CHARACTERIZATION OF PROTHROMBIN ACTIVATION DURING CARDIAC-SURGERY BY HEMOSTATIC MOLECULAR MARKERS

Background: Prothrombin activation represents the key regulatory step in the hemostatic process. Once formed, thrombin contributes to the ge neration of fibrin as well as the activation of platelets and fibrinol ysis. Failure to suppress thrombin formation during cardiac surgery co uld result in disorders of hemostasis and thrombosis in the perioperat ive period. The aim of this study was to determine the time course for prothrombin activation during the perioperative period associated wit h cardiac surgery. Methods: We measured prothrombin activation during the perioperative period in 19 adult patients undergoing primary cardi ac surgery using enzyme-linked immunosorbent assays for the detection of thrombin formation (prothrombin fragment 1.2 and thrombin-antithrom bin III complex) and thrombin activity (fibrinopeptide A and fibrin mo nomer). Blood samples were obtained preoperatively; at 30-min interval s during cardiopulmonary bypass (CPB); and 1, 3, and 20 h after comple tion of CPB. Results: Despite anticoagulation with heparin, plasma con centrations of prothrombin fragment 1.2, thrombin-antithrombin III com plex, and fibrin monomer increased throughout CPB. Peak concentrations for all hemostatic markers occurred in the samples obtained 3 h after completion of CPB. By the morning after surgery, plasma prothrombin f ragment 1.2 returned to preoperative concentrations; however, fibrinop eptide A and fibrin monomer concentrations remained significantly incr eased (P < 0.05) compared to preoperative values. Conclusions: These d ata clearly demonstrate the occurrence of prothrombin activation and t hrombin activity during CPB despite heparin concentrations adequate to maintain the activated clotting time greater than 400 s. Hemostatic m arkers for the activation of prothrombin demonstrated peak concentrati ons 3 h after completion of CPB with a return to baseline concentratio ns by the morning after surgery. Markers for thrombin activity, howeve r, suggest the presence of active thrombin through the morning after s urgery. Further investigations will be necessary to determine the role of hemostatic activation in thrombotic complications after cardiac su rgery.