Is APC Resistance a Risk Factor for Venous Thromboembolism in Patients over 70 Years?

Emmanuel Oger; Karine Lacut; Grégoire Le Gal; Patrick Van Dreden; Luc Bressollette; Pierre-Yves Scarabin; Christophe Leroyer; Dominique Mottier

doi:10.1055/s-0037-1613260

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2002; 88(04): 587-591
DOI: 10.1055/s-0037-1613260

Review Article

Schattauer GmbH

Is APC Resistance a Risk Factor for Venous Thromboembolism in Patients over 70 Years?

Emmanuel Oger

¹G. E.T. B. O. (Groupe d’Etude de la Thrombose de Bretagne Occidentale), Department of Internal Medicine and Chest Diseases, Hôpital de la Cavale Blanche, Brest

,

Karine Lacut

¹G. E.T. B. O. (Groupe d’Etude de la Thrombose de Bretagne Occidentale), Department of Internal Medicine and Chest Diseases, Hôpital de la Cavale Blanche, Brest

,

Grégoire Le Gal

¹G. E.T. B. O. (Groupe d’Etude de la Thrombose de Bretagne Occidentale), Department of Internal Medicine and Chest Diseases, Hôpital de la Cavale Blanche, Brest

,

Patrick Van Dreden

²Serbio (Diagnostica Stago), Gennevilliers

,

Luc Bressollette

¹G. E.T. B. O. (Groupe d’Etude de la Thrombose de Bretagne Occidentale), Department of Internal Medicine and Chest Diseases, Hôpital de la Cavale Blanche, Brest

,

Pierre-Yves Scarabin

³INSERM Unit 258, Villejuif, France

,

Christophe Leroyer

¹G. E.T. B. O. (Groupe d’Etude de la Thrombose de Bretagne Occidentale), Department of Internal Medicine and Chest Diseases, Hôpital de la Cavale Blanche, Brest

,

Dominique Mottier

¹G. E.T. B. O. (Groupe d’Etude de la Thrombose de Bretagne Occidentale), Department of Internal Medicine and Chest Diseases, Hôpital de la Cavale Blanche, Brest

› Institutsangaben

Abstract

Summary

Activated protein C (APC) resistance is the most common risk factor for venous thromboembolism (VTE). Previous studies mostly analysed patients under 70 years and reported a four-to sevenfold increased risk. This case-control study included consecutive patients referred for a clinical suspicion VTE to our medical unit: 621 patients with a well-documented diagnosis (cases) and 406 patients for which the diagnosis was ruled out and who had no personal history of VTE (controls). APC resistance related to factor V Leiden was defined by either a positive DNA analysis or a positive STA^® Staclot APC-R assay. Under 70 years, APC resistance was associated with a threefold increased risk of VTE (odds ratio 3.2, 95% CI, 1.7 to 6.0), whereas in patients over 70 years, it appeared to be no longer a strong risk factor (odds ratio 0.8, 95% CI, 0.4 to 1.7). Age appeared as an effectmeasure modifier with a significant interaction (p = 0.005). Our data suggest that APC resistance is not a risk factor for VTE in elderly.

Keywords

APC resistance - venous thrombosis - elderly

Volltext

Referenzen

References
1 Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999; 353: 1167-73.
2 Dahlback B. Resistance to activated protein C as risk factor for thrombosis: molecular mechanisms, laboratory investigation, and clinical management. Semin Hematol 1997; 34: 217-34.
3 Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, De Ronde H. et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
4 Koster T, Rosendaal FR, De Ronde H, Briet E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet 1993; 342: 1503-6.
5 Svensson PJ, Dahlback B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-22.
6 Desmarais S, De Moerloose P, Reber G, Minazio P, Perrier A, Bounameaux H. Resistance to activated protein C in an unselected population of patients with pulmonary embolism. Lancet 1996; 347: 1374-5.
7 Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood 1995; 85: 1504-8.
8 Baglin TP, Brown K, Williamson D, Baker P, Luddington R. Relative risk of pulmonary embolism and deep vein thrombosis in association with the factor V Leiden mutation in a United Kingdom population [letter]. Thromb Haemost 1997; 77: 1219.
9 Leroyer C, Mercier B, Escoffre M, Ferec C, Mottier D. Factor V Leiden prevalence in venous thromboembolism patients. Chest 1997; 111: 1603-6.
10 Martinelli I, Cattaneo M, Panzeri D, Mannucci PM. Low prevalence of factor V: Q506 in 41 patients with isolated pulmonary embolism. Thromb Haemost 1997; 77: 440-3.
11 Ehrenforth S, Zwinge B, Scharrer I. High prevalence of factor V R506Q mutation in German thrombophilic and normal population [letter]. Thromb Haemost 1998; 79: 684-5.
12 Olafsson I, Hjaltadottir S, Onundarson PT, Porarinsdottir R, Haraldsdottir V. Prevalence of factor V(Q506). and prothrombin 20210 A mutations in an apparently healthy Icelandic population and patients suffering from venous thrombosis [letter]. Thromb Haemost 1998; 79: 685-6.
13 Alhenc-Gelas M, Arnaud E, Nicaud V, Aubry ML, Fiessinger JN, Aiach M. et al. Venous thromboembolic disease and the prothrombin, methylene tetrahydrofolate reductase and factor V genes. Thromb Haemost 1999; 81: 506-10.
14 Lindmarker P, Schulman S, Sten-Linder M, Wiman B, Egberg N, Johnsson H. The risk of recurrent venous thromboembolism in carriers and noncarriers of the G1691A allele in the coagulation factor V gene and the G20210A allele in the prothrombin gene. DURAC Trial Study Group. Duration of Anticoagulation. Thromb Haemost 1999; 81: 684-9.
15 Salomon O, Steinberg DM, Zivelin A, Gitel S, Dardik R, Rosenberg N. et al. Single and combined prothrombotic factors in patients with idiopathic venous thromboembolism: prevalence and risk assessment. Arterioscler Thromb Vasc Biol 1999; 19: 511-8.
16 Bjorgell O, Nilsson PE, Nilsson JA, Svensson PJ. Location and extent of deep vein thrombosis in patients with and without FV: R 506Q mutation. Thromb Haemost 2000; 83: 648-51.
17 De Moerloose P, Reber G, Perrier A, Perneger T, Bounameaux H. Prevalence of factor V Leiden and prothrombin G20210A mutations in unselected patients with venous thromboembolism. Br J Haematol 2000; 110: 125-9.
18 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.
19 Rodeghiero F, Tosetto A. Activated protein C resistance and factor V Leiden mutation are independent risk factors for venous thromboembolism. Ann Intern Med 1999; 130: 643-50.
20 Ridker PM, Glynn RJ, Miletich JP, Goldhaber SZ, Stampfer MJ, Hennekens CH. Age-specific incidence rates of venous thromboembolism among heterozygous carriers of factor V Leiden mutation. Ann Intern Med 1997; 126: 528-31.
21 Oger E, Leroyer C, Bressollette L, Nonent M, Le Moigne E, Bizais Y. et al. Evaluation of a new, rapid, and quantitative D-Dimer test in patients with suspected pulmonary embolism. Am J Respir Crit Care Med 1998; 158: 65-70.
22 The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. JAMA 1990; 263: 2753-9.
23 Oger E, Leroyer C, Mercier B, van Dreden P, Bressollette L, Saint-Martin L. et al. Assessment of activated protein C resistance using a new and rapid venom-based test: STA Staclot APC-R. Blood Coagul Fibrinolysis 1998; 09: 355-9.
24 Faure-Delanef L, Quere I, Zouali H, Cohen D. Human longevity and R506Q factor V gene mutation [letter]. Thromb Haemost 1997; 78: 1160.
25 McNerlan SE, Crawford VL, Stout RW. Factor V Leiden in a healthy Northern Ireland elderly population [letter]. Age Ageing 1997; 26: 408-9.
26 Rees DC, Liu YT, Cox MJ, Elliott P, Wainscoat JS. Factor V Leiden and thermolabile methylenetetrahydrofolate reductase in extreme old age. Thromb Haemost 1997; 78: 1357-9.
27 Heijmans BT, Westendorp RG, Knook DL, Kluft C, Slagboom PE. The risk of mortality and the factor V Leiden mutation in a population-based cohort. Thromb Haemost 1998; 80: 607-9.
28 Cushman M, Rosendaal FR, Psaty BM, Cook EF, Valliere J, Kuller LH. et al. Factor V Leiden is not a risk factor for arterial vascular disease in the elderly: results from the Cardiovascular Health Study. Thromb Haemost 1998; 79: 912-5.
29 Koeleman BP, Reitsma PH, Allaart CF, Bertina RM. Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families. Blood 1994; 84: 1031-5.
30 Zoller B, Berntsdotter A, Garcia dF, Dahlback B. Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S. Blood 1995; 85: 3518-23.
31 Ehrenforth S, Ludwig G, Klinke S, Krause M, Scharrer I, Nowak-Gottl U. The prothrombin 20210 A allele is frequently coinherited in young carriers of the factor V Arg 506 to Gln mutation with venous thrombophilia. Blood 1998; 91: 2209-10.
32 Zoller B, Garcia dF, Hillarp A, Dahlback B. Thrombophilia as a multigenic disease. Haematologica 1999; 84: 59-70.
33 Middeldorp S, Henkens CM, Koopman MM, van Pampus EC, Hamulyak K, van der Meer J. et al. The incidence of venous thromboembolism in family members of patients with factor V Leiden mutation and venous thrombosis. Ann Intern Med 1998; 128: 15-20.
34 Simioni P, Sanson BJ, Prandoni P, Tormene D, Friederich PW, Girolami B. et al. Incidence of venous thromboembolism in families with inherited thrombophilia. Thromb Haemost 1999; 81: 198-202.