Sensitivity to Activated Protein C; Influence of Oral Contraceptives and Sex

Summary

We investigated sensitivity to activated protein C (APC) in 43 men, 42 women not using oral contraceptives (OC) and 38 women using OC containing 30.0-37.5 μg ethinyl estradiol. A commercially available kit was used. Men were more sensitive to APC as compared with women not using OC (p <0.005), but this difference seems not to be of clinical importance. Women using OC showed to be significantly less sensitive to APC, reflected by a lower APC-ratio, as compared with men (p <0.005) and women not using OC (p <0.05).

So, in normal individuals the APC-sensitivity differs according to sex and estrogen intake. This should be taken into account when interpreting APC-ratios.

• References

• 1 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognised mechanism characterized by poor anticoagulant response to activated protein C: Prediction of a cofactor to activated protein C. Proc Natl Acad Sci 1993; 90: 1004-1008
• 2 Marlar RA, Kleiss AJ, Griffin JH. Mechanism of action of human activated protein C, a thrombin-dependent anticoagulant enzyme. Blood 1982; 59 (05) 1067-1072
• 3 Walker FJ. Protein S and the regulation of activated protein C. Sem Thromb Haemost 1984; 10 (02) 131-138
• 4 Broekmans AW, Veltkamp JJ, Bertina RM. Congenital protein C deficiency and venous thromboembolism. A study of three dutch families N Engl J Med 1983; 309: 340-344
• 5 Comp PC, Nixon RR, Cooper R, Esmon CT. Familial protein S deficiency is associated with recurrent thrombosis. J Clin Invest 1984; 74: 2082-2088
• 6 Rogers GM, Chandler WL. Laboratory and clinical aspects of inherited thrombotic disorders. Am J Hematol 1992; 41: 113-122
• 7 Griffin JH, Evatt B, Wideman C, Fernández JA. Anticoagulant protein C pathway defective in majority of thrombophilie patients. Blood 1993; 82 (07) 1989-1993
• 8 Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330 (08) 517-522
• 9 Koster T, Rosendaal FR, de Ronde H, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden thrombophilia study. Lancet 1993; 342: 1503-1506
• 10 Dahlbäck B, Hildebrand B. Inherited resistance to activated protein C is corrected by anticoagulant cofactor activity found to be a property of factor V. Proc Natl Acad Sci 1994; 91: 1396-1400
• 11 Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velde PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-67
• 12 Greengard JS, Sun X, Xu S, Fernandez JA, Griffin JH, Evatt B. Activated protein C resistance caused by Arg50-6Gln mutation in factor V a. Lancet 1994; 343: 1361-1362
• 13 Voorberg J, Roelse J, Koopman R, Büller H, Berends F, ten Cate JW, Mertens C, van Mourik JA. Association of idiopathic venous thromboembolism with single point-mutation at Arg⁵⁰⁶of factor V. Lancet 1994; 343: 1535-1536
• 14 Zöller B, Dahlbäck B. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet 1994; 343: 1536-1538
• 15 Beller FK, Ebert C. Effects of oral contraceptives on blood coagulation. A Review Obstet Gynecol Surv 1985; 40: 425-436
• 16 Bonnar J. Coagulation effects of oral contraceptives. Am J Obstet Gynecol 1987; 157: 1042-1048
• 17 Daume E. Influence of modern low-dose oral contraceptives on hemostasis. Adv Contracep 1990; 6 Suppl 51-68
• 18 Boerger LM, Morris PC, Thurnau GR, Esmon CT, Comp PC. Oral contraceptives and gender affect protein S status. Blood 1987; 69 (02) 692-694
• 19 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: 437-443
• 20 Rosén S, Johansson K, Lindberg K, Dahlbäck B. Multicenter evaluation of a kit for activated protein C resistance on various coagulation instruments using plasmas from healthy individuals. Thromb Haemost 1994; 72 (02) 255-260