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Review Article| Volume 30, ISSUE 3, P747-760, September 2010

Prenatal Screening for Thrombophilias: Indications and Controversies

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      References

        • Brenner B.
        Thrombophilia and adverse pregnancy outcome.
        Obstet Gynecol Clin North Am. 2006; 33 (ix): 443-456
        • Barbour L.A.
        ACOG educational bulletin. Thromboembolism in pregnancy. Number 234, March 1997. American College of Obstetricians and Gynecologists.
        Int J Gynaecol Obstet. 1997; 57: 209-218
        • Creasy R.K.
        • Resnik R.
        • Iams J.D.
        Creasy and Resnik's maternal-fetal medicine: principles and practice.
        6th edition. Saunders/Elsevier, Philadelphia2009
        • Hellgren M.
        Hemostasis during normal pregnancy and puerperium.
        Semin Thromb Hemost. 2003; 29: 125-130
      1. Haemostasis and Thrombosis Task Force, British Committee for Standards in Haematology. Investigation and management of heritable thrombophilia.
        Br J Haematol. 2001; 114: 512-528
        • Marik P.E.
        • Plante L.A.
        Venous thromboembolic disease and pregnancy.
        N Engl J Med. 2008; 359: 2025-2033
        • Greer I.A.
        Thrombosis in pregnancy: maternal and fetal issues.
        Lancet. 1999; 353: 1258-1265
        • Rosendaal F.R.
        Venous thrombosis: a multicausal disease.
        Lancet. 1999; 353: 1167-1173
        • Lockwood C.J.
        Inherited thrombophilias in pregnant patients: detection and treatment paradigm.
        Obstet Gynecol. 2002; 99: 333-341
        • Gerhardt A.
        • Scharf R.E.
        • Beckmann M.W.
        • et al.
        Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium.
        N Engl J Med. 2000; 342: 374-380
        • Poort S.R.
        • Rosendaal F.R.
        • Reitsma P.H.
        • et al.
        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: 3698-3703
        • Kierkegaard A.
        Incidence and diagnosis of deep vein thrombosis associated with pregnancy.
        Acta Obstet Gynecol Scand. 1983; 62: 239-243
        • Girling J.
        • de Swiet M.
        Inherited thrombophilia and pregnancy.
        Curr Opin Obstet Gynecol. 1998; 10: 135-144
        • Lane D.A.
        • Bayston T.
        • Olds R.J.
        • et al.
        Antithrombin mutation database: 2nd (1997) update. For the Plasma Coagulation Inhibitors Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis.
        Thromb Haemost. 1997; 77: 197-211
        • Frosst P.
        • Blom H.J.
        • Milos R.
        • et al.
        A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase.
        Nat Genet. 1995; 10: 111-113
        • Morelli V.M.
        • Lourenco D.M.
        • D'Almeida V.
        • et al.
        Hyperhomocysteinemia increases the risk of venous thrombosis independent of the C677 T mutation of the methylenetetrahydrofolate reductase gene in selected Brazilian patients.
        Blood Coagul Fibrinolysis. 2002; 13: 271-275
        • Miletich J.
        • Sherman L.
        • Broze Jr., G.
        Absence of thrombosis in subjects with heterozygous protein C deficiency.
        N Engl J Med. 1987; 317: 991-996
        • Tait R.C.
        • Walker I.D.
        • Reitsma P.H.
        • et al.
        Prevalence of protein C deficiency in the healthy population.
        Thromb Haemost. 1995; 73: 87-93
        • Foster D.C.
        • Yoshitake S.
        • Davie E.W.
        The nucleotide sequence of the gene for human protein C.
        Proc Natl Acad Sci U S A. 1985; 82: 4673-4677
        • Plutzky J.
        • Hoskins J.A.
        • Long G.L.
        • et al.
        Evolution and organization of the human protein C gene.
        Proc Natl Acad Sci U S A. 1986; 83: 546-550
        • Clouse L.H.
        • Comp P.C.
        The regulation of hemostasis: the protein C system.
        N Engl J Med. 1986; 314: 1298-1304
        • Dykes A.C.
        • Walker I.D.
        • McMahon A.D.
        • et al.
        A study of protein S antigen levels in 3788 healthy volunteers: influence of age, sex and hormone use, and estimate for prevalence of deficiency state.
        Br J Haematol. 2001; 113: 636-641
        • Ploos van Amstel J.K.
        • van der Zanden A.L.
        • Bakker E.
        • et al.
        Two genes homologous with human protein S cDNA are located on chromosome 3.
        Thromb Haemost. 1987; 58: 982-987
        • Schmidel D.K.
        • Tatro A.V.
        • Phelps L.G.
        • et al.
        Organization of the human protein S genes.
        Biochemistry. 1990; 29: 7845-7852
        • Esmon C.T.
        The protein C anticoagulant pathway.
        Arterioscler Thromb. 1992; 12: 135-145
        • Schwarz H.P.
        • Fischer M.
        • Hopmeier P.
        • et al.
        Plasma protein S deficiency in familial thrombotic disease.
        Blood. 1984; 64: 1297-1300
        • Broekmans A.W.
        • Bertina R.M.
        • Reinalda-Poot J.
        • et al.
        Hereditary protein S deficiency and venous thrombo-embolism. A study in three Dutch families.
        Thromb Haemost. 1985; 53: 273-277
        • Holmes Z.R.
        • Bertina R.M.
        • Reitsma P.H.
        Characterization of a large chromosomal deletion in the PROS1 gene of a patient with protein S deficiency type I using long PCR.
        Br J Haematol. 1996; 92: 986-991
        • Zoller B.
        • Berntsdotter A.
        • Garcia de Frutos P.
        • et al.
        Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S.
        Blood. 1995; 85: 3518-3523
        • MacCallum P.K.
        • Cooper J.A.
        • Martin J.
        • et al.
        Associations of protein C and protein S with serum lipid concentrations.
        Br J Haematol. 1998; 102: 609-615
        • Esplin S.M.
        ACOG Practice Bulletin #68: antiphospholipid syndrome.
        Obstet Gynecol. 2005; 106: 1113-1121
        • Miyakis S.
        • Lockshin M.D.
        • Atsumi T.
        • et al.
        International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).
        J Thromb Haemost. 2006; 4: 295-306
        • Passam F.
        • Krilis S.
        Laboratory tests for the Antiphospholipid syndrome: current concepts.
        Pathology. 2004; 36: 129-138
        • Roubey R.A.
        Autoantibodies to phospholipid-binding plasma proteins: a new view of lupus anticoagulants and other “antiphospholipid” autoantibodies.
        Blood. 1994; 84: 2854-2867
        • Heit J.A.
        • Kobbervig C.E.
        • James A.H.
        • et al.
        Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study.
        Ann Intern Med. 2005; 143: 697-706
        • James A.H.
        • Jamison M.G.
        • Brancazio L.R.
        • et al.
        Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality.
        Am J Obstet Gynecol. 2006; 194: 1311-1315
        • Eby C.
        Antiphospholipid syndrome review.
        Clin Lab Med. 2009; 29: 305-319
        • Cervera R.
        • Piette J.C.
        • Font J.
        • et al.
        Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients.
        Arthritis Rheum. 2002; 46: 1019-1027
        • Silver R.M.
        • Draper M.L.
        • Scott J.R.
        • et al.
        Clinical consequences of antiphospholipid antibodies: an historic cohort study.
        Obstet Gynecol. 1994; 83: 372-377
        • Zotz R.B.
        • Gerhardt A.
        • Scharf R.E.
        Inherited thrombophilia and gestational venous thromboembolism.
        Best Pract Res Clin Haematol. 2003; 16: 243-259
        • Seligsohn U.
        • Lubetsky A.
        Genetic susceptibility to venous thrombosis.
        N Engl J Med. 2001; 344: 1222-1231
        • Robertson L.
        • Wu O.
        • Langhorne P.
        • et al.
        Thrombophilia in pregnancy: a systematic review.
        Br J Haematol. 2006; 132: 171-196
        • Kang S.S.
        • Zhou J.
        • Wong P.W.
        • et al.
        Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase.
        Am J Hum Genet. 1988; 43: 414-421
        • 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: 292-299
        • McColl M.D.
        • Ellison J.
        • Reid F.
        • et al.
        Prothrombin 20210 G–>A, MTHFR C677 T mutations in women with venous thromboembolism associated with pregnancy.
        BJOG. 2000; 107: 565-569
        • Domagala T.B.
        • Adamek L.
        • Nizankowska E.
        • et al.
        Mutations C677 T 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: 423-431
        • den Heijer M.
        • Willems H.P.
        • Blom H.J.
        • et al.
        Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: a randomized, placebo-controlled, double-blind trial.
        Blood. 2007; 109: 139-144
        • Friederich P.W.
        • Sanson B.J.
        • Simioni P.
        • et al.
        Frequency of pregnancy-related venous thromboembolism in anticoagulant factor-deficient women: implications for prophylaxis.
        Ann Intern Med. 1996; 125: 955-960
        • Vila P.
        • Hernandez M.C.
        • Lopez-Fernandez M.F.
        • et al.
        Prevalence, follow-up and clinical significance of the anticardiolipin antibodies in normal subjects.
        Thromb Haemost. 1994; 72: 209-213
        • Oshiro B.T.
        • Silver R.M.
        • Scott J.R.
        • et al.
        Antiphospholipid antibodies and fetal death.
        Obstet Gynecol. 1996; 87: 489-493
        • Rai R.
        • Cohen H.
        • Dave M.
        • et al.
        Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies).
        BMJ. 1997; 314: 253-257
        • Kutteh W.H.
        Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone.
        Am J Obstet Gynecol. 1996; 174: 1584-1589
        • Farquharson R.G.
        • Quenby S.
        • Greaves M.
        Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment.
        Obstet Gynecol. 2002; 100: 408-413
        • Alfirevic Z.
        • Roberts D.
        • Martlew V.
        How strong is the association between maternal thrombophilia and adverse pregnancy outcome? A systematic review.
        Eur J Obstet Gynecol Reprod Biol. 2002; 101: 6-14
        • Rey E.
        • Kahn S.R.
        • David M.
        • et al.
        Thrombophilic disorders and fetal loss: a meta-analysis.
        Lancet. 2003; 361: 901-908
        • Kovalevsky G.
        • Gracia C.R.
        • Berlin J.A.
        • et al.
        Evaluation of the association between hereditary thrombophilias and recurrent pregnancy loss: a meta-analysis.
        Arch Intern Med. 2004; 164: 558-563
        • Lissalde-Lavigne G.
        • Fabbro-Peray P.
        • Cochery-Nouvellon E.
        • et al.
        Factor V Leiden and prothrombin G20210A polymorphisms as risk factors for miscarriage during a first intended pregnancy: the matched case-control ‘NOHA first’ study.
        J Thromb Haemost. 2005; 3: 2178-2184
        • Roque H.
        • Paidas M.J.
        • Funai E.F.
        • et al.
        Maternal thrombophilias are not associated with early pregnancy loss.
        Thromb Haemost. 2004; 91: 290-295
        • Gris J.C.
        • Mercier E.
        • Quere I.
        • et al.
        Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder.
        Blood. 2004; 103: 3695-3699
        • Branch D.W.
        • Silver R.M.
        • Blackwell J.L.
        • et al.
        Outcome of treated pregnancies in women with antiphospholipid syndrome: an update of the Utah experience.
        Obstet Gynecol. 1992; 80: 614-620
        • Lima F.
        • Khamashta M.A.
        • Buchanan N.M.
        • et al.
        A study of sixty pregnancies in patients with the antiphospholipid syndrome.
        Clin Exp Rheumatol. 1996; 14: 131-136
        • Yasuda M.
        • Takakuwa K.
        • Tokunaga A.
        • et al.
        Prospective studies of the association between anticardiolipin antibody and outcome of pregnancy.
        Obstet Gynecol. 1995; 86: 555-559
        • Lynch A.
        • Marlar R.
        • Murphy J.
        • et al.
        Antiphospholipid antibodies in predicting adverse pregnancy outcome. A prospective study.
        Ann Intern Med. 1994; 120: 470-475
        • Pattison N.S.
        • Chamley L.W.
        • McKay E.J.
        • et al.
        Antiphospholipid antibodies in pregnancy: prevalence and clinical associations.
        Br J Obstet Gynaecol. 1993; 100: 909-913
        • Facco F.
        • You W.
        • Grobman W.
        Genetic thrombophilias and intrauterine growth restriction: a meta-analysis.
        Obstet Gynecol. 2009; 113: 1206-1216
        • Fretts R.C.
        ACOG Practice Bulletin No. 102: Management of stillbirth.
        Obstet Gynecol. 2009; 113: 748-761
        • James A.H.
        Prevention and management of venous thromboembolism in pregnancy.
        Am J Med. 2007; 120: S26-S34
        • Ginsberg J.S.
        • Kowalchuk G.
        • Hirsh J.
        • et al.
        Heparin therapy during pregnancy. Risks to the fetus and mother.
        Arch Intern Med. 1989; 149: 2233-2236
        • Lepercq J.
        • Conard J.
        • Borel-Derlon A.
        • et al.
        Venous thromboembolism during pregnancy: a retrospective study of enoxaparin safety in 624 pregnancies.
        BJOG. 2001; 108: 1134-1140
        • Brill-Edwards P.
        • Ginsberg J.S.
        • Gent M.
        • et al.
        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. 2000; 343: 1439-1444
        • Bates S.M.
        • Greer I.A.
        • Pabinger I.
        • et al.
        Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition).
        Chest. 2008; 133: 844S-886S