Coagulation Factor V (Arg⁵⁰⁶ → Gln) Mutation and Early Saphenous Vein Graft Occlusion after Coronary Artery Bypass Grafting

Summary

The factor V (Arg⁵⁰⁶→Gln) mutation confers an increased risk of deep vein thrombosis, whereas its role in saphenous vein graft closure after coronary artery bypass grafting (CABG) remains unclear. This study examined the anticoagulant response to activated protein C (APC ratio) in relation to the surgical trauma and the significance of the factor V Leiden mutation in determining postoperative thrombin generation and fibrin formation and the risk of early vein graft occlusion. A total of 108 men undergoing elective CABG for exertional angina pectoris (mean age 61.1 ± 8.7 years) were examined. The patency of saphenous vein grafts was studied at routine reangiography three months after CABG.

Of 100 patients who underwent reangiography, 23 had one or more occluded vein grafts at reangiography. Heterozygosity for the factor V (Arg⁵⁰⁶→Gln) mutation tended to be associated with early saphenous vein graft occlusion (5/11 carriers vs. 18/89 non-carriers with graft occlusion, व² = 3.52, p = 0.06), whereas pre- and postoperative APC ratios did not. Pre- and postoperative determinations of prothrombin fragment 1+2, thrombin-antithrombin complexes and soluble fibrin levels did not differ between patients with and without the mutation.

Early saphenous vein graft occlusion after CABG could tentatively be added to deep vein thrombosis as a vascular complication that can be attributed to the factor V (Arg⁵⁰⁶→Gln) mutation.

• References

• 1 Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C.. Nature 1994; 369: 64-67.
• 2 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: Prediction of a cofactor to activated protein C.. Proc Natl Acad Sci USA 1993; 90: 1004-8.
• 3 Griffin JH, Evatt BL, Wideman C, Fernandez JA. Anticoagulant protein C pathway defective in a majority of thrombophilic patients.. Blood 1993; 82: 1989-93.
• 4 Koster T, Rosendaal FR, de Ronde F, Brïet E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor response to activated protein C: Leiden thrombophilia study.. Lancet 1993; 342: 1503-6.
• 5 Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis.. N Engl J Med 1994; 330: 517-21.
• 6 Cox JL, Chiasson DA, Gotlieb AI. Stranger in a strange land: The pathogenesis of saphenous vein graft stenosis with emphasis on structural and functional differences between veins and arteries.. Progr Cardiovasc Dis 1991; 34: 45-68.
• 7 Verstraete M, Brown BG, Chesebro JH, Ekeström S, Harker LA, Hender son AH, Jewitt DE, Oliver MF, Sleight P. Evaluation of antiplatelet agents in the prevention of aorto-coronary bypass occlusion.. Eur Heart J 1986; 7: 4-13.
• 8 Pfisterer M, Jockers G, Regenass S. et al. Trial of low-dose aspirin plus dipyridamole versus anticoagulants for prevention of aortocoronary vein graft occlusion.. Lancet 1989; 2: 1-7.
• 9 Vermylen C, de Vreker RA, Verstraete M. A rapid enzymatic method for assay of fibrinogen fibrin polymerisation time (FPT test).. Clin Chim Acta 1963; 8: 418-24.
• 10 Morrissey JH, Macik BG, Neuenschwander PF, Comp PC. Quantitation of activated factor VII levels in plasma using a tissue factor mutant selectively deficient in promoting factor VII activation.. Blood 1993; 81: 734-44.
• 11 Silveira A, Green F, Karpe F, Blombäck M, Humphries S, Hamsten A. Elevated levels of factor VII activity in the postprandial state: effect of the factor VII Arg-Gln polymorphism.. Thromb Haemost 1994; 72: 734-9.
• 12 Pelzer H, Schwarz A, Heimburger N. Determination of human ThrombinAntithrombin III complex in plasma with an enzyme-linked immunosor-bent assay.. Thromb Haemost 1988; 59: 101-6.
• 13 Pelzer H, Schwarz A, Stuber W. Determination of human prothrombin fragment 1+2 in plasma with an antibody against a synthetic peptide.. Thromb Haemost 1991; 65: 153-9.
• 14 Malm J, Laurell M, Dahlbäck B. Changes in the plasma levels of vitamin K-dependent proteins C and S and of C4b-binding protein during pregnancy and oral contraception.. Br J Haematol 1988; 68: 437-43.
• 15 Chmielewska J, Wiman B. Determination of tissue plasminogen activator and its “fast” inhibitor in plasma.. Clin Chem 1986; 32 (03) 482-5.
• 16 Ødegaard OR, Try K, Andersson TR. Protein C: An automated activity assay.. Haemostasis 1987; 17: 109-13.
• 17 Wiman B, Rånby M. Determination of soluble fibrin in plasma by rapid and quantitative spectrophotometric assay.. Thromb Haemost 1986; 55: 189-93.
• 18 Carlson K. Lipoprotein fractionation.. J Clin Path 1973; 5 (Suppl. 026) 32-7.
• 19 Arnesen H, Semb G, Hol R, Karlsen H. Fibrinolytic capacity after venous stasis in patients undergoing aorto-coronary by-pass surgery. Relation to shunt occlusion.. Scand J Haematol 1983; 30 (Suppl. 39) 43-6.
• 20 Eritsland J, Gjønnes G, Sandset PM, Seljeflot I, Arnesen H. Activated protein C resistance and graft occlusion after coronary artery bypass surgery.. Thromb Res 1995; 79: 223-6.
• 21 Rosén S, Johansson K, Lindberg K, Dahlbäck B. (for the APC resistance group). Multicenter evaluation of a kit for activated protein C resistance on various coagulation instruments using plasmas from healthy individuals.. Thromb Haemost 1994; 72: 255-60.
• 22 Freyburger G, Bilhou-Nabera C, Dief S, Javorschi S, Labrouche S, Lerebeller MJ, Boisseau MR. Technical and biological conditions influencing the functional APC resistance test.. Thromb Haemost 1996; 75: 460-5.
• 23 Alhenc-Gelas M, Gandrille S, Aubry ML, Emmerich J, Fiessinger JN, Aiach M. Unexplained thrombosis and factor V Leiden mutation.. Lancet 1994; 344: 555-6.
• 24 Zöller B, Holm J, Svensson P, Dahlbäck B. Elevated levels of prothrombin activation fragment 1+2 in plasma from patients with heterozygous Arg⁵⁰⁶ to Gln mutation in the factor V gene (APC-resistance) and/or inherited protein S deficiency.. Thromb Haemost 1996; 75: 270-4.
• 25 Martinelli I, Bottasso B, Duca F, Faioni E, Mannuccio Mannucci P. Heightened thrombin generation in individuals with resistance to activated protein C.. Thromb Haemost 1996; 75: 703-5.
• 26 Holm J, Zöller B, Svensson PJ, Berntorp E, Erhardt L, Dahlbäck B. Myo cardial infarction associated with homozygous resistance to activated protein C.. Lancet 1994; 344: 952-3.
• 27 März W, Seydewitz H, Winkelmann B, Chen M, Nauck M. Mutation in coagulation factor V associated with resistance to activated protein C in patients with coronary artery disease.. Lancet 995 345: 526-7.
• 28 Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke and venous thrombosis in apparently healthy men.. N Engl J Med 1995; 332: 912-7.
• 29 Kontula K, Ylikorkala A, Miettinen H, Vuorio A, Kauppinen-Mäkelin R, Hämäläinen L, Palomäki H, Kaste M. Arg 506Gln factor V mutation (factor V Leiden) in patients with ischemic cerebrovascular disease and survivors of myocardial infarction.. Thromb Haemost 1995; 73: 558-60.
• 30 Prohaska W, Mannebach H, Schmidt M, Gleichmann U, Kleesiek K. Evidence against heterozygous coagulation factor V 1691 G→A mutation with resistance to activated protein C being a risk factor for coronary artery disease and myocardial infarction.. Mol Med 1995; 73: 521-4.
• 31 Demarmels Biasiutti F, Merlo C, Furlan M, Sulzer I, Binder BR, Lämmle B. No association of APC resistance with myocardial infarction.. Blood Coag Fibrinol 1995; 6: 456-9.
• 32 Holm J, Zöller B, Berntorp E, Erhardt L, Dahlbäck B. Prevalence of factor V gene mutation amongst myocardial infarction patients and healthy controls is higher in Sweden than in other countries.. J Intern Med 1996; 239: 221-6.
• 33 Ardissino D, Peyvandi F, Merlini PA, Colombi E, Mannucci PM. Factor V (Arg⁵⁰⁶→Gln) mutation in young survivors of myocardial infarction.. Thromb Haemost 1996; 75: 701-2.