Relevance of Inherited Risk Factors in Young Patients with Deep-Vein Thrombosis

Abstract

The relevance of congenital thrombophilia in the pathogenesis of venous thromboembolism in young patients is still debated. In a case-control study, plasma antigen and activity of antithrombin, protein C, and plas minogen, as well as total and free protein S were mea sured in a series of 166 consecutive outpatients aged less than 50 years, who underwent contrast venography be cause of clinically suspected deep-vein thrombosis (DVT). The presence of major acquired risk factors for venous thrombosis was also recorded. The association between DVT and inherited thrombophilia or acquired risk factors was initially described using crude odds ratios (OR). Subsequently, a logistic regression model was used to test their independence. Of the 166 patients included, venography showed an acute DVT in 73 (cases), whereas it was normal in the remaining 93 (controls). Major ac quired risk factors were identified in 51 cases and in 20 controls (crude OR: 8.5; 95% CI: 4.1-17.1). Inherited thrombophilia was detected in seven cases and in one control (crude OR: 9.8; 95% CI: 1.2-81.2). Inherited thrombophilia was equally distributed between patients with secondary and idiopathic DVT and was proved to be independent from acquired risk factors in the regression model. Inherited thrombophilia is an independent risk factor for DVT in young patients. However, its preva lence in unselected cases with the first episode of DVT is low.

Keywords

Key Words: Inherited thrombophilia Deep-vein thrombosis Case-control study.

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References

Cogo A. , Bernardi E. , Prandoni P. , et al. Acquired risk factors for deep-vein thrombosis in symptomatic outpatients. Arch Intern Med 1994;154:164.

Girolami A. The hereditary thrombosis. In: Thrombosis: an update . Neri Serneri GG , Gensini GF , Abbate R , Prisco D , eds. Florence: Scientific Press, 1992:89.

Demers C. , Ginsberg JS , Hirsh J. , Henderson P. , Blachman MA Thrombosis in an antithrombin-III-deficient person. Report of a large kindred and literature review. Ann Intern Med 1992 ;116:754.

Hirsh J. , Prins MH , Samama M. Approach to the thrombophilic patient. In: Hemostasis and thrombosis: basic principles and clinical practice. Colman RW , Hirsh J , Marder VJ , Salzman EW , eds. Philadelphia: J.B. Lippincott, 1994:1543.

Prandoni P. , Lensing Awa , Huisman MV , et al. A new computerized impedance plethysmograph: accuracy in the detection of proximal vein thrombosis in symptomatic outpatients. Thromb Haemost 1991 ;65:229.

Lensing Awa , Prandoni P. , Brandjes D. , et al. Detection of deep-vein thrombosis by real-time B-mode ultrasonography . N Engl J Med 1989;320:342.

Wells PS , Anderson DR , Lensing Awa , et al. Evaluation of the accuracy of impedance plethysmography (IPG) and compression ultrasound (CUS) in outpatients with suspected deep-vein thrombosis (DVT); a prospective paired design [Abstract]. Thromb Haemost 1993;69:1355.

Lensing Awa , Büller HR , Prandoni P. , et al. Contrast venography, the gold standard for the diagnosis of deep-vein thrombosis: improvement in observer agreement. Thromb Haemost 1992;67:8.

Peters M. , Breederveld C. , Kahlè LH , ten Cate JW Rapid microanalysis of coagulation parameters by automated chromogenic substrate methods, application in neonatal patients. Thromb Res 1982;28:773.

10.

Sturk A. , Morrien-Salomons WM , Huisman MV , Borm Jjj , Büller HR , ten Cate JW Analytical and clinical evaluation of commercial protein C assays . Clin Chim Acta 1987;165:263.

11.

Girolami A. , Simioni P. , Lazzaro AR , Cordiano I. Severe arterial cerebral thrombosis in a patient with protein S deficiency (moderately reduced total and markedly reduced free protein S): a family study. Thromb Haemost 1988;61:144.

12.

Engesser L. , Broekmans AW , Briët E. , Brommer Ejp , Bertina RM Hereditary protein S deficiency: clinical manifestations. Ann Intern Med 1987;106:677.

13.

Heijboer H. , Brandjes Dpm , Büller HR , Sturk A. , ten Cate JW Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep vein thrombosis. N Engl J Med 1990;323:1512.

14.

Ben-Tal O. , Zivelin A. , Seligsohn U. The relative frequency of hereditary thrombotic disorders among 107 patients with thrombophilia in Israel. Thromb Haemost 1989 ;61 ;50.

15.

Comp PC Hereditary disorders predisposing to thrombosis. Prog Thromb Hemost 1986;8:71.

16.

Mannucci PM , Tripodi A. Laboratory screening of inherited thrombotic syndrome. Thromb Haemost 1987;57:247.

17.

Gladson CL , Griffin JH , Hach V. , Beck KH , Scharrer I. The incidence of protein C and protein S deficiency in young thrombotic patients . Blood 1985;66(Suppl I):350a.

18.

Broekmans AW , van der Linden IK , Jansen-Koeter Y. , Bertina RM Prevalence of protein C and protein S deficiency in patients with thrombotic disease. Thromb Res 1986;(Suppl VI):135.

19.

Gladson CL , Scharrer I. , Hach V. , Beck KH , Griffin JH The frequency of type I heterozygous protein S and protein C deficiency in 141 unrelated young patients with venous thrombosis. Thromb Haemost 1988;59:18.

20.

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.

21.

Voorberg J. , Roelse J. , Koopman R. , Büller HR , Berends F. , ten Cate JW , Mertens K. , van Mourik JA Association of idiopathic venous thromboembolism with single point-mutation at Arg506 of factor V. Lancet 1994;343:1535.

22.

Zöller B. , Dahlbäck B. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet 1994 ;343:1536.

23.

Svensson PJ , Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994;330: 517.

24.

Koster T. , Rosendaal FR , de Ronde H. , Briët E. , Vandenbroucke JP , Bertina RM Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden thrombophilia study. Lancet 1993 ;342:1503.

25.

Prandoni P. , Lensing Awa , Cogo A. , et al. The clinical course of deep-vein thrombosis in symptomatic patients . (submitted).