the drug has both pr ocoagulant and anticoagulant effects that involve complex reactions of coag ulation proteins and cells that are incompletely understood. This study tes ts the hypothesis that aprotinin has an anticoagulant effect on the extrins ic coagulation pathway. Methods. Human heparinized blood was recirculated through a membrane oxygen ator with and without high concentrations of aprotinin (18.4 mu M). Serial plasma samples were obtained at intervals up to 240 minutes. Results. Aprotinin significantly reduced the progressive increase in prothr ombin fragments (F1.2) and thrombin-antithrombin complex beginning immediat ely. Aprotinin also significantly reduced monocyte expression of tissue fac tor 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 p athway. Later, aprotinin inhibits monocyte expression of tissue factor and the extrinsic coagulation pathway. The ability of aprotinin to inhibit mono cyte tissue factor provides a means to reduce thrombin formation in blood a spirated from the wound during open heart surgery. (C) 1999 by The Society of Thoracic Surgeons.