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2 - Recurrent miscarriage syndrome and infertility caused by blood coagulation protein/platelet defects

Published online by Cambridge University Press:  01 February 2010

By
Rodger L. Bick M.D., Ph.D., F.A.C.P.
Edited by
Rodger L. Bick ,
Eugene P. Frenkel ,
William F. Baker  and
Ravi Sarode
Rodger L. Bick M.D., Ph.D., F.A.C.P.
Affiliation:
Clinical Professor of Medicine and Pathology, University of Texas Southwestern Medical Center; Director: Dallas Thrombosis Hemostasis and Vascular Medicine Clinical Center, Dallas, Texas, USA
Rodger L. Bick
Affiliation:
University of Texas Southwestern Medical Center, Dallas
Eugene P. Frenkel
Affiliation:
University of Texas Southwestern Medical Center, Dallas
William F. Baker
Affiliation:
University of California, Los Angeles
Ravi Sarode
Affiliation:
University of Texas Southwestern Medical Center, Dallas
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Summary

Introduction

Recurrent miscarriage syndrome (RMS) is a common obstetrical problem, affecting over 500,000 women in the USA per year; infertility although less well defined in the population is also a common clinical problem.

Recurrent miscarriage, based upon literature available and our experience is generally due to well defined defects as follows: about 7% are secondary to chromosomal abnormalities, about 10% are due to anatomical abnormalities, about 15% appear due to hormonal abnormalities (progesterone, estrogens, diabetes or thyroid disease), about 6% cannot be explained and the remainder, about 55 to 62%, are due to blood coagulation protein/platelet defects. The approximate prevalence of causes of RMS/infertility are summarized in Figure 2.1. This is in contrast to first time miscarriage, which in about 90% of cases, is due to a chromosomal defect and may effect up to 25 percent of first time pregnancies.

Blood coagulation protein/platelet defects

Recurrent miscarriage syndrome (RMS) due to blood protein or platelet defects may come about through two mechanisms, those disorders associated with a hemorrhagic tendency or those defects associated with a thrombotic tendency. Hemorrhagic (bleeding) defects associated with RMS are very rare, while thrombotic or hypercoagulable/thrombophilic defects are extremely common. The hemorrhagic defects associated with fetal wastage syndrome presumably lead to inadequate fibrin formation, thus precluding adequate implantation of the fertilized ovum into the uterus.

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Hematological Complications in Obstetrics, Pregnancy, and Gynecology , pp. 55 - 74
Publisher: Cambridge University Press
Print publication year: 2006

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References

Bick, R. L., Recurrent miscarriage syndrome and infertility caused by blood coagulation protein or platelet defects. Hematology Oncology Clin. North America, 14: 1117, 2000.CrossRefGoogle ScholarPubMed
Bick, R. L., Laughlin, H. R., Cohen, B., et al. Fetal wastage syndrome due to blood protein/platelet defects: results of prevalence studies and treatment outcome with low-dose heparin and low-dose aspirin. Clin. Appl. Thrombosis Hemostasis, 1: 286, 1995.CrossRefGoogle Scholar
Duckert, F.The fibrin stabilizing factor, Factor XIII. Blut, 26: 177, 1973.CrossRefGoogle ScholarPubMed
Dossenbach-Glaninger, A., Trotsenburg, M., Dossenbach, , Oberkanins, C., et al. Plasminogen activator inhibitor 1 4G/5G polymorphism and coagulation factor XIII Val34Leu polymorphism: impaired fibrinolysis and early pregnancy loss. Clin. Chem., 49: 1081, 2003.CrossRefGoogle ScholarPubMed
Muszbek, I. A.Coagulation factor deficiencies and pregnancy loss. Sem. Thromb. Hemost., 29: 171, 2003.CrossRefGoogle Scholar
Kumar, M. and Mehta, P.Congenital coagulopathies and pregnancy: report of four pregnancies in a Factor X-deficient woman. Am. J. Hematol., 46: 241, 1994.CrossRefGoogle Scholar
Valnicek, S., Vacl, J., Mrazova, M., et al. Hemotherapeutic safeguarding of induced abortion in inborn proconvertin insufficiency (hemagglutination Factor VII) using exchange plasmapheresis. Zentralblatt fur Gynakologie, 94: 931, 1972.Google ScholarPubMed
Nelson, D. B., Ness, R. B., Grisso, J. A. and Cushman, M.Influence of hemostatic factors on spontaneous abortionAm. J. Perinatol., 4: 195, 2001.CrossRefGoogle Scholar
Slunsky, R.Personal experiences with the antifibrinolytic PAMBA in obstetrics and gynecology. Zentralblatt für Gynakologie, 92: 364, 1970.Google ScholarPubMed
Owen, C. A., Henriksen, R. A., McDuffie, F. C., et al. Prothrombin quick: a newly identified dysprothrombinemiaMayo Clinic Proceedings, 53: 29, 1978.Google ScholarPubMed
Pauer, H. U., Burfeind, P., Kostering, H., et al. Factor XII deficiency is strongly associated with primary recurrent abortions. Fertil Steril. Sep., 80: 590, 2003.CrossRefGoogle ScholarPubMed
Jones, D. W., Gallimore, M. J. and Winter, M.Antibodies to factor XII: a possible predictive marker for recurrent foetal loss. Immunobiology, 207: 43, 2003.CrossRefGoogle ScholarPubMed
Sugi, T. and Makino, T.Antiphospholipid antibodies and kininogens in pathologic pregnancies: a review. Am. J. Reprod. Immunol., 47: 283, 2002.CrossRefGoogle ScholarPubMed
Iinuma, Y., Sugiura-Ogasawara, M., Makino, A., et al. Coagulation factor XII activity, but not an associated common genetic polymorphism (46C/T), is linked to recurrent miscarriage. Fertil. Steril., 77: 353–6, 2002.CrossRefGoogle Scholar
Yamada, H., Kato, E. H., Ebina, Y., et al. Factor XII deficiency in women with recurrent miscarriage. Gynecol. Obstet. Invest., 49: 80, 2000.CrossRefGoogle ScholarPubMed
Evron, S., Anteby, S. O., Brzezinsky, A., et al. Congenital afibrinogenemia and recurrent early abortion. European J. Obstet. Gynecol. Reproductive Biol., 19: 307, 1985.CrossRefGoogle ScholarPubMed
Mammen, E. F.Congenital abnormalities of the fibrinogen molecule. Seminars Thrombosis Hemostasis, 1: 184, 1974.CrossRefGoogle Scholar
Bick, R. L., Baker, W. F.Antiphospholipid syndrome and thrombosis. Seminars Thrombosis Hemostasis, 25: 333, 1999.CrossRefGoogle ScholarPubMed
Bick, R. L.The antiphospholipid thrombosis syndromes: a common mutlidisciplinary medical problem. Clin. Appl. Thrombosis Hemostasis, 3: 270, 1997.CrossRefGoogle Scholar
Scott, J. R., Rote, N. S. and Branch, D. W.Immunological aspects of recurrent abortion and fetal death. Obstet. Gynecol., 70: 645, 1987.Google Scholar
Schved, J. F., Gris, J. C., Neveu, S., et al. Factor XII congenital deficiency and early spontaneous abortion. Fertility and Sterility, 52: 335, 1989.CrossRefGoogle ScholarPubMed
Klein, M., Rosen, A., Kyrle, P., et al. Obstetrical management of dysfibrinogenemia with increased thrombophilia. Geburtshilfe und Frauenheilkunde, 52: 442, 1992.CrossRefGoogle ScholarPubMed
Barkagan, Z. S. and Belykh, S. I.Protein C deficiency and the multi-thrombotic syndrome associated with pregnancy and abortion. Gematologia I Transfuziologiia, 37: 35, 1992.Google ScholarPubMed
Hellgren, M., Tengborn, L. and Abildgaard, U.Pregnancy in women with congenital antithrombin III deficiency: experience of treatment with heparin and antithrombin. Gynecologic and Obstetric Investigation, 14: 127, 1982.CrossRefGoogle ScholarPubMed
Simioni, P., Lazzaro, A. R., Coser, E., et al. Hereditary heparin cofactor II deficiency and thrombosis: report of six patients belonging to two separate cohorts. Blood Coagulation and Fibrinolysis, 1: 351, 1990.CrossRefGoogle Scholar
Satoh, A., Suzuki, K., Takayama, E., et al. Detection of anti-annexin IV and V antibodies in patients with antiphospholipid syndrome and systemic lupus erythematosus. J. Rheum., 26: 1715, 1999.Google ScholarPubMed
Gris, J., Neveu, S., Mares, P., et al. Plasma fibrinolytic activators and their inhibitors in women suffering from early recurrent abortion of unknown etiology. J. Lab. Clin. Med., 125: 606, 1993.Google Scholar
Glueck, C. J., Wang, P., Fontaine, R. N., et al. Plasminogen activator inhibitor activity: an independent risk factor for the high miscarriage rate during pregnancy in women with polycystic ovary syndrome. Metabolism: Clinical & Experimental, 48: 1589, 1999.CrossRefGoogle ScholarPubMed
Khamashta, M. A.Management of thrombosis and pregnancy loss in the antiphospholipid syndrome. Lupus, 7(Suppl. 2): S162–5, 1998.CrossRefGoogle ScholarPubMed
Amengual, O., Atsumi, T., Khamashta, M. A., et al. Advances in antiphospholipid (Hughes') syndrome. Annals of the Academy of Medicine, Singapore, 27: 61, 1998.Google ScholarPubMed
Bick, R. L.Antiphospholipid thrombosis syndromes: etiology, pathophysiology, diagnosis and managment. International J. Hematology, 65: 193, 1997.CrossRefGoogle Scholar
Bick, R. L., Baker, W. F.The Antiphospholipid and Thrombosis Syndromes. Medical Clinics North America, 78: 667, 1994.CrossRefGoogle ScholarPubMed
Bick, R. L., Arun, B., Frenkel, E. P.Antiphospholipid thrombosis syndromes. Haemostasis, 29: 100, 1999.Google ScholarPubMed
Festin, M. R., Limson, G. M., Maruo, T.Autoimmune causes of recurrent pregnancy loss. Kobe Journal of Medical Sciences, 43: 143, 1997.Google ScholarPubMed
Roussev, R. G., Kaider, B. D., Price, D. E., et al. Laboratory evaluation of women experiencing reproductive failure. Am. J. Reproductive Immunology (Copenhagen), 35: 415, 1996.CrossRefGoogle ScholarPubMed
Oshiro, B. T., Silver, R. M., Scott, J. R., et al. Antiphospholipid antibodies and fetal death. Obstetrics & Gynecology, 87: 489, 1996.CrossRefGoogle ScholarPubMed
Granger, K. A. and Farquharson, R. G.Obstetric outcome in antiphospholipid syndrome. Lupus, 6: 509, 1997.CrossRefGoogle ScholarPubMed
Borrelli, A. L., Brillante, M., Borzacchiello, C., et al. Hemocoagulative pathology and immunological recurrent abortion. Clinical & Experimental Obstetrics & Gynecology, 24: 39, 1997.Google ScholarPubMed
Hellan, M., Kuhnel, E., Speiser, W., et al. Familial lupus anticoagulant: a case report and review of the literature. Blood Coagulation & Fibrinolysis, 9: 195, 1998.CrossRefGoogle ScholarPubMed
Ogasawara, M., Aoki, K., Matsuura, E., et al. Anti beta-2-glycoprotein I antibodies and lupus anticoagulant in patients with recurrent pregnancy loss: prevalence and clinical significance. Lupus, 5: 587, 1996.CrossRefGoogle ScholarPubMed
Zangari, M., Lockwood, C. J., Scher, J., et al. Prothrombin activation fragment (F1.2) is increased in pregnant patients with antiphospholipid antibodies. Thromb. Res., 85: 177, 1997.CrossRefGoogle ScholarPubMed
Aznar, J.Factor V Leiden and antibodies against phospholipids and protein S in a young woman with recurrent thromboses and abortion. Haematologica, 84: 80, 1999.Google Scholar
Aznar, J., Villa, P., Espana, F., et al. Activated protein C resistance phenotype in patients with antiphospholipid antibodies. J. Lab. & Clin. Med., 130: 202, 1997.CrossRefGoogle ScholarPubMed
Schultz, D. R.Antiphospholipid antibodies: basic immunology and assays. Seminars in Arthritis & Rheumatism, 26: 724, 1997.CrossRefGoogle ScholarPubMed
Amengual, O., Atsumi, T., Khamashta, M. A., et al. The role of the tissue factor pathway in the hypercoagulable state in patients with the antiphospholipid syndrome. Thrombosis & Haemostasis, 79: 276, 1998.CrossRefGoogle ScholarPubMed
Martini, A. and Ravelli, A.The clinical significance of antiphospholipid antibodies. Annals of Medicine, 29: 159, 1997.CrossRefGoogle ScholarPubMed
Bussen, S. S. and Steck, T.Thyroid antibodies and their relation to antithrombin antibodies, anticardiolipin antibodies and lupus anticoagulant in women with recurrent spontaneous abortions (antithyroid, anticardiolipin and antithrombin autoantibodies and lupus anticoagulant in habitual aborters). European J. Obs. Gyn. Repro. Biol., 74: 139, 1997.CrossRefGoogle Scholar
Rand, J. H. and Wu, X. X.Antibody-mediated disruption of the annexin-V antithrombotic shield: a new mechanism for thrombosis in the antiphospholipid syndrome. Thrombosis & Haemostasis, 82: 649, 1999.Google ScholarPubMed
Rand, J. H., Wu, X. X., Andree, H. A., et al. Antiphospholipid antibodies accelerate plasma coagulation by inhibiting annexin-V binding to phospholipids: a “lupus procoagulant” phenomenon. Blood, 92: 1652, 1998.Google ScholarPubMed
Rauch, J.Lupus anticoagulant antibodies: recognition of phospholipid-binding protein complexes. Lupus, 7(Suppl. 2): S29, 1998.CrossRefGoogle ScholarPubMed
Rote, N. S., Vogt, E., DeVere, G., et al. The role of placental trophoblast in the pathophysiology of the antiphospholipid antibody syndrome. Am. J. Repro. Immunol. (Copenhagen), 39: 125, 1998.CrossRefGoogle ScholarPubMed
Vogt, E., Ng, A. K. and Rote, N. S.Antiphosphatidylserine antibody removes annexin-V and facilitates the binding of prothrombin at the surface of a choriocarcinoma model of trophoblast differentiation. Am. J. Obs. Gyn., 177: 964, 1997.CrossRefGoogle ScholarPubMed
Lakasing, L., Campa, J. S., Poston, R., et al. Normal expression of tissue factor, thrombomodulin, and annexin V in placentas from women with antiphospholipid syndrome. Am. J. Obs. Gyn., 181: 180, 1999.CrossRefGoogle ScholarPubMed
Siaka, C., Lambert, M., Caron, C., et al. Low prevalence of anti-annexin V antibodies in antiphospholipid syndrome with fetal loss. Revue de Medecine Interne, 20: 762, 1999.CrossRefGoogle ScholarPubMed
Kaburaki, J., Kuwana, M., Yamamoto, M., et al. Clinical significance of anti-annexin V antibodies in patients with systemic lupus erythematosus. Am. J. Hematol., 54: 209, 1997.3.0.CO;2-#>CrossRefGoogle ScholarPubMed
Eschwege, V., Peynaud-Debayle, E., Wolf, M., et al. Prevalence of antiphospholipid-related antibodies in unselected patients with history of venous thrombosis. Blood Coagulation & Fibrinolysis, 9: 429, 1998.CrossRefGoogle ScholarPubMed
Silver, R. M., Pierangeli, S. S., Edwin, S. S., et al. Pathogenic antibodies in women with obstetric features of antiphospholipid syndrome who have negative test results for lupus anticoagulant and anticardiolipin antibodies. Am. J. Obs. Gyn., 176: 628, 1997.CrossRefGoogle ScholarPubMed
Branch, D. W., Silver, R., Pierangeli, S., et al. Antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin antibodies in women with recurrent pregnancy loss, fertile controls, and antiphospholipid syndrome. Obs. Gyn., 89: 549, 1997.Google ScholarPubMed
Gris, J. C., Ripart-Neveu, S., Maugard, C., et al. Respective evaluation of the prevalence of haemostasis abnormalities in unexplained primary early recurrent miscarriages. The Nimes Obstetricians and Haematologists (NOHA) Study. Thrombosis & Haemostasis, 77: 1096, 1997.Google ScholarPubMed
Tal, J., Schliamser, L. M., Leibovitz, Z., et al. A possible role for activated protein C resistance in patients with first and second trimester pregnancy failure. Human Reproduction, 14: 1624, 1999.CrossRefGoogle ScholarPubMed
Kutteh, W. H., Park, V. M. and Deitcher, S. R.Hypercoagulable state mutation analysis in white patients with early first-trimester recurrent pregnancy loss. Fertility & Sterility., 71: 1048, 1998.CrossRefGoogle Scholar
Dhalback, B.Activated Protein C resistence and thrombosis: Molecular mechanisms of hypercoagulable state due to FVR506Q mutation. Seminars Thrombosis Hemostasis, 25: 273, 1999.CrossRefGoogle Scholar
Brenner, B., Mandel, H., Lanir, N., et al. Activated Protein C resistance can be associated with recurrent fetal loss. Brit. J. Haematology, 97: 551, 1997.CrossRefGoogle ScholarPubMed
Bokarewa, M. I., Bremme, K., Blomback, M.Arg 506-Gln mutation in factor V and risk of thrombosis during pregnancy. Brit. J. Haematology, 92: 473, 1996.CrossRefGoogle Scholar
Rai, R., Regan, L., Hadley, E., et al. Second-trimester pregnancy loss is associated with activated C resistance. Brit. J. Haematology, 92: 489, 1996.CrossRefGoogle ScholarPubMed
Grandone, E., Margaglione, M., Colaizzo, D., et al. Factor V Leiden mutation is associated with repeated and recurrent unexplained fetal losses. Thromb. Haemostasis, 77: 822, 1997.Google ScholarPubMed
Ridker, P. M., Miletich, J. P., Buring, J. E., et al. Factor V Leiden mutation as a risk factor for recurrent pregnancy loss. Ann. Internal Medicine, 128: 1000, 1998.CrossRefGoogle ScholarPubMed
Poort, S., Rosendaal, F., Reitsma, P., 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 thrombosisBlood, 88: 3698, 1996.Google ScholarPubMed
Brenner, B., Sarig, G., Weiner, Z., et al. Thrombophilic polymorphisms are common in women with fetal loss without apparent cause. Thrombosis & Haemostasis, 82: 6, 1999.Google ScholarPubMed
Toschi, V., Motta, A., Costelli, C., et al. High prevalence of antiphosphatidylinositol antibodies in young patients with cerebral ischemia of undetermined causeStroke, 29: 1759, 1998.CrossRefGoogle ScholarPubMed
Sher, G., Feinman, M., Zouves, C., et al. High fecundity rates following in-vitro fertilization and embryo transfer in antiphospholipid antibody seropositive women treated with heparin and aspirin. Human Reproduction, 9: 2278, 1994.CrossRefGoogle ScholarPubMed
Rosove, M. H., Tabsh, K., Wasserstrum, N., et al. Heparin therapy for pregnant women with lupus anticoagulant or anticardiolipin antibodies. Obstetrics Gynecology, 75: 630, 1990.Google ScholarPubMed
Brown, H. L.Antiphospholipid antibodies and recurrent pregnancy loss. Clinical Obstetrics Gynecology, 34: 17, 1991.CrossRefGoogle ScholarPubMed
Perino, A., Barba, G., Cimino, C., et al. Immunological problems in the recurrent abortion syndrome. Acta Eurtopaea Fertilitatis, 20: 199, 1989.Google ScholarPubMed
Many, A., Pauzner, R., Carp, H., et al. Treatment of patients with antiphospholipid antibodies during pregnancy. American J. Reproductive Immunology, 28: 216, 1992.CrossRefGoogle ScholarPubMed
Lubbe, W. F. and Liggins, G. C.Role of lupus anticoagulant and autoimmunity in recurrent fetal loss. Seminars Reproductive Endocrinology, 6: 181, 1988.CrossRefGoogle Scholar
Lin, Q.Investigation of the association between autoantibodies and recurrent abortions. Chinese J. Obstetrics Gynecology, 28: 674, 1993.Google ScholarPubMed
Cowchuck, F. S., Reece, E. A., Balaban, D., et al. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment. American J. Obstetrics Gynecology, 166: 1318, 1992.CrossRefGoogle Scholar
Landy, H. J., Kessler, C., Kelly, W. K., et al. Obstetric performance in patients with the lupus anticoagulant and/or anticardiolipin antibodies. American J. Perinatology, 9: 146, 1992.CrossRefGoogle ScholarPubMed
Semprini, A. E., Vucetich, A., Garbo, S., et al. Effect of prednisone and heparin treatment in 14 patients with poor reproductive efficiency related to lupus anticoagulant. Fetal Therapy, 4(Suppl. 1): 73, 1989.CrossRefGoogle ScholarPubMed
Kutteh, W. H.Heparin plus aspirin (Hep + ASA) is superior to aspirin alone (ASA) for the treatment of recurrent pregnancy loss (RPL) associated with antiphospholipid antibodies (APA). Proceedings: American College Obstetricians & Gynecologists, 1994 (abstract).Google Scholar
Parke, A. The role of IVIG in the management of patients with antiphospholipid antibodies and recurrent pregnancy losses. IVIG Therapy Today. Ballow, M., ed. Totowa, N. J., Humana Press, Inc., 1992, p. 105.CrossRefGoogle Scholar

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