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Inherited Thrombophilia: Key Points for Genetic Counseling

  • Professional Development Paper
  • Published:
Journal of Genetic Counseling

With the evolution of medical genetics to focus on highly prevalent, multifactorial conditions, it is inevitable that genetic counselors will be called upon to participate in the evaluation and counseling of individuals with inherited thrombophilia. The purpose of this review is to educate the genetic counselor on key issues related to risk assessment and genetic counseling for hereditary thrombophilia. The information contained in this document is derived from an extensive review of the literature, as well as the author's personal expertise. Upon completion of this review, the genetic counselor will be able to: a) describe inherited and acquired risk factors for thrombosis, b) collect and interpret personal and family histories to assess risk related to hereditary thrombophilia, c) discuss the potential advantages and disadvantages of thrombophilia testing, including psychosocial aspects and implications for medical management, and d) identify educational and support resources for patients and families.

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REFERENCES

  • ACOG practice bulletin: Management of recurrent pregnancy loss. Number 24, February 2001. (Replaces Technical Bulletin Number 212, September 1995). American College of Obstetricians and Gynecologists. (2002). Int J Gynaecol Obstet, 78(2), 179–190.

    Google Scholar 

  • ACOG Practice Bulletin #68: Antiphospholipid syndrome. (2005). Obstet Gynecol, 106(5 Pt 1), 1113–1121.

    Google Scholar 

  • Agorastos, T., Karavida A., Lambropoulos A., Constantinidis, T., Tzitzimikas S., & Chrisafi S., et al. (2002). Factor V Leiden and prothrombin G20210A mutations in pregnancies with adverse outcome. J Matern Fetal Neonatal Med, 12(4), 267–273.

    PubMed  CAS  Google Scholar 

  • Andersen, B. S., & Olsen, J. (1998). Oral contraception and factor V Leiden mutation in relation to localization of deep vein thrombosis. Thromb Res, 90(4), 191–194.

    PubMed  CAS  Google Scholar 

  • Anderson, F. A., Jr., Wheeler, H. B., Goldberg, R. J., Hosmer, D. W., Forcier, A., & Patwardhan, N. A. (1991). Physician practices in the prevention of venous thromboembolism. Ann Intern Med, 115(8), 591–595.

    PubMed  Google Scholar 

  • Balasch, J., Reverter, J. C., Fabregues, F., Tassies, D., Rafel, M., Creus, M., & Vanrell, J. A. (1997). First-trimester repeated abortion is not associated with activated protein C resistance. Hum Reprod, 12(5), 1094–1097.

    PubMed  CAS  Google Scholar 

  • Bank, I., Scavenius, M. P., Buller, H. R., & Middeldorp, S. (2004). Social aspects of genetic testing for factor V Leiden mutation in healthy individuals and their importance for daily practice. Thromb Res, 113(1), 7–12.

    PubMed  CAS  Google Scholar 

  • Barbour, L. A. (2001). ACOG practice bulletin. Thrombembolism in pregnancy. Int J Gynaecol Obstet, 75(2), 203–212.

    PubMed  CAS  Google Scholar 

  • Bates, S. M., Greer, I. A., Hirsh, J., & Ginsberg, J. S. (2004). Use of antithrombotic agents during pregnancy, the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest, 126(3 Suppl), 627S–644S.

    Google Scholar 

  • Bauer, K. A. (2001). The thrombophilias: well-defined risk factors with uncertain therapeutic implications. Ann Intern Med, 135(5), 367–373.

    PubMed  CAS  Google Scholar 

  • Beauchamp, N. J., Dykes, A. C., Parikh, N., Campbell Tait, R., & Daly, M. E. (2004). The prevalence of, and molecular defects underlying, inherited protein S deficiency in the general population. Br J Haematol, 125(5), 647–654.

    PubMed  CAS  Google Scholar 

  • Bertina, R. M., Koeleman, B. P., Koster, T., Rosendaal, F. R., Dirven, R. J., de Ronde, H., Van Der Velden, P. A., & Reitsma, P. H. (1994). Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature, 369(6475), 64–67.

    PubMed  CAS  Google Scholar 

  • Bonaa, K., Njolstad I., Ueland, P., Schirmer, H., Tverdal, A., Steigen, T., et al. (2006). Homocysteine lowering and cardiovascular events after acute myocardial infarction. NEJM, (354), 1578–1588.

    PubMed  CAS  Google Scholar 

  • Bos, M. J., Heijer, M., Willems, H., Blom H., Gerrits W., Cattaneo M., et al. (2004). Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: A first randomized, placebo-controlled, double-blind trial. Blood, 104, 142a.

    Google Scholar 

  • Botto, L. D., & Yang, Q. (2000). 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: A HuGE review. Am J Epidemiol, 151(9), 862–877.

    PubMed  CAS  Google Scholar 

  • Brenner, B. R., Nowak-Gottl, U., Kosch, A., Manco-Johnson, M., & Laposata, M. (2002). Diagnostic studies for thrombophilia in women on hormonal therapy and during pregnancy, and in children. Arch Pathol Lab Med, 126(11), 1296–1303.

    PubMed  Google Scholar 

  • Brenner, B., Horrman, R., Carp, H., Dulitsky, M., Younis, J. (2005). Efficacy and safety of two doses of enoxaparin in women with thrombophilia and recurrent pregnancy losses: the LIVE-ENOX study. J Thromb Haemost, 3, 227–229.

    PubMed  CAS  Google Scholar 

  • Brill-Edwards, P., Ginsberg, J. S., Gent, M., Hirsh, J., Burrows, R., Kearon, C., Geerts, W., Kovacs, M., Weitz, J. I., Robinson, K. S., Whittom, R., & Couture, G. (2000). Safety of withholding heparin in pregnant women with a history of venous thromboembolism. Recurrence of clot in this pregnancy study group. N Engl J Med, 343(20), 1439–1444.

    PubMed  CAS  Google Scholar 

  • Caprini, J. A., Glase, C. J., Anderson, C. B., & Hathaway, K. (2004). Laboratory markers in the diagnosis of venous thromboembolism. Circulation, 109(12 Suppl 1), I4–I8.

    PubMed  CAS  Google Scholar 

  • College of American Pathologists Consensus Conference XXXVI: Diagnostic Issues in Thrombophilia. (2002). Arch Pathol Lab Med, 126(11), 1277–1433.

  • Copel, J. O. T. (2002). Deciphering the role of thrombophilias in recurrent miscarriage: impact on screening and treatment. Contemporary OB/GYN, 6, 122–132.

    Google Scholar 

  • Cosmi, B., Legnani, C., Bernardi, F., Coccheri, S., & Palareti, G. (2003). Role of family history in identifying women with thrombophilia and higher risk of venous thromboembolism during oral contraception. Arch Intern Med, 163(9), 1105–1109.

    PubMed  Google Scholar 

  • Cushman, M. (2005). Inhertied risk factors for venous thrombosis. Hematology (Am Soc Hematol Educ Program) 452–457.

  • De Stefano, V., Casorelli, I., Rossi, E., Zappacosta, B., & Leone, G. (2000). Interaction between hyperhomocysteinemia and inherited thrombophilic factors in venous thromboembolism. Semin Thromb Hemost, 26(3), 305–311.

    PubMed  CAS  Google Scholar 

  • De Stefano, V., Martinelli, I., Mannucci, P. M., Paciaroni, K., Chiusolo, P., Casorelli, I., Rossi, E., & Leone, G. (1999). The risk of recurrent deep venous thrombosis among heterozygous carriers of both factor V Leiden and the G20210A prothrombin mutation. N Engl J Med, 341(11), 801–806.

    PubMed  CAS  Google Scholar 

  • den Heijer, M., & Keijzer, M. B. (2001). Hyperhomocysteinemia as a risk factor for venous thrombosis. Clin Chem Lab Med, 39(8), 710–713.

    PubMed  CAS  Google Scholar 

  • Dizon-Townson, D., Miller, C., Sibai, B., Spong, C. Y., Thom, E., Wendel, G., et al. (2005). The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus. Obstet Gynecol, 106(3), 517–524.

    PubMed  CAS  Google Scholar 

  • Egeberg, O. (1965). Inherited Antithrombin Deficiency Causing Thrombophilia. Thromb Diath Haemorrh, 13, 516–530.

    PubMed  CAS  Google Scholar 

  • Eichinger, S., Pabinger, I., Stumpflen, A., Hirschl, M., Bialonczyk, C., Schneider, B., et al. (1997). The risk of recurrent venous thromboembolism in patients with and without factor V Leiden. Thromb Haemost, 77(4), 624–628.

    PubMed  CAS  Google Scholar 

  • Eichinger, S., & Kyrle, P. A. (2004). Prevention of deep vein thrombosis in orthopedic surgery. Eur J Med Res, 30;9(3), 112–118.

    Google Scholar 

  • Esfahani, S. T., Cogger, E. A., & Caudill, M. A. (2003). Heterogeneity in the prevalence of methylenetetrahydrofolate reductase gene polymorphisms in women of different ethnic groups. J Am Diet Assoc, 103(2), 200–207.

    PubMed  Google Scholar 

  • FDA Updates Labeling for Ortho Evra Contraceptive Patch. FDA News, November 10, 2005, http://www.fda.gov/bbs/topics/news/2005/NEW01262.html. Accessed September 15, 2006.

  • Franco, R. F., Santos, S. E., Elion, J., Tavella, M. H., & Zago, M. A. (1998). Prevalence of the G20210A polymorphism in the 3′-untranslated region of the prothrombin gene in different human populations. Acta Haematol, 100(1), 9–12.

    PubMed  CAS  Google Scholar 

  • Frosst, P., Blom, H. J., Milos, R., Goyette, P., Sheppard, C. A., Matthews, R. G., et al. (1995). A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase. Nat Genet, 10(1), 111–113.

    PubMed  CAS  Google Scholar 

  • Ginsberg, J. S., Kowalchuk G., & Hirsh J. (1989). Heparin therapy during pregnancy. Risks to the fetus and the mother. Arch Intern Med, 149, 2233–2236.

    PubMed  CAS  Google Scholar 

  • Geerts, W. H., Pineo, G. F., Heit, J. A., Bergqvist, D., Lassen, M. R., Colwell, et al. (2004). Prevention of venous thromboembolism: The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest, 126(3 Suppl), 338S–400S.

  • Goldhaber, S., & Fanikos, J. (2004). Prevention of deep vein thrombosis and pulmonary embolism. Circulation, 110, e445–e447.

    PubMed  Google Scholar 

  • Gompel, A., Levy, D. P., & Conard, J. (2002). Ovarian hyperstimulation and thrombosis. Women's Issues Thrombosis and Haemostasis, London: Martin Dunitz pp. 143–150

    Google Scholar 

  • Greaves, M., & Watson, H. G. (2003). Laboratory testing for prothrombotic states: Clinical utility. Curr Hematol Rep, 2(5), 429–434.

    PubMed  Google Scholar 

  • Greer, I. A. (2005). Venous thromboembolism and anticoagulant therapy in pregnancy. Gend Med, 2(Suppl A), S10–17.

    PubMed  Google Scholar 

  • Gris, J. C., Ripart-Neveu S., Maugard C., Tailland, M. L., Brun S., Courtieu, C., Biron C., et al. (1997). Respective evaluation of the prevalence of haemostasis abnormalities in unexplained primary early recurrent miscarriages. The Nimes Obstetricians and Haematologists (NOHA) Study. Thromb Haemost, 77(6), 1096–1103.

    PubMed  CAS  Google Scholar 

  • Gris, J. C., Mercier, E., Quere, I., Lavigne-Lissalde, G., Cochery-Nouvellon, E., Hoffet, M., et al. (2004). Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood, 103(10), 3695–3699.

    PubMed  CAS  Google Scholar 

  • Grody, W. W., Griffin, J. H., Taylor, A. K., Korf, B. R., & Heit, J. A. (2001). American College of Medical Genetics consensus statement on factor V Leiden mutation testing. Genet Med, 3(2), 139–148.

    PubMed  CAS  Google Scholar 

  • Haas, S. (2001). Prevention of venous thromboembolism: Recommendations based on the international consensus and the american college of chest physicians sixth consensus conference on antithrombotic therapy. Clin Appl Thromb Hemost, 7(3), 171–177.

    Google Scholar 

  • Heit, J. (2005). Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. Blood, 106, 267a.

    Google Scholar 

  • Heit, J. A. (2006). The epidemiology of venous thromboembolism in the community: Implications for prevention and management. J Thromb Thrombolysis, 21(1), 23–29.

    PubMed  Google Scholar 

  • Heit, J. A., O'Fallon, W. M., Petterson, T. M., Lohse, C. M., Silverstein, M. D., Mohr, D. 3rd et al., (2002). Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: A population-based study. Arch Intern Med, 162(11), 1245–1248.

    PubMed  Google Scholar 

  • Hellgren, M., Svensson, P. J., & Dahlback, B. (1995). Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and oral contraceptives. Am J Obstet Gynecol, 173(1), 210–213.

    PubMed  CAS  Google Scholar 

  • Hellmann, E. A., Leslie, N. D., & Moll, S. (2003). Knowledge and educational needs of individuals with the factor V Leiden mutation. J Thromb Haemost, 1(11), 2335–2339.

    PubMed  CAS  Google Scholar 

  • Hellmann, E., & Moll, S. (2004). Prothrombin 20210 mutation (Factor II Mutation). Circulation, 110, e15–e18.

    Google Scholar 

  • Hirsch, D. R., Mikkola, K. M., Marks, P. W., Fox, E. A., Dorfman, D. M., Ewenstein, B. M., et al. (1996). Pulmonary embolism and deep venous thrombosis during pregnancy or oral contraceptive use: Prevalence of factor V Leiden. Am Heart J, 131(6), 1145–1148.

    PubMed  CAS  Google Scholar 

  • Hirsh, J., Piovella, F., & Pini, M. (1989). Congenital antithrombin III deficiency. Incidence and clinical features. Am J Med, 87(3B), 34S–38S.

    PubMed  CAS  Google Scholar 

  • James, A., Abel, D., & Brancazio, L. (2005). Anticoagulants in Pregnancy. Obstet Gynecol Survey, 61(1), 59–69.

    Google Scholar 

  • Kamphuisen, P. W., & Rosendaal, F. R. (2004). Thrombophilia screening: A matter of debate. Neth J Med, 62(6), 180–187.

    PubMed  CAS  Google Scholar 

  • Kang, S. S., Zhou, J., Wong, P. W., Kowalisyn, J., & Strokosch, G. (1988). Intermediate homocysteinemia: A thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet, 43(4), 414–421.

    PubMed  CAS  Google Scholar 

  • Kearon, C. (1999). Initial treatment of venous thromboembolism. Thromb Haemost, 82(2), 887–891.

    PubMed  CAS  Google Scholar 

  • Klerk, M., Verhoef, P., Clarke, R., Blom, H. J., Kok, F. J., & Schouten, E. G. (2002). MTHFR 677C–>T polymorphism and risk of coronary heart disease: a meta-analysis. Jama, 288(16), 2023–2031.

    PubMed  CAS  Google Scholar 

  • Koster, T., Rosendaal, F. R., de Ronde, H., Briet, E., Vandenbroucke, J. P., & Bertina, R. M. (1993). Venous thrombosis due to poor anticoagulant response to activated protein C, leiden thrombophilia study. Lancet, 342(8886–8887), 1503–1506.

    PubMed  CAS  Google Scholar 

  • Kottke-Marchant, K. (2002). Genetic polymorphisms associated with venous and arterial thrombosis: An overview. Arch Pathol Lab Med, 126(3), 295–304.

    PubMed  CAS  Google Scholar 

  • Kottke-Marchant, K., & Comp, P. (2002). Laboratory issues in diagnosing abnormalities of protein C, thrombomodulin, and endothelial cell protein C receptor. Arch Pathol Lab Med, 126(11), 1337–1348.

    PubMed  CAS  Google Scholar 

  • Kottke-Marchant, K., & Duncan, A. (2002). Antithrombin deficiency: issues in laboratory diagnosis. Arch Pathol Lab Med, 126(11), 1326–1336.

    PubMed  CAS  Google Scholar 

  • Kupferminc, M. J., Eldor, A., Steinman, N., Many, A., Bar-Am, A., Jaffa, A., et al. (1999). Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med, 340(1), 9–13.

    PubMed  CAS  Google Scholar 

  • Kupferminc, M. J., Fait, G., Many, A., Gordon, D., Eldor, A., & Lessing, J. B. (2000). Severe preeclampsia and high frequency of genetic thrombophilic mutations. Obstet Gynecol, 96(1), 45–49.

    PubMed  CAS  Google Scholar 

  • Laurino, M. Y., Bennett, R. L., Saraiya, D. S., Baumeister, L., Doyle, D. L., Leppig, K., et al. (2005). Genetic evaluation and counseling of couples with recurrent miscarriage: recommendations of the national society of genetic counselors. J Genet Couns, 14(3), 165–181.

    PubMed  Google Scholar 

  • Lensen, R. P., Bertina, R. M., de Ronde, H., Vandenbroucke, J. P., & Rosendaal, F. R. (2000). Venous thrombotic risk in family members of unselected individuals with factor V Leiden. Thromb Haemost, 83(6), 817–821.

    PubMed  CAS  Google Scholar 

  • Lewis, S. J., Ebrahim, S., & Davey Smith, G. (2005). Meta-analysis of MTHFR 677C-T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate? BMJ, 331(7524), 1053.

    PubMed  CAS  Google Scholar 

  • Lindmarker, P., Schulman, S., Sten-Linder, M., Wiman, B., Egberg, N., & Johnsson, H. (1999). The risk of recurrent venous thromboembolism in carriers and non-carriers 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, 81(5), 684–689.

    PubMed  CAS  Google Scholar 

  • Lockwood, C. J. (2002). Inherited thrombophilias in pregnant patients: detection and treatment paradigm. Obstet Gynecol, 99(2), 333–341.

    PubMed  Google Scholar 

  • Makris, M., Rosendaal, F. R., & Preston, F. E. (1997). Familial thrombophilia: genetic risk factors and management. J Intern Med Suppl, 740, 9–15.

    PubMed  CAS  Google Scholar 

  • Marlar, R. A., Montgomery, R. R., & Broekmans, A. W. (1989). Report on the diagnosis and treatment of homozygous protein C deficiency: Report of the working party on homozygous protein C deficiency of the ICTH-subcommittee on protein C and protein S. Thromb Haemost, 61(3), 529–531.

    PubMed  CAS  Google Scholar 

  • Martinelli, I. (2001). Risk factors in venous thromboembolism. Thromb Haemost, 86(1), 395–403.

    PubMed  CAS  Google Scholar 

  • Martinelli, I. (2003). Pros and cons of thrombophilia testing: pros. J Thromb Haemost, 1(3), 410–411.

    PubMed  CAS  Google Scholar 

  • Martinelli, I., Taioli, E., Bucciarelli, P., Akhavan, S., & Mannucci, P. M. (1999). Interaction between the G20210A mutation of the prothrombin gene and oral contraceptive use in deep vein thrombosis. Arterioscler Thromb Vasc Biol, 19(3), 700–703.

    PubMed  CAS  Google Scholar 

  • Measurement and use of total plasma homocysteine. American Society of Human Genetics/American College of Medical Genetics Test and Transfer Committee Working Group. (1998). Am J Hum Genet, 63(5), 1541–1543.

    Google Scholar 

  • Middeldorp, S., Henkens, C. M., Koopman, M. M., van Pampus, E. C., Hamulyak, K., Van Der Meer, et al. (1998). The incidence of venous thromboembolism in family members of patients with factor V Leiden mutation and venous thrombosis. Ann Intern Med, 128(1), 15–20.

    PubMed  CAS  Google Scholar 

  • Miletich, J., Sherman, L., & Broze, G., Jr. (1987). Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med, 317(16), 991–996.

    Article  PubMed  CAS  Google Scholar 

  • Misita, C., & Moll, S. (2005). Antiphospholipid antibodies. Circulation, 112, e39–e44.

    PubMed  Google Scholar 

  • Moll, S. (2006). Thrombophilias–practical implications and testing caveats. J Thromb Thrombolysis, 21(1), 7–15.

    PubMed  Google Scholar 

  • Nicolaides, A. N. (2005). Thrombophilia and venous thromboembolism. international consensus statement: Guidelines according to scientific evidence. Int Angiol, 24(1), 1–26.

    PubMed  CAS  Google Scholar 

  • Ornstein, D. L., & Cushman M. (2003). Factor V Leiden. Circulation 107, e94–e97.

    PubMed  Google Scholar 

  • Ozcan, T., & Copel, J. (2002). Deciphering the role of thrombophilias in recurrent miscarriage. Contemporary OB/GYN, 6, 122–132.

    Google Scholar 

  • Poort, S. R., Rosendaal, F. R., Reitsma, P. H., & Bertina, R. M. (1996). 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, 88(10), 3698–3703.

    PubMed  CAS  Google Scholar 

  • Press, R. D., Bauer, K. A., Kujovich, J. L., & Heit, J. A. (2002). Clinical utility of factor V leiden (R506Q) testing for the diagnosis and management of thromboembolic disorders. Arch Pathol Lab Med, 126(11), 1304–1318.

    PubMed  Google Scholar 

  • Ray, J. G., Shmorgun, D., & Chan, W. S. (2002). Common C677T polymorphism of the methylenetetrahydrofolate reductase gene and the risk of venous thromboembolism: meta-analysis of 31 studies. Pathophysiol Haemost Thromb, 32(2), 51–58.

    PubMed  CAS  Google Scholar 

  • Reich, L. M., Bower, M., & Key, N. S. (2003). Role of the geneticist in testing and counseling for inherited thrombophilia. Genet Med, 5(3), 133–143.

    PubMed  Google Scholar 

  • Reid, W., & Perry, D. J. (2001). Internal jugular vein thrombosis following in vitro fertilization in a woman with protein S deficienty and heterozygosity for the prothrombin 3' UTR mutation, despite anticoagulation with heparin. Blood Coagulation and Fibrinolysis, 12, 487–489.

    PubMed  Google Scholar 

  • Rey, E., Kahn, S. R., David, M., & Shrier, I. (2003). Thrombophilic disorders and fetal loss: a meta-analysis. Lancet, 361(9361), 901–908.

    PubMed  Google Scholar 

  • Ridker, P. M., Goldhaber, S. Z., Danielson, E., Rosenberg, Y., Eby, C. S., Deitcher, S. R., Cushman, M., et al. (2003). Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med, 348(15), 1425–1434.

    PubMed  CAS  Google Scholar 

  • Ridker, P. M., Miletich, J. P., Hennekens, C. H., & Buring, J. E. (1997). Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening. Jama, 277(16), 1305–1307.

    PubMed  CAS  Google Scholar 

  • Ridker, P. M., Miletich, J. P., Stampfer, M. J., Goldhaber, S. Z., Lindpaintner, K., & Hennekens, C. H. (1995). Factor V Leiden and risks of recurrent idiopathic venous thromboembolism. Circulation, 92(10), 2800–2802.

    PubMed  CAS  Google Scholar 

  • Robertson, L., Wu, O., Langhorne, P., Twaddle, S., Clark, P., Lowe, D. O., et al. (2006). Thrombophilia in pregnancy: a systematic review. Br J Haematol, 132, 171–196.

    PubMed  CAS  Google Scholar 

  • Rosendaal, F. R. (1999). Venous thrombosis: prevalence and interaction of risk factors. Haemostasis, 29(Suppl S1), 1–9.

    PubMed  CAS  Google Scholar 

  • Rosendaal, F. R. (2005). Venous thrombosis: the role of genes, environment, and behavior. Hematology (Am Soc Hematol Educ Program), 1–12.

  • Salomon, O., Steinberg, D. M., Zivelin, A., Gitel, S., Dardik, R., Rosenberg, N., et al. (1999). Single and combined prothrombotic factors in patients with idiopathic venous thromboembolism: prevalence and risk assessment. Arterioscler Thromb Vasc Biol, 19(3), 511–518.

    PubMed  CAS  Google Scholar 

  • Samama, M. M., Dahl, O. E., Quinlan, D. J., Mismetti, P., & Rosencher, N. (2003). Quantification of risk factors for venous thromboembolism: a preliminary study for the development of a risk assessment tool. Haematologica, 88(12), 1410–1421.

    PubMed  Google Scholar 

  • Saukko, P. M., Richards, S., Shepherd, M. H., Campbell, J. (2006). Are genetic tests exceptional? Lessons from a qualitative study on thrombophilia. Social Science & Medicine (in press).

  • Schambeck, C. M., Schwender, S., Haubitz, I., Geisen, U. E., Grossmann, R. E., & Keller, F. (1997). Selective screening for the Factor V Leiden mutation: is it advisable prior to the prescription of oral contraceptives? Thromb Haemost, 78(6), 1480–1483.

    PubMed  CAS  Google Scholar 

  • Seligsohn, U., & Lubetsky, A. (2001). Genetic susceptibility to venous thrombosis. N Engl J Med, 344(16), 1222–1231.

    PubMed  CAS  Google Scholar 

  • Seligsohn, U., & Zivelin, A. (1997). Thrombophilia as a multigenic disorder. Thromb Haemost, 78(1), 297–301.

    PubMed  CAS  Google Scholar 

  • Simioni, P., Prandoni, P., Burlina, A., Tormene, D., Sardella, C., Ferrari, et al. (1996). Hyperhomocysteinemia and deep-vein thrombosis. A case-control study. Thromb Haemost, 76(6), 883–886.

    PubMed  CAS  Google Scholar 

  • Simioni, P., Prandoni, P., Lensing, A. W., Scudeller, A., Sardella, C., Prins, M. H., et al. (1997). The risk of recurrent venous thromboembolism in patients with an Arg506–>Gln mutation in the gene for factor V (factor V Leiden). N Engl J Med, 336(6), 399–403.

    PubMed  CAS  Google Scholar 

  • Spector, E. B., Grody, W. W., Matteson, C. J., Palomaki, G. E., Bellissimo, D. B., Wolff, D. J., et al. (2005). Technical standards and guidelines: venous thromboembolism (Factor V Leiden and prothrombin 20210G >A testing): a disease-specific supplement to the standards and guidelines for clinical genetics laboratories. Genet Med, 7(6), 444–453.

    Article  PubMed  Google Scholar 

  • Stark, J. E., & Kilzer, W. J. (2004). Venous thromboembolic prophylaxis in hospitalized medical patients. Ann Pharmacother, 38(1), 36–40.

    PubMed  Google Scholar 

  • Tait, R. C., Walker, I. D., Davidson, J. F., Islam, S. I., & Mitchell, R. (1990). Antithrombin III activity in healthy blood donors: age and sex related changes and prevalence of asymptomatic deficiency. Br J Haematol, 75(1), 141–142.

    PubMed  CAS  Google Scholar 

  • Tait, R. C., Walker, I. D., Reitsma, P. H., Islam, S. I., McCall, F., Poort, et al. (1995). Prevalence of protein C deficiency in the healthy population. Thromb Haemost, 73(1), 87–93.

    PubMed  CAS  Google Scholar 

  • Tal, J., Schliamser, L. M., Leibovitz, Z., Ohel, G., & Attias, D. (1999). A possible role for activated protein C resistance in patients with first and second trimester pregnancy failure. Hum Reprod, 14(6), 1624–1627.

    PubMed  CAS  Google Scholar 

  • Toole J. F., Malinow, M. R., Chambless, L. E., Spense, J. D., Pettigrew L. C., Howard, V. J., et al. (2004). Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction and death. JAMA, (291), 565–575.

    PubMed  CAS  Google Scholar 

  • van Korlaar, I. M., Vossen, C. Y., Rosendaal, F. R., Bovill, E. G., Cushman, M., Naud, S., et al. (2004). The impact of venous thrombosis on quality of life. Thromb Res, 114(1), 11–18.

    PubMed  CAS  Google Scholar 

  • van Korlaar, I. M., Vossen, C. Y., Rosendaal, F. R., Bovill, E. G., Naud, S., Cameron, L. D., et al. (2005). Attitudes toward genetic testing for thrombophilia in asymptomatic members of a large family with inherited protein C deficiency. J Thromb Haemost, 3(11), 2437–2444.

    PubMed  CAS  Google Scholar 

  • Vandenbroucke, J. P., Koster, T., Briet, E., Reitsma, P. H., Bertina, R. M., & Rosendaal, F. R. (1994). Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet, 344(8935), 1453–1457.

    PubMed  CAS  Google Scholar 

  • Varga, E., Sturm, A., Misita, C., & Moll, S. (2004). Homocysteine and MTHFR mutations: relation to thrombosis and coronary artery disease. Circulation, 111, e289–e293.

    Google Scholar 

  • Wu, O., Robertson, L., Twaddle, S., Lowe, G., Clark, P., Walker, I., et al. (2005). Screening for thrombophilia in high-risk situations: a meta-analysis and cost-effectiveness analysis. Br J Haematol, 131(1), 80–90.

    PubMed  Google Scholar 

  • Wu, O., Robertson, L., Twaddle, S., Lowe, G. D. O., Clark, P., Greaves, M., et al. (2006). Screening for thrombophilia in high-risk situations: Systemic review and cost-effectiveness analysis. The thrombosis risk and economic assessment of thrombophilia screening (TREATS) study. Health Technol Assess, 10(11), 1–110.

    PubMed  CAS  Google Scholar 

  • Younis, J. S. (2000). Thrombophilia and recurrent fetal loss–related? Fertil Steril, 73(3), 652–654.

    PubMed  CAS  Google Scholar 

  • Zoller, B., Berntsdotter, A., Garcia de Frutos, P., & Dahlback, B. (1995). Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S. Blood, 85(12), 3518–3523.

    PubMed  CAS  Google Scholar 

  • Zuber, M., Toulon, P., Marnet, L., & Mas, J. L. (1996). Factor V Leiden mutation in cerebral venous thrombosis. Stroke, 27(10), 1721–1723.

    PubMed  CAS  Google Scholar 

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ACKNOWLEDGMENTS

The author would like to acknowledge Rob Pilarski, MS, CGC and the Editors of the Journal of Genetic Counseling for recognizing the need for a review article on this topic. The author would also like to thank Stephan Moll, MD, Matthew Bower, MS, CGC and Amy Sturm MS, CGC for their critical review of this manuscript.

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  1. Department of Internal Medicine, The Ohio State University, Columbus, OH, USA

    Elizabeth Varga

  2. Division of Molecular & Human Genetics, Columbus Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USA

    Elizabeth Varga

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Correspondence to Elizabeth Varga.

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Varga, E. Inherited Thrombophilia: Key Points for Genetic Counseling. J Genet Counsel 16, 261–277 (2007). https://doi.org/10.1007/s10897-006-9069-9

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  • DOI: https://doi.org/10.1007/s10897-006-9069-9

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