Free
Correspondence  |   April 2007
Thrombosis after Hypothermic Circulatory Arrest for Cardiovascular Surgery, Antifibrinolytic Drugs, and Thrombophilia
Author Affiliations & Notes
  • Valter Casati, M.D.
    *
  • *Policlinico di Monza, Monza, Italy.
Article Information
Correspondence
Correspondence   |   April 2007
Thrombosis after Hypothermic Circulatory Arrest for Cardiovascular Surgery, Antifibrinolytic Drugs, and Thrombophilia
Anesthesiology 4 2007, Vol.106, 874. doi:10.1097/01.anes.0000264780.84360.06
Anesthesiology 4 2007, Vol.106, 874. doi:10.1097/01.anes.0000264780.84360.06
To the Editor:—
We read with great interest the report of Shore-Lesserson and Reich1 regarding 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.2 Because 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.3 The 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.4 Whereas 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.3 If 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.5 On 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.6 In 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.7 Before depriving patients at high risk for bleeding of the proven antihemorrhagic effect of antifibrinolytic drugs,8–10 we 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.
References
Shore-Lesserson L, Reich DL: A case of severe diffuse venous thromboembolism associated with aprotinin and hypothermic circulatory arrest in a cardiac surgical patient with factor V Leiden. Anesthesiology 2006; 105:219–21Shore-Lesserson, L Reich, DL
Fanashawe MP, Shore-Lesserson L, Reich DL: Two cases of fatal thrombosis after aminocaproic acid therapy and deep hypothermic circulatory arrest. Anesthesiology 2001; 95:1525–7Fanashawe, MP Shore-Lesserson, L Reich, DL
Crowther MA, Kelton JG: Congenital thrombophilic states associated with venous thrombosis: A qualitative overview and proposed classification system. Ann Intern Med 2003; 138:128–34Crowther, MA Kelton, JG
Ridker PM, Miletich JP, Hennekens CH, Buring JE: Ethnic distribution of factor V Leiden in 4047 men and women: Implication for venous thromboembolism screening. JAMA 1997; 277:1305–7Ridker, PM Miletich, JP Hennekens, CH Buring, JE
Colucci M, Binetti BM, Tripodi A, Chantarangkul V, Semeraro N: Hyperprothrombinemia associated with prothrombin G20210A mutation inhibits plasma fibrinolysis through a TAFI-mediated mechanism. Blood 2004; 103:2157–61Colucci, M Binetti, BM Tripodi, A Chantarangkul, V Semeraro, N
Baglin T, Luddington R, Brown K, Baglin C: Incidence of recurrence venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet 2003; 362:523–6Baglin, T Luddington, R Brown, K Baglin, C
Donahue BS: Thrombosis after deep hypothermic circulatory arrest with antifibrinolytic therapy: Is factor V Leiden the smoking gun? Anesthesiology 2002; 97:760–1Donahue, BS
Dumont E, Carrier M, Cartier R, Pellerin M, Poirier N, Bouchard D, Perrault LP: Repair of aortic false aneurysm using deep hypothermia and circulatory arrest. Ann Thorac Surg 2004; 78:117–21Dumont, E Carrier, M Cartier, R Pellerin, M Poirier, N Bouchard, D Perrault, LP
Tweddell JS, Hoffman GM, Mussatto KA, Fedderly RT, Berger S, Jaquiss RD, Ghanayem NS, Frisbee SJ, Litwin SB: Improved survival of patients undergoing palliation of hypoplastic left heart syndrome: lessons learned from 115 consecutive patients. Circulation 2002; 106 (suppl 1):I82–9Tweddell, JS Hoffman, GM Mussatto, KA Fedderly, RT Berger, S Jaquiss, RD Ghanayem, NS Frisbee, SJ Litwin, SB
Casati V, Sandrelli L, Speziali G, Calori G, Grasso MA, Spagnolo S: Hemostatic effects of tranexamic acid in elective thoracic aortic surgery: A prospective, randomized, double-blind, placebo-controlled study. J Thorac Cardiovasc Surg 2002; 123:1084–91Casati, V Sandrelli, L Speziali, G Calori, G Grasso, MA Spagnolo, S