Antifibrinolytic Therapy and Pulmonary Thromboembolism During Orthotopic Liver Transplantation

Abstract

In Response: We appreciate the interest expressed by Parker and Irefin in our recent publication. Regarding Case 1, they felt that our “empiric” use of aprotinin during orthotopic liver transplantation (OLT) was unjustified without documentation of a preexisting coagulopathy or evidence of ongoing fibrinolysis because of the potential for thrombotic complications. However, while we agree that monitoring of fibrinolysis is important during OLT, previous data have demonstrated the utility of prophylactic aprotinin therapy during OLT, presumably because of the underlying hemostatic abnormalities that characterize patients with end-stage liver disease and the propensity for fibrinolysis after allograft reperfusion (1–5). Although the efficacy of aprotinin in this setting is admittedly controversial, serious thrombotic complications were not observed in any of the published trials. Our approach in this case was thus consistent with the existing literature regarding aprotinin use during OLT. Additionally, Parker and Irefin also question the use of prophylactic ε-aminocaproic acid use during OLT as described in Case 2, again citing the potential for thrombotic complications. However, ε-aminocaproic acid is frequently used during OLT (6,7) and a review of the prevailing literature failed to reveal any significant thrombotic complications. Despite this paucity of data regarding the prothrombotic risk of antifibrinolytic drug use during OLT, we agree that aprotinin, together with other ill-defined factors favoring thrombosis, may increase the risk of serious thromboembolic events. This was the intended message of our report. Parker and Irefin note the possible etiologic role of the presumed clot in the right internal jugular vein. We did, however, pointedly acknowledge and discuss the potential role of this preoperative abnormality. They finally suggest that low flows during veno-venous bypass (VVB) may have precipitated fibrin deposition in the bypass circuit, which then migrated to the right heart. Although we cannot exclude activation of clotting within the VVB circuit, flows were always greater than 2 L/min before the hypotensive and hypoxemic event. After the onset of hemodynamic instability, the flows decreased, but the perfusion staff promptly and appropriately discontinued the VVB pump. The temporal sequence of events and the transesophageal echocardiographic findings strongly support the view that the low VVB flows were secondary to the massive pulmonary thromboembolism rather than a primary etiologic factor in its formation. We appreciate the insightful comments of Parker and Irefin regarding the role of coagulation monitoring during OLT as a guide to blood product replacement and the selective use of antifibrinolytic agents. Nonetheless, it remains our judgment that aprotinin use was justified on the basis of the known coagulation and fibrinolytic abnormalities characteristic of similar patients undergoing OLT (especially reoperative procedures) (1–5), the absence of documented or widely accepted serious thrombotic risks associated with aprotinin, the presence of data supporting its beneficial impact on fibrinolysis and transfusion requirements (1–5), and because of the ongoing clinical evidence of impaired hemostasis. In hindsight, we believe the similarity of these two events, the rarity of pulmonary embolism during OLT, and the reports of four other identical events associated with aprotinin use during OLT, all suggest a possible prothrombotic effect of aprotinin in certain patients undergoing OLT. Thus, it may be prudent to avoid aprotinin during OLT in the absence of demonstrable clinical or laboratory evidence of fibrinolysis because of the potential risk of life-threatening thromboembolic events. Christopher J. O’Connor MD Kenneth J. Tuman MD