To the Editor:—
We read with great interest the report of Shore-Lesserson and Reich1regarding a fatal case of venous thromboembolism during cardiac surgery with hypothermic circulatory arrest associated with the use of aprotinin in a patient diagnosed, with postmortem analysis, as a carrier of factor V Leiden. The same authors had previously described two fatal cases of intraoperative thrombosis in patients undergoing the same surgical procedure and treated with ϵ-aminocaproic acid: One of the two patients was a postmortem-diagnosed carrier of the factor V Leiden mutation.2Because of the occurrence over a 3-yr period of four fatal thrombotic events in cardiovascular patients operated on with hypothermic circulatory arrest and treated with antifibrinolytic drugs, the authors of these reports are now screening for the factor V Leiden mutation all patients scheduled to undergo elective surgical procedures requiring hypothermic circulatory arrest to avoid the use of antifibrinolytic drugs in patients who are carriers of the mutation.
It has been proposed to classify the major hereditary prothrombotic conditions in two major groups, including hereditary deficiencies of natural anticoagulants and hereditary disorders associated with increased function of coagulation factors.3The factor V Leiden mutation, which renders activated factor V resistant to proteolysis by activated protein C, belongs to the second group of inherited prothrombotic conditions and is frequently observed in white but not in Asian or African people.4Whereas many subjects with deficiency of natural anticoagulants experience venous thromboembolism before the age of 60 yr, only a minority of factor V Leiden carriers will ever develop thromboembolic events.3If factor V Leiden plays a contributory role in the development of intraoperative thrombosis in patients undergoing cardiac surgery with hypothermic circulatory arrest and receiving antifibrinolytic drugs, then patients with deficiency of natural anticoagulants should be at even greater risk, also given the effect of hemodilution. In addition, screening for the prothrombin G20210A mutation should also be recommended, because the associated hyperprothrombinemia has been shown to inhibit plasma fibrinolysis through a thrombin activatable fibrinolysis inhibitor–mediated mechanism.5On a cost–benefit basis, screening of the general population for thrombophilia defects is ineffective, and it is currently a matter of debate whether such screening should be performed even in patients with venous thromboembolic events.6In the absence of evidence-based data, caution against screening for factor V Leiden patients undergoing cardiovascular surgery with hypothermic circulatory arrest has already been suggested.7Before depriving patients at high risk for bleeding of the proven antihemorrhagic effect of antifibrinolytic drugs,8–10we suggest the institution of an international registry of severe thrombotic complications occurring during cardiac surgery to study the prevalence and the possible causes of this surely underestimated phenomenon. If thrombophilia plays an important role, one would expect history of thromboembolism to be associated with an increased occurrence of this devastating complication of cardiac surgery.
*Policlinico di Monza, Monza, Italy. valter.casati@policlinicodimonza.it