Journal of Genetic Counseling

, Volume 16, Issue 3, pp 261–277

Inherited Thrombophilia: Key Points for Genetic Counseling

Professional Development Paper

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.


thrombophilia factor V Leiden prothrombin genetic counseling risk assessment venous thromboembolism recurrent pregnancy loss 


  1. 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
  2. ACOG Practice Bulletin #68: Antiphospholipid syndrome. (2005). Obstet Gynecol, 106(5 Pt 1), 1113–1121.Google Scholar
  3. 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.PubMedGoogle Scholar
  4. 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.PubMedGoogle Scholar
  5. 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.PubMedGoogle Scholar
  6. 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.PubMedGoogle Scholar
  7. 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.PubMedGoogle Scholar
  8. Barbour, L. A. (2001). ACOG practice bulletin. Thrombembolism in pregnancy. Int J Gynaecol Obstet, 75(2), 203–212.PubMedGoogle Scholar
  9. 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
  10. Bauer, K. A. (2001). The thrombophilias: well-defined risk factors with uncertain therapeutic implications. Ann Intern Med, 135(5), 367–373.PubMedGoogle Scholar
  11. 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.PubMedGoogle Scholar
  12. 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.PubMedGoogle Scholar
  13. 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.PubMedGoogle Scholar
  14. 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
  15. 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.PubMedGoogle Scholar
  16. 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.PubMedGoogle Scholar
  17. 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.PubMedGoogle Scholar
  18. 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.PubMedGoogle Scholar
  19. 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.PubMedGoogle Scholar
  20. College of American Pathologists Consensus Conference XXXVI: Diagnostic Issues in Thrombophilia. (2002). Arch Pathol Lab Med, 126(11), 1277–1433.Google Scholar
  21. 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
  22. 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.PubMedGoogle Scholar
  23. Cushman, M. (2005). Inhertied risk factors for venous thrombosis. Hematology (Am Soc Hematol Educ Program) 452–457.Google Scholar
  24. 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.PubMedGoogle Scholar
  25. 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.PubMedGoogle Scholar
  26. den Heijer, M., & Keijzer, M. B. (2001). Hyperhomocysteinemia as a risk factor for venous thrombosis. Clin Chem Lab Med, 39(8), 710–713.PubMedGoogle Scholar
  27. 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.PubMedGoogle Scholar
  28. Egeberg, O. (1965). Inherited Antithrombin Deficiency Causing Thrombophilia. Thromb Diath Haemorrh, 13, 516–530.PubMedGoogle Scholar
  29. 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.PubMedGoogle Scholar
  30. 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
  31. 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.PubMedGoogle Scholar
  32. FDA Updates Labeling for Ortho Evra Contraceptive Patch. FDA News, November 10, 2005, Accessed September 15, 2006.Google Scholar
  33. 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.PubMedGoogle Scholar
  34. 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.PubMedGoogle Scholar
  35. 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.PubMedGoogle Scholar
  36. 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.Google Scholar
  37. Goldhaber, S., & Fanikos, J. (2004). Prevention of deep vein thrombosis and pulmonary embolism. Circulation, 110, e445–e447.PubMedGoogle Scholar
  38. Gompel, A., Levy, D. P., & Conard, J. (2002). Ovarian hyperstimulation and thrombosis. Women's Issues Thrombosis and Haemostasis, London: Martin Dunitz pp. 143–150Google Scholar
  39. Greaves, M., & Watson, H. G. (2003). Laboratory testing for prothrombotic states: Clinical utility. Curr Hematol Rep, 2(5), 429–434.PubMedGoogle Scholar
  40. Greer, I. A. (2005). Venous thromboembolism and anticoagulant therapy in pregnancy. Gend Med, 2(Suppl A), S10–17.PubMedGoogle Scholar
  41. 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.PubMedGoogle Scholar
  42. 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.PubMedGoogle Scholar
  43. 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.PubMedGoogle Scholar
  44. 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
  45. 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
  46. Heit, J. A. (2006). The epidemiology of venous thromboembolism in the community: Implications for prevention and management. J Thromb Thrombolysis, 21(1), 23–29.PubMedGoogle Scholar
  47. 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.PubMedGoogle Scholar
  48. 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.PubMedGoogle Scholar
  49. 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.PubMedGoogle Scholar
  50. Hellmann, E., & Moll, S. (2004). Prothrombin 20210 mutation (Factor II Mutation). Circulation, 110, e15–e18.Google Scholar
  51. 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.PubMedGoogle Scholar
  52. Hirsh, J., Piovella, F., & Pini, M. (1989). Congenital antithrombin III deficiency. Incidence and clinical features. Am J Med, 87(3B), 34S–38S.PubMedGoogle Scholar
  53. James, A., Abel, D., & Brancazio, L. (2005). Anticoagulants in Pregnancy. Obstet Gynecol Survey, 61(1), 59–69.Google Scholar
  54. Kamphuisen, P. W., & Rosendaal, F. R. (2004). Thrombophilia screening: A matter of debate. Neth J Med, 62(6), 180–187.PubMedGoogle Scholar
  55. 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.PubMedGoogle Scholar
  56. Kearon, C. (1999). Initial treatment of venous thromboembolism. Thromb Haemost, 82(2), 887–891.PubMedGoogle Scholar
  57. 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.PubMedGoogle Scholar
  58. 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.PubMedGoogle Scholar
  59. Kottke-Marchant, K. (2002). Genetic polymorphisms associated with venous and arterial thrombosis: An overview. Arch Pathol Lab Med, 126(3), 295–304.PubMedGoogle Scholar
  60. 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.PubMedGoogle Scholar
  61. Kottke-Marchant, K., & Duncan, A. (2002). Antithrombin deficiency: issues in laboratory diagnosis. Arch Pathol Lab Med, 126(11), 1326–1336.PubMedGoogle Scholar
  62. 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.PubMedGoogle Scholar
  63. 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.PubMedGoogle Scholar
  64. 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.PubMedGoogle Scholar
  65. 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.PubMedGoogle Scholar
  66. 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.PubMedGoogle Scholar
  67. 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.PubMedGoogle Scholar
  68. Lockwood, C. J. (2002). Inherited thrombophilias in pregnant patients: detection and treatment paradigm. Obstet Gynecol, 99(2), 333–341.PubMedGoogle Scholar
  69. Makris, M., Rosendaal, F. R., & Preston, F. E. (1997). Familial thrombophilia: genetic risk factors and management. J Intern Med Suppl, 740, 9–15.PubMedGoogle Scholar
  70. 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.PubMedGoogle Scholar
  71. Martinelli, I. (2001). Risk factors in venous thromboembolism. Thromb Haemost, 86(1), 395–403.PubMedGoogle Scholar
  72. Martinelli, I. (2003). Pros and cons of thrombophilia testing: pros. J Thromb Haemost, 1(3), 410–411.PubMedGoogle Scholar
  73. 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.PubMedGoogle Scholar
  74. 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
  75. 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.PubMedGoogle Scholar
  76. 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.PubMedCrossRefGoogle Scholar
  77. Misita, C., & Moll, S. (2005). Antiphospholipid antibodies. Circulation, 112, e39–e44.PubMedGoogle Scholar
  78. Moll, S. (2006). Thrombophilias–practical implications and testing caveats. J Thromb Thrombolysis, 21(1), 7–15.PubMedGoogle Scholar
  79. Nicolaides, A. N. (2005). Thrombophilia and venous thromboembolism. international consensus statement: Guidelines according to scientific evidence. Int Angiol, 24(1), 1–26.PubMedGoogle Scholar
  80. Ornstein, D. L., & Cushman M. (2003). Factor V Leiden. Circulation 107, e94–e97.PubMedGoogle Scholar
  81. Ozcan, T., & Copel, J. (2002). Deciphering the role of thrombophilias in recurrent miscarriage. Contemporary OB/GYN, 6, 122–132.Google Scholar
  82. 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.PubMedGoogle Scholar
  83. 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.PubMedGoogle Scholar
  84. 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.PubMedGoogle Scholar
  85. 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.PubMedGoogle Scholar
  86. 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.PubMedGoogle Scholar
  87. Rey, E., Kahn, S. R., David, M., & Shrier, I. (2003). Thrombophilic disorders and fetal loss: a meta-analysis. Lancet, 361(9361), 901–908.PubMedGoogle Scholar
  88. 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.PubMedGoogle Scholar
  89. 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.PubMedGoogle Scholar
  90. 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.PubMedGoogle Scholar
  91. 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.PubMedGoogle Scholar
  92. Rosendaal, F. R. (1999). Venous thrombosis: prevalence and interaction of risk factors. Haemostasis, 29(Suppl S1), 1–9.PubMedGoogle Scholar
  93. Rosendaal, F. R. (2005). Venous thrombosis: the role of genes, environment, and behavior. Hematology (Am Soc Hematol Educ Program), 1–12.Google Scholar
  94. 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.PubMedGoogle Scholar
  95. 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.PubMedGoogle Scholar
  96. 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).Google Scholar
  97. 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.PubMedGoogle Scholar
  98. Seligsohn, U., & Lubetsky, A. (2001). Genetic susceptibility to venous thrombosis. N Engl J Med, 344(16), 1222–1231.PubMedGoogle Scholar
  99. Seligsohn, U., & Zivelin, A. (1997). Thrombophilia as a multigenic disorder. Thromb Haemost, 78(1), 297–301.PubMedGoogle Scholar
  100. 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.PubMedGoogle Scholar
  101. 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.PubMedGoogle Scholar
  102. 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.PubMedCrossRefGoogle Scholar
  103. Stark, J. E., & Kilzer, W. J. (2004). Venous thromboembolic prophylaxis in hospitalized medical patients. Ann Pharmacother, 38(1), 36–40.PubMedGoogle Scholar
  104. 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.PubMedGoogle Scholar
  105. 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.PubMedGoogle Scholar
  106. 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.PubMedGoogle Scholar
  107. 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.PubMedGoogle Scholar
  108. 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.PubMedGoogle Scholar
  109. 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.PubMedGoogle Scholar
  110. 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.PubMedGoogle Scholar
  111. 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
  112. 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.PubMedGoogle Scholar
  113. 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.PubMedGoogle Scholar
  114. Younis, J. S. (2000). Thrombophilia and recurrent fetal loss–related? Fertil Steril, 73(3), 652–654.PubMedGoogle Scholar
  115. 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.PubMedGoogle Scholar
  116. Zuber, M., Toulon, P., Marnet, L., & Mas, J. L. (1996). Factor V Leiden mutation in cerebral venous thrombosis. Stroke, 27(10), 1721–1723.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Department of Internal MedicineThe Ohio State UniversityColumbusUSA
  2. 2.Division of Molecular & Human GeneticsColumbus Children’s Hospital, 700 Children’s DriveColumbusUSA

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