D-Dimer as a Risk Factor for Deep Vein Thrombosis: The Leiden Thrombophilia Study

Astrid C. M. Andreescu; Mary Cushman; Frits R. Rosendaal

doi:10.1055/s-0037-1612942

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2002; 87(01): 47-51
DOI: 10.1055/s-0037-1612942

Review Article

Schattauer GmbH

D-Dimer as a Risk Factor for Deep Vein Thrombosis: The Leiden Thrombophilia Study

Astrid C. M. Andreescu

¹ Department of Medicine, Division of Hematology, Oncology, and

,

Mary Cushman

¹ Department of Medicine, Division of Hematology, Oncology, and

² Department of Pathology, University of Vermont, Burlington, VT, USA

,

Frits R. Rosendaal

³ Department of Clinical Epidemiology and the Hemostasis and Thrombosis Research Center Leiden University Medical Center, Leiden, The Netherlands

› Institutsangaben

Abstract

Summary

We studied the association of D-dimer with the risk of deep vein thrombosis (DVT). D-dimer was measured in 474 patients more than 6 months after diagnosis of a first DVT and in 474 age-and sexmatched controls. For D-dimer above the 70th percentile (130.5 ng/ml), the odds ratio (OR) for DVT was 2.2 (95% CI, 1.6-2.9). The association was unchanged with adjustment for other risk factors. Excluding participants with Factor V Leiden, prothrombin 20210A, or factors VIIIc or IX above the 90th percentile, the OR was 1.6 (95% CI, 1.1-2.3). The risks of DVT with the joint presence of high D-dimer and either factor V Leiden or prothrombin 20210A were increased 12.4-fold (95% CI 5.6-27.7) and 7.2-fold (95% CI 2.1-25.1), respectively. Higher Ddimer concentration was associated with the risk of DVT, and was supra-additive to the risks associated with factor V Leiden and the prothrombin 20210A variant. Persistence of this association in the absence of other hemostatic risk factors for DVT suggests that high D-dimer may be related to other, as yet unknown, risk factors for venous thrombosis. Confirmation of these findings is desirable.

Keywords

Deep vein thrombosis - D-dimer - blood coagulation - risk factor

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Referenzen

References
1 Bertina RM, Koeleman BP, 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: 64-7.
2 Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variant in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698-703.
3 Lane D, Mannucci P, Bauer K, Bertina R, Bochov N, Boulyjenkov V, Chandy M, Dahlback B, Ginter E, Miletich J, Rosendaal F, Seligsohn U. Inherited thrombophilia: Part 1. Thromb Haemost 1996; 76: 651-62.
4 Kraaijenhagen RA, in’t PSAnker, Koopman MM, Reitsma PH, Prins MH, ven Aden Ende, Buller HR. High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism. Thromb Haemost 2000; 83: 5-9.
5 van Hylckama AVlieg, ven Ider Linden, Bertina R, Rosendaal F. High levels of factor IX increase the risk of venous thrombosis. Blood 2000; 95: 3678-82.
6 Prins M, Hirsh J. A critical review of the evidence supporting a relationship between impaired fibrinolytic activity and venous thromboembolism. Arch Intern Med 1991; 151: 1721-31.
7 Ridker P, Vaughn D, Stampfer M, Manson J, Shen C, Newcomer L, Goldhaber S, Hennekens C. Baseline fibrinolytic state and the risk of future venous thrombosis: a prospective study of endogenous tissue-type plasminogen activator and plasminogen activator inhibitor. Circulation 1992; 85: 1822-7.
8 Schulman S, Wiman B. The significance of hypofibrinolysis for the risk of recurrence of venous thromboembolism Duration of Anticoagulation (DURAC) Trial Study Group. Thromb Haemost 1996; 75: 607-11.
9 Lowe G, Woodward M, Vessey M, Rumley A, Gough P, Daly E. Thrombotic variables and risk of idiopathic venous thromboembolism in women aged 45-64 years: relationships to hormone replacement therapy. Thromb Haemost 2000; 83: 530-5.
10 Declerck PJ, Mombaerts P, Holvoet P, De Mol M, Collen D. Fibrinolytic response and fibrin fragment D-dimer levels in patients with deep vein thrombosis. Thromb Haemost 1987; 58: 1024-9.
11 Korninger C, Lechner K, Niessner H, Gossinger H, Kundi M. Impaired fibrinolytic capacity predisposes for recurrence of venous thrombosis. Thromb Haemost 1984; 1984: 127-30.
12 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.
13 Bovill E, Hasstedt S, Callas P, Valliere J, Scott B, Bauer K, Long G. The G20210A prothrombin polymorphism is not associated with increased thromboembolic risk in a large protein C deficient kindred. Thromb Haemost 2000; 83: 366-70.
14 Cushman M, Cornell ES, Macy EM, Psaty BM, Tracy RP. Correlates of the fibrin fragment D-dimer, a measure of fibrinolysis, in an elderly cohort free of prevalent cardiovascular disease [abstract]. Circulation [Suppl 1] 1995; 92: 624.
15 Lee AJ, Fowkes GR, Lowe GD, Rumley A. Determinants of fibrin D-dimer in the Edinburgh Artery Study. Arterioscler Thromb Vasc Biol 1995; 15: 1094-7.
16 Lensen R, Rosendaal F, de Ronde H, Vandenbroucke J, Bertina R. Factor V Leiden: increased risk of venous thrombosis in affected relatives of unselected carriers with a first deep vein thrombosis. Thromb Haemost 2000; 83: 817-21.
17 Lensen R, Rosendaal F, de Ronde H, Vandenbroucke J, Bertina R. Factor V Leiden: the venous thrombotic risk in thrombophilic families. Br J Haematol 2000; 110: 939-45.
18 Cushman M, Lemaitre RN, Kuller LH, Psaty BM, Macy EM, Sharrett AR, Tracy RP. Fibrinolytic activation markers predict myocardial infarction in the elderly: the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol 1999; 19: 493-8.
19 Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, Rumley A, Lowe G. Fibrin D-dimer and coronary heart disease: prospective study and meta-analysis. Circulation 2001; 103: 2323-7.