We appreciate the comments presented by Dr. Donahue regarding our report of two cases of fatal aortic thrombosis in association with synthetic antifibrinolytic therapy and deep hypothermic circulatory arrest. We agree that prospective large-scale association studies are necessary in order to make recommendations regarding genetic risk factors and the expenditure of healthcare dollars. The purpose of our report was not to definitively identify any causative agents or conditions in these thrombotic events, but merely to highlight their occurrence in a population of patients that is potentially at higher risk. Certainly, it would not be feasible to recommend that all asymptomatic patients scheduled to undergo cardiac surgery undergo genetic testing for a mutation in the expression of factor V. However, it behooves us as practitioners to be vigilant in our preoperative assessment of patients who may have a personal or a family history of hypercoagulability. This is true because even asymptomatic carriers of the factor V Leiden mutation have an appreciable incidence of thromboembolism that increases when risk factors for thrombosis are present. 1 

The use of antifibrinolytic therapy and the consumptive coagulopathy seen in cardiac surgical patients make this population quite distinct from orthopedic surgical patients or cardiovascular medicine patients in whom factor V Leiden has not been associated with increased thrombosis risk. Prophylactic antifibrinolytic therapy is given with impunity to hundreds of thousands of patients per year who undergo cardiac surgery. 2The use of these drugs has been of apparent benefit to blood conservation practices, but a careful risk-benefit analysis should be performed in light of the question of a small but worrisome possibility that fatal hypercoagulability may be associated with antifibrinolytic therapy.

Since the publication of our case report, we have cared for a patient who experienced fatal intraoperative venous  thrombosis in association with aprotinin therapy and deep hypothermia during valve replacement surgery. While the analysis of this case is ongoing, the initial investigation has shown that the patient's son carries the factor V Leiden mutation.

Though causality should not be inferred from our small anecdotal experience, these types of associations are important in forming the basis for future population-based studies. Finally, the prudent clinician should carefully consider the relative risks and benefits of antifibrinolytic therapy in cardiac surgical patients with known hypercoagulable conditions, such as the factor V Leiden mutation.

Simioni P, Tormene D, Prandoni P, Zerbinati P, Gavasso S, Cefalo P, Girolami A: Incidence of venous thromboembolism in asymptomatic family members who are carriers of factor V Leiden: A prospective cohort study. Blood 2002; 99: 1938–42
Fergusson D, Blair A, Henry D, Hisashige A, Huet C, Koopman-van Gemert A, Katz E, McClelland B, Sigmund H, Laupacis A: Technologies to minimize blood transfusion in cardiac and orthopedic surgery: Results of a practice variation survey in nine countries. International Study of Peri-operative Transfusion (ISPOT) Investigators. Int J Technol Assess Health Care 1999; 15: 717–28