Abstract :
Background. The endothelium plays a pivotal role in the regulation of anticoagulant and procoagulant pathways and imbalance can produce disturbances in coagulation. Serine protease inhibitors are also important controllers of the coagulation system. Aprotinin can reduce postoperative bleeding, although the mechanism of action is not clearly defined. This article focuses on a study in children with congenital heart disease scheduled for cardiac operations to determine the influence of aprotinin on plasmatic or endothelial-related natural inhibitors.
Methods. Thirty children were randomly allocated either to an aprotinin-treated group or to a control group. Levels of thrombomodulin, protein C, free protein S, and thrombin/antithrombin complex were measured before, during, and after cardiopulmonary bypass until the first postoperative day.
Results. Levels of antithrombin III, protein C and protein S, and fibrinogen, platelet count, and activated partial thromboplastin time were without differences between the two groups. Thrombin/antithrombin plasma concentrations increased significantly during cardiopulmonary bypass, without showing any differences between aprotinin-treated and nontreated children. Thrombomodulin plasma concentrations during cardiopulmonary bypass and until 5 hours after cardiopulmonary bypass were significantly lower in the aprotinin-treated children than in the control group. By the first postoperative day, the levels in the aprotinin-treated patients had returned to baseline.
Conclusions. The results suggest a direct or indirect effect of aprotinin on endothelial cell thrombomodulin expression and release in a soluble form into the circulation. Whether the lower plasma concentrations with aprotinin are related to suppression of proinflammatory mediators and preservation of endothelial cell function or whether aprotinin has a direct action on thrombomodulin expression by the endothelium can only be speculated.
