Clotting and fibrinolytic disturbance during lung transplantation: Effect of low-dose aprotinin

Abstract

Patients undergoing lung transplantation are often confronted with a bleeding problem that may be due in part to the use of cardiopulmonary bypass and its activation of blood clotting and fibrinolysis. Objective: We performed a prospective study to determine whether and to what extent the clotting and fibrinolytic systems are being activated and whether low-dose aprotinin is effective in inhibiting blood activation during lung transplantation. Methods: Thirty lung transplantations performed on 29 patients were divided into a group with cardiopulmonary bypass alone ( n = 12), a group with cardiopulmonary bypass and 2 × 10 6 KIU aprotinin administered at the beginning of bypass in the pump prime ( n = 12), and a group without cardiopulmonary bypass ( n = 6). Serial blood samples were taken from the recipient before anesthesia, seven times during the operation, and 4 and 24 hours thereafter. Results: Results show that in the group having cardiopulmonary bypass alone, the concentration of the clotting marker thrombin/antithrombin III complex increased significantly during the early phase of the operation ( p < 0.01) and remained high until the end of the operation. Levels of tissue-type plasminogen activator, a trigger of fibrinolysis released by injured endothelium, also increased sharply in the early phase of the operation in the cardiopulmonary bypass group ( p < 0.01), followed by a significant increase in fibrin degradation products ( p < 0.01). In the aprotinin group, a significant reduction of thrombin/antithrombin III complex ( p < 0.05), tissue-type plasminogen activator ( p < 0.05), and fibrin degradation products ( p < 0.05) was observed in the early phase of the operation compared with levels in the bypass group, but these markers increased late during bypass associated with a significant drop ( p < 0.05) of plasma aprotinin level monitored by plasmin inhibiting capacity. In the nonbypass group, concentrations of thrombin/antithrombin III complex and tissue-type plasminogen activator also rose significantly ( p < 0.05) in the early phase of the operation, but the levels were significantly lower than those of the bypass group ( p < 0.05). Blood loss during the operation was 2521 ± 550 ml in the bypass group, 1991 ± 408 ml in the aprotinin/bypass group, and 875 ± 248 ml in the nonbypass group. Conclusion: These results suggest that clotting and fibrinolysis are activated during lung transplantation, especially in patients undergoing cardiopulmonary bypass. Aprotinin in a low dose significantly reduced activation of clotting and fibrinolysis in the early phase of the operation but not during the late phase of lung transplantation. (J T HORAC C ARDIOVASC S URG 1996;112:599-606)