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Inherited Bleeding Disorders in Pregnancy: Rare Coagulation Factor Defects

  • Flora Peyvandi
  • Marzia Menegatti
  • Simona Maria Siboni
Chapter

Abstract

Inherited deficiencies of plasma proteins involved in blood coagulation generally lead to lifelong bleeding disorders. Rare bleeding disorders (RBDs), discussed in this chapter, represent 3–5 % of all the inherited coagulation deficiencies, with prevalence ranging from approximately 1:500,000 to 1:2,000,000 in the general population. Patients affected by bleeding disorders present a wide spectrum of clinical symptoms that vary from a mild or moderate bleeding tendency to significant episodes. Women with inherited bleeding disorders are particularly disadvantaged since, in addition to suffering from general bleeding symptoms, they are also at risk of bleeding complications from regular haemostatic challenges during menstruation, pregnancy and childbirth. Moreover, such disorders pose important problems for affected women due to their reduced quality of life caused by limitations in activities and work, and alteration of their reproductive life. Management of these women is difficult because of considerable inter-individual variation. Furthermore, reliable information on clinical management is scarce, with only a few long-term prospective studies of large cohorts providing evidence to guide diagnosis and treatment.

Keywords

Bleeding Disorder Placental Abruption Factor Deficiency Spontaneous Miscarriage Bleeding History 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Mannucci PM, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood. 2004;104:1243–52.PubMedCrossRefGoogle Scholar
  2. 2.
    Tuddenham EGD, Cooper DN. The molecular genetics of haemostasis and its inherited disorders. Oxford: Oxford Medical Publications; 1994 (Oxford Monography on Medical Genetics No. 25).Google Scholar
  3. 3.
    Peyvandi F, Palla R, Menegatti M, Mannucci PM. Introduction: rare bleeding disorders: general aspects of clinical features, diagnosis, and management. Semin Thromb Hemost. 2009;35:349–55.PubMedCrossRefGoogle Scholar
  4. 4.
    Peyvandi F, Palla R, Menegatti M. European Registry of Rare Bleeding Disorders. Hematology Education: the education programme for the annual congress of the European Hematology Association 2010;4:43.Google Scholar
  5. 5.
    Sun WY, Witte DP, Degen JL, et al. Prothrombin deficiency results in embryonic and neonatal lethality in mice. Proc Natl Acad Sci USA. 1998;95:7597–602.PubMedCrossRefGoogle Scholar
  6. 6.
    Lak M, Sharifian R, Peyvandi F, Mannucci PM. Symptoms of inherited factor V deficiency in 35 Iranian patients. Br J Haematol. 1998;103:1067–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Lak M, Keihani M, Elahi F, et al. Bleeding and thrombosis in 55 patients with inherited afibrinogenaemia. Br J Haematol. 1999;107:204–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Lak M, Peyvandi F, Ali Sharifian A, et al. Pattern of symptoms in 93 Iranian patients with severe factor XIII deficiency. J Thromb Haemost. 2003;1:1852–3.PubMedCrossRefGoogle Scholar
  9. 9.
    Peyvandi F, Mannucci PM, Asti D, et al. Clinical manifestations in 28 Italian and Iranian patients with severe factor VII deficiency. Haemophilia. 1997;3:242–6.CrossRefGoogle Scholar
  10. 10.
    Peyvandi F, Mannucci PM, Lak M, et al. Congenital factor X deficiency: spectrum of bleeding symptoms in 32 Iranian patients. Br J Haematol. 1998;102:626–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Peyvandi F, Tuddenham EG, Akhtari AM, et al. Bleeding symptoms in 27 Iranian patients with the combined deficiency of factor V and factor VIII. Br J Haematol. 1998;100:773–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Peyvandi F, Lak M, Mannucci PM. Factor XI deficiency in Iranians: its clinical manifestations in comparison with those of classic hemophilia. Haematologica. 2002;87:512–4.PubMedGoogle Scholar
  13. 13.
    Acharya SS, Coughlin A, Dimichele DM. Rare Bleeding Disorder Registry: deficiencies of factors II, V, VII, X, XIII, fibrinogen and dysfibrinogenemias. J Thromb Haemost. 2004;2:248–56.PubMedCrossRefGoogle Scholar
  14. 14.
    James AH. More than menorrhagia: a review of the obstetric and gynaecological manifestations of bleeding disorders. Haemophilia. 2005;11:295–307.PubMedCrossRefGoogle Scholar
  15. 15.
    Kadir RA, Economides DL, Sabin CA, et al. Frequency of inherited bleeding disorders in women with menorrhagia. Lancet. 1998;351:485–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Stirling Y, Woolf L, North WR, et al. Haemostasis in normal pregnancy. Thromb Haemost. 1984;52:176–82.PubMedGoogle Scholar
  17. 17.
    Sanchez-Luceros A, Meschengieser SS, Marchese C, et al. Factor VIII and von Willebrand factor changes during normal pregnancy and puerperium. Blood Coagul Fibrinolysis. 2003;14:647–51.PubMedCrossRefGoogle Scholar
  18. 18.
    Wickstrom K, Edelstam G, Lowbeer CH, et al. Reference intervals for plasma levels of fibronectin, von Willebrand factor, free protein S and antithrombin during third-trimester pregnancy. Scand J Clin Lab Invest. 2004;64:31–40.PubMedCrossRefGoogle Scholar
  19. 19.
    Bremme KA. Haemostatic changes in pregnancy. Best Pract Res Clin Haematol. 2003;16:153–68.PubMedCrossRefGoogle Scholar
  20. 20.
    Hellgren M, Blomback M. Studies on blood coagulation and fibrinolysis in pregnancy, during delivery and in the puerperium. Normal condition. Gynecol Obstet Invest. 1981;12:141–54.PubMedCrossRefGoogle Scholar
  21. 21.
    Bremme K, Ostlund E, Almqvist I, et al. Enhanced thrombin generation and fibrinolytic activity in normal pregnancy and the puerperium. Obstet Gynecol. 1992;80:132–7.PubMedGoogle Scholar
  22. 22.
    Sie P, Caron C, Azam J, et al. Reassessment of von Willebrand factor (VWF), VWF propeptide, factor VIII:C and plasminogen activator inhibitors 1 and 2 during normal pregnancy. Br J Haematol. 2003;121:897–903.PubMedCrossRefGoogle Scholar
  23. 23.
    Salomon O, Steinberg DM, Tamarin I, et al. Plasma replacement therapy during labor is not mandatory for women with severe factor XI deficiency. Blood Coagul Fibrinolysis. 2005;16:37–41.PubMedCrossRefGoogle Scholar
  24. 24.
    Myers B, Pavord S, Kean L, et al. Pregnancy outcome in Factor XI deficiency: incidence of miscarriage, antenatal and postnatal haemorrhage in 33 women with Factor XI deficiency. BJOG. 2007;114:643–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Everett C. Incidence and outcome of bleeding before the 20th week of pregnancy: prospective study from general practice. BMJ. 1997;315:32–4.PubMedCrossRefGoogle Scholar
  26. 26.
    Nybo Andersen AM, Wohlfahrt J, Christens P, et al. Maternal age and fetal loss: population based register linkage study. BMJ. 2000;320:1708–12.PubMedCrossRefGoogle Scholar
  27. 27.
    Evron S, Anteby SO, Brzezinsky A, et al. Congenital afibrinogenemia and recurrent early abortion: a case report. Eur J Obstet Gynecol Reprod Biol. 1985;19:307–11.PubMedCrossRefGoogle Scholar
  28. 28.
    Kobayashi T, Kanayama N, Tokunaga N, et al. Prenatal and peripartum management of congenital afibrinogenaemia. Br J Haematol. 2000;109:364–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Inbal A, Kenet G. Pregnancy and surgical procedures in patients with factor XIII deficiency. Biomed Prog. 2003;16:69–71.Google Scholar
  30. 30.
    Burrows RF, Ray JG, Burrows EA. Bleeding risk and reproductive capacity among patients with factor XIII deficiency: a case presentation and review of the ­literature. Obstet Gynecol Surv. 2000;55:103–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Haverkate F, Samama M. Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on Fibrinogen. Thromb Haemost. 1995;73:151–61.PubMedGoogle Scholar
  32. 32.
    Catanzarite VA, Novotny WF, Cousins LM, Schneider JM. Pregnancies in a patient with congenital absence of prothrombin activity: case report. Am J Perinatol. 1997;14:135–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Kulkarni AA, Lee CA, Kadir RA. Pregnancy in women with congenital factor VII deficiency. Haemo­philia. 2006;12:413–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Kumar M, Mehta P. Congenital coagulopathies and pregnancy: report of four pregnancies in a factor X-deficient woman. Am J Hematol. 1994;46:241–4.PubMedCrossRefGoogle Scholar
  35. 35.
    Larrain C. Congenital blood coagulation factor X deficiency. Successful result of the use prothrombin concentrated complex in the control of caesarean section hemorrhage in 2 pregnancies. Rev Med Chil. 1994;122:1178–83.PubMedGoogle Scholar
  36. 36.
    Romagnolo C, Burati S, Ciaffoni S, et al. Severe factor X deficiency in pregnancy: case report and review of the literature. Haemophilia. 2004;10:665–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Siboni SM, Spreafico M, Calò L, Maino A, Santagostino E, Federici AB, Peyvandi F. Gynaeco­logical and obstetrical problems in women with different bleeding disorders. Haemophilia. 2009;15:1291–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Greer IA, Lowe GD, Walker JJ, Forbes CD. Haemorrhagic problems in obstetrics and gynaecology in patients with congenital coagulopathies. Br J Obstet Gynaecol. 1991;98:909–18.PubMedCrossRefGoogle Scholar
  39. 39.
    Inamoto Y, Terao T. First report of case of congenital afibrinogenemia with successful delivery. Am J Obstet Gynecol. 1985;153:803–4.PubMedGoogle Scholar
  40. 40.
    Ross M. Placental and fetal physiology. In: Gabbe S, Niebyl J, Simpson J, editors. Obstetrics: normal and problem pregnancies. New York: Churchill Living­stone; 2002. p. 37–62.Google Scholar
  41. 41.
    Benedetti T. Obstetrical hemorrhage. In: Gabbe S, Niebyl J, Simpson J, editors. Obstetrics: normal and problem pregnancies. New York: Churchill Living­stone; 2002. p. 503–38.Google Scholar
  42. 42.
    Fadel HE, Krauss JS. Factor VII deficiency and pregnancy. Obstet Gynecol. 1989;73:453–4.PubMedGoogle Scholar
  43. 43.
    Strickland DM, Galey WT, Hauth JC. Hypofibrino­genemia as a cause of delayed postpartum ­hemorrhage. Am J Obstet Gynecol. 1982;143:230–1.PubMedGoogle Scholar
  44. 44.
    Robertson LE, Wasserstrum N, Banez E, et al. Hereditary factor VII deficiency in pregnancy: peripartum treatment with factor VII concentrate. Am J Hematol. 1992;40:38–41.PubMedCrossRefGoogle Scholar
  45. 45.
    Goodwin TM. Congenital hypofibrinogenemia in pregnancy. Obstet Gynecol Surv. 1989;44:157–61.PubMedCrossRefGoogle Scholar
  46. 46.
    Noia G, De Carolis S, De Stefano V, et al. Factor V deficiency in pregnancy complicated by Rh immunization and placenta previa. A case report and review of the literature. Acta Obstet Gynecol Scand. 1997;76:890–2.PubMedCrossRefGoogle Scholar
  47. 47.
    Rizk DE, Castella A, Shaheen H, Deb P. Factor VII deficiency detected in pregnancy: a case report. Am J Perinatol. 1999;16:223–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Girolami A, Lazzarin M, Scarpa R, Brunetti A. Further studies on the abnormal factor X (factor X Friuli) coagulation disorder: a report of another family. Blood. 1971;37:534–41.PubMedGoogle Scholar
  49. 49.
    Ichinose A, Asahina T, Kobayashi T. Congenital blood coagulation factor XIII deficiency and perinatal management. Curr Drug Targets. 2005;6:541–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Edwards A, Ellwood DA. Ultrasonographic evaluation of the postpartum uterus. Ultrasound Obstet Gynecol. 2000;16:640–3.PubMedCrossRefGoogle Scholar
  51. 51.
    Visness CM, Kennedy KI, Ramos R. The duration and character of postpartum bleeding among breast-feeding women. Obstet Gynecol. 1997;89:159–63.PubMedCrossRefGoogle Scholar
  52. 52.
    Dahlman T, Hellgren M, Blombäck M. Changes in blood coagulation and fibrinolysis in the normal puerperium. Gynecol Obstet Invest. 1985;20:37–44.PubMedCrossRefGoogle Scholar
  53. 53.
    Lawrie AS, Kitchen S, Purdy G, et al. Assessment of actin FS and actin FSL sensitivity to specific clotting factor deficiencies. Clin Lab Haematol. 1998;20:179–86.PubMedCrossRefGoogle Scholar
  54. 54.
    Turi DC, Peerschke EI. Sensitivity of three activated partial thromboplastin time reagents to coagulation factor deficiencies. Am J Clin Pathol. 1986;85:43–9.PubMedGoogle Scholar
  55. 55.
    Jennings I, Kitchen S, Woods TAL, Preston FE. Problems relating to the laboratory diagnosis of factor XIII deficiency: a UK NEQAS study. J Thromb Haemost. 2003;1:2603–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Fickenscher K, Aab A, Stuber W. A Photometric assay for blood coagulation factor XIII. Thromb Haemost. 1991;65:535–40.PubMedGoogle Scholar
  57. 57.
    Katona E, Haramura G, Karpati L, et al. A simple, quick one-step ELISA assay for the determination of complex plasma factor XIII (A2B2). Thromb Haemost. 2000;83:268–73.PubMedGoogle Scholar
  58. 58.
    Nichols WC, Seligsohn U, Zivelin A, et al. Mutations in the ER-Golgi intermediate compartment protein ERGIC-53 cause combined deficiency of coagulation factors V and VIII. Cell. 1998;93:61–70.PubMedCrossRefGoogle Scholar
  59. 59.
    Zhang B, Cunningham MA, Nichols WC, et al. Bleeding due to disruption of a cargo-specific ER-to-Golgi ­transport complex. Nat Genet. 2003;34:220–5.PubMedCrossRefGoogle Scholar
  60. 60.
    Mousallem M, Spronk HM, Sacy R, et al. Congenital combined deficiencies of all vitamin K-dependent coagulation factors. Thromb Haemost. 2001;86:1334–6.PubMedGoogle Scholar
  61. 61.
    Rost S, Fregin A, Ivaskevicius V, et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004;427:537–41.PubMedCrossRefGoogle Scholar
  62. 62.
    Bolton-Maggs PH, Perry DJ, Chalmers EA, et al. The rare coagulation disorders – review with guidelines for management from the United Kingdom Haemophilia Centre Doctors’ Organisation. Haemophilia. 2004;10:593–628.PubMedCrossRefGoogle Scholar
  63. 63.
    Trehan AK, Fergusson IL. Congenital afibrinogenaemia and successful pregnancy outcome (Case report). Br J Obstet Gynaecol. 1991;98:722–4.PubMedCrossRefGoogle Scholar
  64. 64.
    Frenkel E, Duksin C, Herman A, Sherman DJ. Congenital hypofibrinogenemia in pregnancy: report of two cases and review of the literature. Obstet Gynecol Surv. 2004;59:775–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Dupuy E, Soria C, Molho P, et al. Embolized ischemic lesions of toes in an afibrinogenemic patient: possible relevance to in vivo circulating thrombin. Thromb Res. 2001;102:211–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Braun MW, Triplett DA. Case report: factor VII deficiency in an obstetrical patient. J Indiana State Med Assoc. 1979;72:900–2.PubMedGoogle Scholar
  67. 67.
    Eskandari N, Feldman N, Greenspoon JS. Factor VII deficiency in pregnancy treated with recombinant ­factor VIIa. Obstet Gynecol. 2002;99:935–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Jimenez-Yuste V, Villar A, Morado M, et al. Continuous infusion of recombinant activated factor VII during caesarean section delivery in a patient with congenital factor VII deficiency. Haemophilia. 2000;6:588–90.PubMedCrossRefGoogle Scholar
  69. 69.
    Konje JC, Murphy P, de Chazal R, et al. Severe factor X deficiency and successful pregnancy. Br J Obstet Gynaecol. 1994;101:910–1.PubMedCrossRefGoogle Scholar
  70. 70.
    Bofill JA, Young RA, Perry Jr KG. Successful pregnancy in a woman with severe factor X deficiency. Obstet Gynecol. 1996;88:723.PubMedCrossRefGoogle Scholar
  71. 71.
    Rodeghiero F, Castaman GC, Di Bona E, et al. Successful pregnancy in a woman with congenital factor XIII deficiency treated with substitutive therapy. Report of a second case. Blut. 1987;55:45–8.PubMedCrossRefGoogle Scholar
  72. 72.
    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;29:235–8.PubMedCrossRefGoogle Scholar
  73. 73.
    Asahina T, Kobayashi T, Takeuchi K, Kanayama N. Congenital blood coagulation factor XIII deficiency and successful deliveries: a review of the literature. Obstet Gynecol Surv. 2007;62:255–60.PubMedCrossRefGoogle Scholar
  74. 74.
    Kadir R, Chi C, Bolton-Maggs P. Pregnancy and rare bleeding disorders. Haemophilia. 2009;15:990–1005.PubMedCrossRefGoogle Scholar
  75. 75.
    Todd T, Perry DJ. A review of long-term prophylaxis in the rare inherited coagulation factor deficiencies. Haemophilia. 2010;16:569–83.PubMedGoogle Scholar

Copyright information

© Springer-Verlag London 2012

Authors and Affiliations

  • Flora Peyvandi
    • 1
  • Marzia Menegatti
    • 1
  • Simona Maria Siboni
    • 1
  1. 1.A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Cá Granda Ospedale Maggiore Policlinico, and Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano and Luigi Villa FoundationMilanItaly

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