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Clinical Chemistry and Laboratory Medicine (CCLM)

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Volume 44, Issue 5 (May 2006)


Factor V Leiden, prothrombin G20210A substitution and hormone therapy: indications for molecular screening

Maria Grazia Andreassi
  • Laboratory of Cellular Biology and Genetics, CNR-Institute of Clinical Physiology, “G. Pasquinucci” Hospital, Massa, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Nicoletta Botto
  • Laboratory of Cellular Biology and Genetics, CNR-Institute of Clinical Physiology, “G. Pasquinucci” Hospital, Massa, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Silvia Maffei
Published Online: 2011-09-21 | DOI: https://doi.org/10.1515/CCLM.2006.103


Venous thromboembolism is a well-known complication of oral contraception and hormonal replacement therapy. Inherited thrombophilia is viewed as an important determinant in modulating the effects of estrogens on thrombotic risk. An increasing number of kits for thrombophilic mutations [factor V Leiden, G20210A prothrombin and methylenetetrahydrofolate reductase (MTHFR) C677T genes] are becoming commercially available, and screening for inherited thrombotic risk is among the most requested genetic tests in molecular diagnostic laboratories. However, the question of routine genetic screening for thrombophilia before prescribing hormones is still a matter of debate. The purpose of this article is to discuss the usefulness and practical applications of thrombotic genetic testing to identify which women should be tested to improve both the safety and efficacy of individualized estrogen therapy.

Keywords: genetic testing; hormonal replacement therapy; inherited thrombophilia; oral contraception, thrombotic risk


  • 1.

    Gomes MP, Deitcher SR. Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy: a clinical review. Arch Intern Med 2004; 164:1965–76.Google Scholar

  • 2.

    Herrington DM, Klein KP. Invited review: pharmacogenetics of estrogen replacement therapy. J Appl Physiol 2001; 91:2776–84.Google Scholar

  • 3.

    Braunstein JB, Kershner DW, Bray P, Gerstenblith G, Schulman SP, Post WS, et al. Interaction of hemostatic genetics with hormone therapy: new insights to explain arterial thrombosis in postmenopausal women. Chest 2002; 121:906–20.Google Scholar

  • 4.

    Kottke-Marchant K. Genetic polymorphisms associated with venous and arterial thrombosis: an overview. Arch Pathol Lab Med 2002; 126:295–304.Google Scholar

  • 5.

    Endler G, Mannhalter C. Polymorphisms in coagulation factor genes and their impact on arterial and venous thrombosis. Clin Chim Acta 2003; 330:31–55.Google Scholar

  • 6.

    Federici C, Gianetti J, Andreassi MG. Genomic medicine and thrombotic risk: who, when, how and why? Int J Cardiol 2006; 106:3–9.CrossrefGoogle Scholar

  • 7.

    Schifreen RS, Storts DR, Buller AM. The challenge of using SNPs in the understanding and treatment of disease. Biotechniques 2002; 18:20–1.Google Scholar

  • 8.

    Fleming DA. Ethical considerations of genetic testing. J Clin Ethics 2002; 13:316–23.Google Scholar

  • 9.

    Bates BR, Templeton A, Achter PJ, Harris TM, Condit CM. What does “a gene for heart disease” mean? A focus group study of public understandings of genetic risk factors. Am J Med Genet 2003; 119:156–61.Google Scholar

  • 10.

    Jordan WM. Pulmonary embolism. Lancet 1961; 2:1146–7.CrossrefGoogle Scholar

  • 11.

    Rosendaal FR, Helmerhorst FM, Vandenbroucke JP. Female hormones and thrombosis. Arterioscler Thromb Vasc Biol 2002; 22:201–10.CrossrefGoogle Scholar

  • 12.

    Jick H, Jick SS, Gurewich V, Myers MW, Vasilakis C. Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet 1995; 346:1589–93.Google Scholar

  • 13.

    Vandenbroucke JP, Rosing J, Bloemenkamp KW, Middeldorp S, Helmerhorst FM, Bouma BN, et al. Oral contraceptives and the risk of venous thrombosis. N Engl J Med 2001; 344:1527–35.Google Scholar

  • 14.

    Jick H, Kaye JA, Vasilakis-Scaramozza C, Jick SS. Risk of venous thromboembolism among users of third generation oral contraceptives compared with users of oral contraceptives with levonorgestrel before and after 1995: cohort and case-control analysis. Br Med J 2000; 321:1190–5.Google Scholar

  • 15.

    Rosendaal FR, Helmerhorst FM, Vandenbroucke JP. Oral contraceptives, hormone replacement therapy and thrombosis. Thromb Haemost 2001; 86:112–23.Google Scholar

  • 16.

    Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. J Am Med Assoc 2002; 288:321–33.Google Scholar

  • 17.

    Grady D, Wenger NK, Herrington D, Khan S, Furberg C, Hunninghake D, et al. Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The Heart and Estrogen/progestin Replacement Study. Ann Intern Med 2000; 132:689–96.Google Scholar

  • 18.

    Herrington DM, Vittinghoff E, Howard TD, Major DA, Owen J, Reboussin DM, et al. Factor V Leiden, hormone replacement therapy, and risk of venous thromboembolic events in women with coronary disease. Arterioscler Thromb Vasc Biol 2002; 22:1012–7.CrossrefGoogle Scholar

  • 19.

    Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. J Am Med Assoc 1998; 280:605–13.Google Scholar

  • 20.

    Herrington DM. The HERS trial results: paradigms lost? Heart and Estrogen/progestin Replacement Study. Ann Intern Med 1999; 131:463–6.Google Scholar

  • 21.

    Renner W, Cichocki L, Forjanics A, Koppel H, Gasser R, Pilger E. G-455A polymorphism of the fibrinogen beta gene and deep vein thrombosis. Eur J Clin Invest 2002; 32:755–8.Google Scholar

  • 22.

    Sartori MT, Danesin C, Saggiorato G, Tormene D, Simioni P, Spiezia L, et al. The PAI-1 gene 4G/5G polymorphism and deep vein thrombosis in patients with inherited thrombophilia. Clin Appl Thromb Hemost 2003; 9:299–307.Google Scholar

  • 23.

    Fatini C, Gensini F, Sticchi E, Battaglini B, Prisco D, Fedi S, et al. ACE DD genotype: an independent predisposition factor to venous thromboembolism. Eur J Clin Invest 2003; 33:642–7.CrossrefGoogle Scholar

  • 24.

    Zidane M, de Visser MC, ten Wolde M, Vos HL, de Monye W, Bertina RM, et al. Frequency of the TAFI –438 G/A and factor XIIIA Val34Leu polymorphisms in patients with objectively proven pulmonary embolism. Thromb Haemost 2003; 90:439–45.Google Scholar

  • 25.

    Komanasin N, Catto AJ, Futers TS, van Hylckama Vlieg A, Rosendaal FR, Ariens RA. A novel polymorphism in the factor XIII B-subunit (His95Arg): relationship to subunit dissociation and venous thrombosis. J Thromb Haemost 2005; 3:2487–96.Google Scholar

  • 26.

    van Wijk R, Nieuwenhuis K, van den Berg M, Huizinga EG, van der Meijden BB, Kraaijenhagen RJ, et al. Five novel mutations in the gene for human blood coagulation factor V associated with type I factor V deficiency. Blood 2001; 98:358–67.CrossrefGoogle Scholar

  • 27.

    Mingozzi F, Legnani C, Lunghi B, Scanavini D, Castoldi E, Palareti G, et al. A FV multiallelic marker detects genetic components of APC resistance contributing to venous thromboembolism in FV Leiden carriers. Thromb Haemost 2003; 89:983–9.Google Scholar

  • 28.

    Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thromb Diath Haemorrh 1965; 13:516–30.Google Scholar

  • 29.

    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.Google Scholar

  • 30.

    Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation 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.Google Scholar

  • 31.

    Rees DC. World distribution of factor V Leiden. Lancet 1995; 346:1133–4.Google Scholar

  • 32.

    Tripodi A, Mannucci PM. Laboratory investigation of thrombophilia. Clin Chem 2001; 47:1597–606.Google Scholar

  • 33.

    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.Google Scholar

  • 34.

    Vandenbroucke JP, Koster T, Briet E, Reitsma PH, Bertina RM, Rosendaal FR. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet 1994; 344:1453–7.Google Scholar

  • 35.

    Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Buller HR, Vandenbroucke JP. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet 1995; 346:1593–6.Google Scholar

  • 36.

    Andersen BS, Olsen J, Nielsen GL, Steffensen FH, Sorensen HT, Baech J, et al. Third generation oral contraceptives and heritable thrombophilia as risk factors of non-fatal venous thromboembolism. Thromb Haemost 1998; 79:28–31.Google Scholar

  • 37.

    Martinelli I, Cattaneo M, Taioli E, De Stefano V, Chiusolo P, Mannucci PM. Interaction between the G20210A mutation of the prothrombin gene and oral contraceptive use in deep vein thrombosis. Arterioscler Thromb Vasc Biol 1999; 19:700–3.Google Scholar

  • 38.

    Spannagl M, Heinemann LA, Schramm W. Are factor V Leiden carriers who use oral contraceptives at extreme risk for venous thromboembolism? Eur J Contracept Reprod Health Care 2000; 5:105–12.CrossrefGoogle Scholar

  • 39.

    Wu O, Robertson L, Langhorne P, Twaddle S, Lowe GD, Clark P, et al. Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thromb Haemost 2005; 94:17–25.Google Scholar

  • 40.

    Rintelen C, Mannhalter C, Ireland H, Lane DA, Knobl P, Lechner K, et al. Oral contraceptives enhance the risk of clinical manifestation of venous thrombosis at a young age in females homozygous for factor V Leiden. Br J Haematol 1996; 93:487–90.Google Scholar

  • 41.

    Lippi G, Manzato F, Brocco G, Franchini M, Guidi G. Prothrombotic effects and clinical implications of third-generation oral contraceptives use. Blood Coagul Fibrinolysis 2002; 13:69–72.CrossrefGoogle Scholar

  • 42.

    Rosing J, Tans G, Nicolaes GA, Thomassen MC, van Oerle R, van der Ploeg PM, et al. Oral contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second- and third-generation oral contraceptives. Br J Haematol 1997; 97:233–8.Google Scholar

  • 43.

    Rosendaal FR, Vessey M, Rumley A, Daly E, Woodward M, Helmerhorst FM, et al. Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis. Br J Haematol 2002; 116:851–4.Google Scholar

  • 44.

    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.Google Scholar

  • 45.

    Glueck CJ, Wang P, Fontaine RN, Tracy T, Sieve-Smith L, Lang JE. Effect of exogenous estrogen on atherothrombotic vascular disease risk related to the presence or absence of the factor V Leiden mutation (resistance to activated protein C). Am J Cardiol 1999; 84:549–54.CrossrefGoogle Scholar

  • 46.

    Franco RF, Trip MD, ten Cate H, van den Ende A, Prins MH, Kastelein JJ, et al. The 20210 G→A mutation in the 3′-untranslated region of the prothrombin gene and the risk for arterial thrombotic disease. Br J Haematol 1999; 104:50–4.Google Scholar

  • 47.

    De Stefano V, Martinelli I, Mannucci PM, Paciaroni K, Chiusolo P, Casorelli I, et al. The risk of recurrent deep venous thrombosis among heterozygous carriers of both factor V Leiden and the G20210A prothrombin mutation. N Engl J Med 1999; 341:801–6.Google Scholar

  • 48.

    De Stefano V, Zappacosta B, Persichilli S, Rossi E, Casorelli I, Paciaroni K, et al. Prevalence of mild hyperhomocysteinaemia and association with thrombophilic genotypes (factor V Leiden and prothrombin G20210A) in Italian patients with venous thromboembolic disease. Br J Haematol 1999; 106:564–8.Google Scholar

  • 49.

    Martinelli I, Bucciarelli P, Margaglione M, De Stefano V, Castaman G, Mannucci PM. The risk of venous thromboembolism in family members with mutations in the genes of factor V or prothrombin or both. Br J Haematol 2000; 111:1223–9.Google Scholar

  • 50.

    Emmerich J, Rosendaal FR, Cattaneo M, Margaglione M, De Stefano V, Cumming T, et al. Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism – pooled analysis of 8 case-control studies including 2310 cases and 3204 controls. Study Group for Pooled-Analysis in Venous Thromboembolism. Thromb Haemost 2001; 86:809–16 (Erratum in: Thromb Haemost 2001;86:1598).Google Scholar

  • 51.

    Legnani C, Palareti G, Guazzaloca G, Cosmi B, Lunghi B, Bernardi F, et al. Venous thromboembolism in young women; role of thrombophilic mutations and oral contraceptive use. Eur Heart J 2002; 23:984–90.CrossrefGoogle Scholar

  • 52.

    Martinelli I, Sacchi E, Landi G, Taioli E, Duca F, Mannucci PM. High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives. N Engl J Med 1998; 338:1793–7.Google Scholar

  • 53.

    Straczek C, Oger E, Beau Yon de Jonage-Canonico M, Plu-Bureau G, Conard J, Meyer G, et al. Estrogen and Thromboembolism Risk (ESTHER) Study Group. Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration. Circulation 2005; 112:3495–500.CrossrefGoogle Scholar

  • 54.

    Glueck CJ, Wang P, Fontaine RN, Tracy T, Sieve-Smith L, Lang JE. The effect of exogenous estrogen on atherothrombotic vascular disease risk relates to the presence or absence of the 20210 G/A prothrombin gene mutation: a cross-sectional study of 230 hyperlipidemic women. Circulation 2000; 102:II278–9.Google Scholar

  • 55.

    Psaty BM, Smith NL, Lemaitre RN, Vos HL, Heckbert SR, LaCroix AZ, et al. Hormone replacement therapy, prothrombotic mutations, and the risk of incident nonfatal myocardial infarction in postmenopausal women. J Am Med Assoc 2001; 285:906–13.Google Scholar

  • 56.

    Fermo I, D'Angelo SV, Paroni R, Mazzola G, Calori G, D'Angelo A. Prevalence of moderate hyperhomocysteinemia in patients with early-onset venous and arterial occlusive disease. Ann Intern Med 1995; 123:747–53.Google Scholar

  • 57.

    den Heijer M, Koster T, Blom HJ, Bos GM, Briet E, Reitsma PH, et al. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med 1996; 334:759–62.Google Scholar

  • 58.

    den Heijer M, Rosendaal FR, Blom HJ, Gerrits WB, Bos GM. Hyperhomocysteinemia and venous thrombosis: a meta-analysis. Thromb Haemost 1998; 80:874–7.Google Scholar

  • 59.

    Martinelli I, Battaglioli T, Pedotti P, Cattaneo M, Mannucci PM. Hyperhomocysteinemia in cerebral vein thrombosis. Blood 2003; 102:1363–6.CrossrefGoogle Scholar

  • 60.

    Haynes WG. Hyperhomocysteinemia, vascular function and atherosclerosis: effects of vitamins. Cardiovasc Drugs Ther 2002; 16:391–9.CrossrefGoogle Scholar

  • 61.

    Gellekink H, den Heijer M, Heil SG, Blom HJ. Genetic determinants of plasma total homocysteine. Semin Vasc Med 2005; 5:98–109.CrossrefGoogle Scholar

  • 62.

    Kang SS, Zhou J, Wong PW, Kowlisyn J, Strokosch G. Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet 1988; 48:536–45.Google Scholar

  • 63.

    Franco RF, Araujo AG, Guerreiro JF, Elion J, Zago MA. Analysis of the 677 C→T mutation of the methylenetetrahydrofolate reductase gene in different ethnic groups. Thromb Haemost 1998; 79:119–21.Google Scholar

  • 64.

    Key NS, McGlennen RC. Hyperhomocyst(e)inemia and thrombophilia. Arch Pathol Lab Med 2002; 126:1367–75.Google Scholar

  • 65.

    Kluijtmans LA, Den Heijer M, Reitsma PH, Heil SG, Blom HJ, Rosendaal FR. Thermolabile methylenetetrahydrofolate reductase and factor V Leiden in the risk of deep-vein thrombosis. Thromb Haemost 1998; 79:254–8.Google Scholar

  • 66.

    Domagala TB, Adamek L, Nizankowska E, Sanak M, Szczeklik A. Mutations C677T and A1298C of the 5,10-methylenetetrahydrofolate reductase gene and fasting plasma homocysteine levels are not associated with the increased risk of venous thromboembolic disease. Blood Coagul Fibrinolysis 2002; 13:423–31.Google Scholar

  • 67.

    Zalavras ChG, Giotopoulou S, Dokou E, Mitsis M, Ioannou HV, Tzolou A, et al. Lack of association between the C677T mutation in the 5,10-methylenetetrahydrofolate reductase gene and venous thromboembolism in Northwestern Greece. Int Angiol 2002; 21:268–71.Google Scholar

  • 68.

    Morelli VM, Lourenco DM, D'Almeida V, Franco RF, Miranda F, Zago MA, et al. Hyperhomocysteinemia increases the risk of venous thrombosis independent of the C677T mutation of the methylenetetrahydrofolate reductase gene in selected Brazilian patients. Blood Coagul Fibrinolysis 2002; 13:271–5.Google Scholar

  • 69.

    Ray JG, Langman LJ, Vermeulen MJ, Evrovski J, Yeo EL, Cole DE. Genetics University of Toronto Thrombophilia Study in Women (GUTTSI): genetic and other risk factors for venous thromboembolism in women. Curr Control Trials Cardiovasc Med 2001; 2:141–9.CrossrefGoogle Scholar

  • 70.

    Varela ML, Adamczuk YP, Forastiero RR, Martinuzzo ME, Cerrato GS, Pombo G, et al. Major and potential prothrombotic genotypes in a cohort of patients with venous thromboembolism. Thromb Res 2001; 104:317–24.CrossrefGoogle Scholar

  • 71.

    Frederiksen J, Juul K, Grande P, Jensen GB, Schroeder TV, Tybjaerg-Hansen A, et al. Methylenetetrahydrofolate reductase polymorphism (C677T), hyperhomocysteinemia, and risk of ischemic cardiovascular disease and venous thromboembolism: prospective and case-control studies from the Copenhagen City Heart Study. Blood 2004; 104:3046–51.Google Scholar

  • 72.

    Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J Thromb Haemost 2005; 3:292–9.CrossrefGoogle Scholar

  • 73.

    Sidney S, Petitti DB, Soff GA, Cundiff DL, Tolan KK, Quesenberry CP Jr. Venous thromboembolic disease in users of low-estrogen combined estrogen-progestin oral contraceptives. Contraception 2004; 70:3–10.CrossrefGoogle Scholar

  • 74.

    Brown CA, McKinney KQ, Young KB, Norton HJ. The C677T methylenetetrahydrofolate reductase polymorphism influences the homocysteine-lowering effect of hormone replacement therapy. Mol Genet Metab 1999; 67:43–8.Google Scholar

  • 75.

    Tanis BC, Blom HJ, Bloemenkamp DG, van den Bosch MA, Algra A, van der Graaf Y, et al. Folate, homocysteine levels, methylenetetrahydrofolate reductase (MTHFR) 677C→T variant, and the risk of myocardial infarction in young women: effect of female hormones on homocysteine levels. J Thromb Haemost 2004; 2:35–41.Google Scholar

  • 76.

    Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Vandenbroucke JP. Higher risk of venous thrombosis during early use of oral contraceptives in women with inherited clotting defects. Arch Intern Med 2000; 160:49–52.Google Scholar

  • 77.

    Konkle BA, Schafer AI. Hemostasis, thrombosis, fibrinolysis, and cardiovascular disease. In: Zipes D, Libby P, Bonow R, Branuwald E, editors. Braunwald's heart disease, 7th ed. Philadelphia, PA: Elsevier-Saunders, 2005:2067–92.Google Scholar

  • 78.

    Grody WW, Griffin JH, Taylor AK, Korf BR, Heit JA, ACMG Factor V Leiden Working Group. American College of Medical Genetics consensus statement on factor V Leiden mutation testing. Genet Med 2001; 3:139–48.CrossrefGoogle Scholar

  • 79.

    Kujovich JL. Hormones and pregnancy: thromboembolic risks for women. Br J Haematol 2004; 126:443–54.Google Scholar

  • 80.

    Mannucci PM. Laboratory detection of inherited thrombophilia: a historical perspective. Semin Thromb Hemost 2005; 31:5–10.CrossrefGoogle Scholar

  • 81.

    Hertzberg MS. Genetic testing for thrombophilia mutations. Semin Thromb Hemost 2005; 31:33–8.CrossrefGoogle Scholar

  • 82.

    Cosmi B, Coccheri S. Thrombophilia in young women candidate to the pill: reasons for and against screening. Pathophysiol Haemost Thromb 2002; 32:315–7.Google Scholar

  • 83.

    Wu O, Robertson L, Twaddle S, Lowe G, Clark P, Walker I, et al. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Screening for thrombophilia in high-risk situations: a meta-analysis and cost-effectiveness analysis. Br J Haematol 2005; 131:80–90.Google Scholar

  • 84.

    Martinelli I, De Stefano V, Taioli E, Paciaroni K, Rossi E, Mannucci PM. Inherited thrombophilia and first venous thromboembolism during pregnancy and puerperium. Thromb Haemost 2002; 87:791–5.Google Scholar

  • 85.

    Kupferminc MJ, Eldor A, Steinman N, Many A, Bar-Am A, Jaffa A, et al. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med 1999; 340:9–13.Google Scholar

  • 86.

    Blumenfeld Z. Thrombophilia-associated pregnancy wastage. Fertil Steril 1999; 72:765–74.CrossrefGoogle Scholar

  • 87.

    Caprini JA, Glase CJ, Anderson CB, Hathaway K. Laboratory markers in the diagnosis of venous thromboembolism. Circulation 2004; 109:I4–8.Google Scholar

  • 88.

    Dahlback 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 for activated protein C. Proc Natl Acad Sci USA 1993; 90:1004–8.CrossrefGoogle Scholar

  • 89.

    Tripodi A, Mannucci PM. Laboratory investigation of thrombophilia. Clin Chem 2001; 47:1597–606.Google Scholar

About the article

Corresponding author: Maria Grazia Andreassi, CNR-Institute of Clinical Physiology, G. Pasquinucci Hospital, Via Aurelia Sud-Montepepe, 54100 Massa, Italy Phone: +39-0585-493646, Fax: +39-0585-493601,

Received: 2006-01-10

Accepted: 2006-02-06

Published Online: 2011-09-21

Published in Print: 2006-05-01

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2006.103.

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