Download PDF
Semin Thromb Hemost 2003; 29(2): 171-174
DOI: 10.1055/s-2003-38832
Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Coagulation Factor Deficiencies and Pregnancy Loss

Aida Inbal1 , Laszlo Muszbek2
  • 1Associate Professor, and Acting Director, Institute of Thrombosis and Hemostasis, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel
  • 2Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center, University of Debrecen, Hungary
Further Information

Publication History

Publication Date:
23 April 2003 (online)

    Permissions and Reprints

ABSTRACT

Of all the coagulation factor deficiencies, only deficiency of factor XIII (FXIII) and fibrinogen are associated with pregnancy loss. FXIII deficiency and a complete or partial deficiency of fibrinogen are associated with bleeding since childhood, impaired wound repair, and recurrent spontaneous abortions. Both FXIII and fibrinogen play an essential role in placental implantation and maintenance of pregnancy. The causes of miscarriages in FXIII or fibrinogen-deficient women is discussed and an appropriate treatment advocated.

KEYWORDS

Factor XIII deficiency - afibrinogenemia - miscarriages

REFERENCES

  • 1 Schwartz M L, Pizzo S V, McKee P A. Human factor XIII from plasma and platelets.  J Biol Chem . 1973;  248 1395-1407
    PubMedSearch in Google Scholar
  • 2 Muszbek L, Yee V C, Hevessy Z. Blood coagulation factor XIII: structure and function.  Thromb Res . 1999;  94 271-305
    CrossrefPubMedSearch in Google Scholar
  • 3 Fisher S, Rikover M, Naor S. Factor 13 deficiency with severe hemorrhagic diathesis.  Blood . 1966;  28 34-39
    PubMedSearch in Google Scholar
  • 4 Anwar T, Miloszewski K. Factor XIII deficiency.  Br J Haematol . 1999;  107 468-484
    CrossrefPubMedSearch in Google Scholar
  • 5 Ádány R, Muszbek L. Immunohistochemical detection of Factor XIII subunit a in histiocytes of human uterus.  Histochemistry . 1989;  91 169-174
    CrossrefPubMedSearch in Google Scholar
  • 6 Asahina T, Kobayashi T, Okada Y. et al . Studies on the role of adhesive proteins in maintaining pregnancy.  Horm Res . 1998;  50(Suppl 2) 37-45
    CrossrefPubMedSearch in Google Scholar
  • 7 Ádány R, Glukhova M, Kabakov A Y. et al . Characterization of connective tissue cells containing factor XIII subunit a.  J Clin Pathol . 1988;  41 49-56
    PubMedSearch in Google Scholar
  • 8 Kappelmayer J, Bacsko G, Kelemen E. et al . Onset and distribution of factor XIII-containing cells in the mesenchyme of chorionic villi during early phase of human placentation.  Placenta . 1994;  15 613-623
    PubMedSearch in Google Scholar
  • 9 Muszbek L, Ádány R, Kávai M. et al . Monocytes of patients congenitally deficient in plasma factor XIII lack factor XIII subunit A antigen and transglutaminase activity.  Thromb Haemost . 1988;  59 231-235
    PubMedSearch in Google Scholar
  • 10 Rodeghiero F, Castaman G C, Di Bona E. et al . Successful pregnancy in a woman with congenital factor XIII deficiency treated with substitute therapy.  Blut . 1987;  55 45-48
    PubMedSearch in Google Scholar
  • 11 Boda Z, Pfliegler G, Muszbek L. et al . Congenital factor XIII deficiency with multiple benign breast tumors and successful pregnancy with substitutive therapy.  Haemostasis . 1989;  19 348-352
    PubMedSearch in Google Scholar
  • 12 Kobayashi T, Terao T, Kojima T. et al . Congenital factor XIII deficiency with treatment of factor XIII concentrate and normal vaginal delivery.  Gynecol Obstet Invest . 1990;  29 235-238
    PubMedSearch in Google Scholar
  • 13 Burrows R F, Ray J G, Burrows E A. Bleeding risk and reproductive capacity among patients with factor XIII deficiency: a case presentation and review of the literature.  Obstet Gynecol Survey . 2000;  55 103-8
    PubMedSearch in Google Scholar
  • 14 Wartiovaara J, Leivo I, Virtanen I. et al . Cell surface and extracellular matrix glycoprotein fibronectin. Expression in embryogenesis and in teratocarcinoma differentiation.  Ann NY Acad Sci . 1978;  312 132-141
    PubMedSearch in Google Scholar
  • 15 Vicovac L, Aplin J D. Epithelial-mesenchymal transition during trophoblast differentiation.  Acta Anat . 1966;  156 202-216
    PubMedSearch in Google Scholar
  • 16 Kobayashi T, Asahina T, Okada Y. et al . Studies on the localization of adhesive proteins associated with the development of extravillous cytotrophoblast.  Trophoblast Res . 1999;  13 35-53
    PubMedSearch in Google Scholar
  • 17 Asahina T, Kobayashi T, Okada Y. et al . Maternal blood coagulation factor XIII is associated with the development of cytotrophoblastic shell.  Placenta . 2000;  21 388-393
    CrossrefPubMedSearch in Google Scholar
  • 18 Brackmann H H, Egbring R, Feister A. et al . Pharmacokinetics and tolerability of factor XIII concentrates prepared from human placenta or plasma: A crossover randomized trial.  Thromb Haemost . 1995;  74 622-625
    PubMedSearch in Google Scholar
  • 19 Mikkola H, Muszbek L, Laiho E. et al . Molecular mechanism of a mild phenotype in coagulation factor XIII (FXIII) deficiency: a splicing mutation permitting partial correct splicing of FXIII A-subunit mRNA.  Blood . 1997;  89 1279-1287
    PubMedSearch in Google Scholar
  • 20 Hayano Y, Ima N, Kasaraura T. Studies on the physiologic changes of blood coagulation factor XIII during pregnancy and their significance.  Acta Obstet Gynaecol Jpn . 1982;  34 469-477
    PubMedSearch in Google Scholar
  • 21 Nossel H L, Lanzkowsky P, Levy S. et al . A study of coagulation levels in women during labor and their newborn infants.  Thromb Diath Haemorrhag . 1966;  16 185-197
    PubMedSearch in Google Scholar
  • 22 Biland L, Duckert F. Coagulation factors in the newborn and his mother.  Thromb Diath Haemorrhag . 1973;  29 644-651
    PubMedSearch in Google Scholar
  • 23 Coopland A, Alkjaersig N, Fletcher A P. Reduction in plasma factor XIII (fibrin stabilizing factor) concentration during pregnancy.  L Lab Clin Med . 1969;  73 144-153
    PubMedSearch in Google Scholar
  • 24 van Wersch W J, Vooijs M E, Ubachs J M. Coagulation factor XIII in pregnant smokers and non-smokers.  Int J Clin Lab Res . 1997;  27 68-71
    PubMedSearch in Google Scholar
  • 25 Stirling Y, Woolf L, North W RS. et al . Haemostasis in normal pregnancy.  Thromb Haemost . 1984;  52 176-182
    PubMedSearch in Google Scholar
  • 26 Ogasawara M S, Aoki K, Katano K. et al . Factor XII but not protein C, protein S, antithrombin III, or factor VIII is a predictor of recurrent miscarriage.  Fertil Steril . 2001;  75 916-919
    CrossrefPubMedSearch in Google Scholar
  • 27 Galanakis D K. Fibrinogen anomalies and disease. A clinical update.  Hematol Oncol Clin N Am . 1992;  6 1171-1187
    PubMedSearch in Google Scholar
  • 28 Doolittle R F. The molecular biology of fibrin. In: Stamatoyannopoulos GS, Nienhuis AW, Majerus PW, Varmus H, eds. The Molecular Basis of Blood Diseases Philadelphia, PA: WB Saunders 1994: 701-723
    Search in Google Scholar
  • 29 Bennett J S. Integrin structure and function in hemostasis and thrombosis.  Ann NY Acad Sci . 1991;  614 214-228
    PubMedSearch in Google Scholar
  • 30 Mosesson M W. Dysfibrinogenemia and thrombosis.  Semin Thromb Hemost . 1999;  25 311-319
    Thieme ConnectPubMedSearch in Google Scholar
  • 31 Ridgway H J, Brennan S O, Faed J M, George P M. Fibrinogen Otago: a major α chain truncation associated with severe hypofibrinogenaemia and recurrent miscarriage.  Br J Haematol . 1997;  98 632-639
    CrossrefPubMedSearch in Google Scholar
  • 32 Suh T T, Holmback K, Jensen N. et al . Resolution of spontaneous bleeding events but failure of pregnancy in fibrinogen-deficient mice.  Genes Dev . 1995;  9 2020-2033
    CrossrefPubMedSearch in Google Scholar
  • 33 Inamoto Y, Terao T. First report of a case of congenital afibrinogenemia with successful delivery.  Am J Obstet Gynecol . 1985;  153 803-804
    CrossrefPubMedSearch in Google Scholar
  • 34 Gilabert J, Reganon E, Vila V. et al . Congenital hypofibrinogenemia and pregnancy: obstetric and hematological management.  Gynecol Obstet Invest . 1987;  24 271-276
    PubMedSearch in Google Scholar
  • 35 Ingram G IC, McBrien D J, Spencer H. Fatal pulmonary embolus in congenital fibrinopenia. Report of two cases.  Acta Hematol . 1966;  35 56-62
    PubMedSearch in Google Scholar
  • 36 MacKinnon H H, Fekete J F. Congenital afibrinogenemia: vascular changes and multiple thromboses induced by fibrinogen infusions and contraceptive medication.  J Can Med Assoc . 1971;  140 597-599
    PubMedSearch in Google Scholar
  • 37 Beck E A. Congenital abnormalities of fibrinogen.  Clin Haematol . 1979;  8 169-181
    PubMedSearch in Google Scholar