Inherited Bleeding Disorders in Pregnancy: Platelet Defects



Platelet function disorders (PFDs) include the severe bleeding disorders Glanzmann thrombasthenia (GT) and Bernard Soulier syndrome (BSS), and a heterogenous group of other non-severe phenotype platelet defects. GT and BSS confer significant risk of ante-partum and post-partum bleeding and may be complicated by alloimmunisation against platelet antigens, potentially causing maternal platelet refractoriness and fetal alloimmune thrombocytopenia. This chapter reviews the prevalence of bleeding in GT and BSS, and in non-severe PFDs. We describe the available therapies to prevent or treat obstetric bleeding in women with PFD and summarise current management strategies.


Platelet Transfusion Human Leucocyte Antigen Chorionic Villus Sampling Preconception Counseling Bernard Soulier Syndrome 
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  1. 1.
    Morrison R, Crawford J, MacPherson M, Heptinstall S. Platelet behaviour in normal pregnancy, pregnancy complicated by essential hypertension and pregnancy-induced hypertension. Thromb Haemost. 1985;54:607–11.PubMedGoogle Scholar
  2. 2.
    Louden KA, Broughton Pipkin F, Heptinstall S, Fox SC, Mitchell JR, Symonds EM. A longitudinal study of platelet behaviour and thromboxane production in whole blood in normal pregnancy and the puerperium. Br J Obstet Gynaecol. 1990;97:1108–14.PubMedCrossRefGoogle Scholar
  3. 3.
    Sheu JR, Hsiao G, Shen MY, Lin WY, Tzeng CR. The hyperaggregability of platelets from normal pregnancy is mediated through thromboxane A2 and cyclic AMP pathways. Clin Lab Haematol. 2002;24:121–9.PubMedGoogle Scholar
  4. 4.
    Bagamery K, Landau R, Kvell K, Graham J. Different platelet activation levels in non-pregnant, normotensive pregnant, pregnancy-induced hypertensive and pre-eclamptic women. A pilot study of flow cytometric analysis. Eur J Obstet Gynecol Reprod Biol. 2005;121:117–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Janes SL, Goodall AH. Flow cytometric detection of circulating activated platelets and platelet hyper-responsiveness in pre-eclampsia and pregnancy. Clin Sci (Lond). 1994;86:731–9.Google Scholar
  6. 6.
    Douglas JT, Shah M, Lowe GD, Belch JJ, Forbes CD, Prentice CR. Plasma fibrinopeptide A and beta-thromboglobulin in pre-eclampsia and pregnancy hypertension. Thromb Haemost. 1982;47:54–5.PubMedGoogle Scholar
  7. 7.
    Star J, Rosene K, Ferland J, DiLeone G, Hogan J, Kestin A. Flow cytometric analysis of platelet activation throughout normal gestation. Obstet Gynecol. 1997;90:562–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Harlow FH, Brown MA, Brighton TA, Smith SL, Trickett AE, Kwan YL, Davis GK. Platelet activation in the hypertensive disorders of pregnancy. Am J Obstet Gynecol. 2002;187:688–95.PubMedCrossRefGoogle Scholar
  9. 9.
    Nicolini U, Guarneri D, Gianotti GA, Campagnoli C, Crosignani PG, Gatti L. Maternal and fetal platelet activation in normal pregnancy. Obstet Gynecol. 1994;83:65–9.PubMedGoogle Scholar
  10. 10.
    Oron G, Ben-Haroush A, Hod M, Orvieto R, Bar J. Serum-soluble CD40 ligand in normal pregnancy and in preeclampsia. Obstet Gynecol. 2006;107:896–900.PubMedCrossRefGoogle Scholar
  11. 11.
    Horn EH, Cooper JA, Hardy E, Heptinstall S, Rubin PC. Longitudinal studies of platelet cyclic AMP during healthy pregnancy and pregnancies at risk of ­pre-eclampsia. Clin Sci (Lond). 1995;89:91–9.Google Scholar
  12. 12.
    Konijnenberg A, Stokkers EW, van der Post JA, Schaap MC, Boer K, Bleker OP, Sturk A. Extensive platelet activation in preeclampsia compared with normal pregnancy: enhanced expression of cell adhesion molecules. Am J Obstet Gynecol. 1997;176:461–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Halim A, Kanayama N, el Maradny E, Nakashima A, Bhuiyan AB, Khatun S, Terao T. Plasma P selectin (GMP-140) and glycocalicin are elevated in preeclampsia and eclampsia: their significances. Am J Obstet Gynecol. 1996;174:272–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Mellembakken JR, Solum NO, Ueland T, Videm V, Aukrust P. Increased concentrations of soluble CD40 ligand, RANTES and GRO-alpha in preeclampsia – possible role of platelet activation. Thromb Haemost. 2001;86:1272–6.PubMedGoogle Scholar
  15. 15.
    Norris LA, Gleeson N, Sheppard BL, Bonnar J. Whole blood platelet aggregation in moderate and severe pre-eclampsia. Br J Obstet Gynaecol. 1993;100:684–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Takeuchi T, Yoneyama Y, Suzuki S, Sawa R, Otsubo Y, Araki T. Regulation of platelet aggregation in vitro by plasma adenosine in preeclampsia. Gynecol Obstet Invest. 2001;51:36–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Ahmed Y, Sullivan MH, Elder MG. Detection of platelet desensitization in pregnancy-induced hypertension is dependent on the agonist used. Thromb Haemost. 1991;65:474–7.PubMedGoogle Scholar
  18. 18.
    Plow EF, Pesho MM, Ma Y-Q. Integrin alphaIIbBeta3. 2nd ed. Boston: Elsevier; 2007.Google Scholar
  19. 19.
    Kottke-Marchant K, Corcoran G. The laboratory diagnosis of platelet disorders. Arch Pathol Lab Med. 2002;126:133–46.PubMedGoogle Scholar
  20. 20.
    French DL. The molecular genetics of Glanzmann’s thrombasthenia. Platelets. 1998;9:5–20.PubMedCrossRefGoogle Scholar
  21. 21.
    George JN, Caen JP, Nurden AT. Glanzmann’s thrombasthenia: the spectrum of clinical disease. Blood. 1990;75:1383–95.PubMedGoogle Scholar
  22. 22.
    Markovitch O, Ellis M, Holzinger M, Goldberger S, Beyth Y. Severe juvenile vaginal bleeding due to Glanzmann’s thrombasthenia: case report and review of the literature. Am J Hematol. 1998;57:225–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Andrews RK, Berndt MC, Lopez JA. Platelets. London: Elsevier; 2007.Google Scholar
  24. 24.
    Bolton-Maggs PH, Chalmers EA, Collins PW, Harrison P, Kitchen S, Liesner RJ, Minford A, Mumford AD, Parapia LA, Perry DJ, Watson SP, Wilde JT, Williams MD. A review of inherited platelet disorders with guidelines for their management on behalf of the UKHCDO. Br J Haematol. 2006;135:603–33.PubMedCrossRefGoogle Scholar
  25. 25.
    Kunishima S, Kamiya T, Saito H. Genetic abnormalities of Bernard-Soulier syndrome. Int J Hematol. 2002;76:319–27.PubMedCrossRefGoogle Scholar
  26. 26.
    Lopez JA, Andrews RK, Afshar-Kharghan V, Berndt MC. Bernard-Soulier syndrome. Blood. 1998;91:4397–418.PubMedGoogle Scholar
  27. 27.
    Savoia A, Balduini CL, Savino M, Noris P, Del Vecchio M, Perrotta S, Belletti S. Poggi, iolascon A: autosomal dominant macrothrombocytopenia in Italy is most frequently a type of heterozygous Bernard-Soulier syndrome. Blood. 2001;97:1330–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Rao AK, Jalagadugula G, Sun L. Inherited defects in platelet signaling mechanisms. Semin Thromb Hemost. 2004;30:525–35.PubMedCrossRefGoogle Scholar
  29. 29.
    Nurden P, Nurden AT. Congenital disorders associated with platelet dysfunctions. Thromb Haemost. 2008;99:253–63.PubMedGoogle Scholar
  30. 30.
    Hayward CP, Pai M, Liu Y, Moffat KA, Seecharan J, Webert KE, Cook RJ, Heddle NM. Diagnostic utility of light transmission platelet aggregometry: results from a prospective study of individuals referred for bleeding disorder assessments. J Thromb Haemost. 2009;7:676–84.PubMedCrossRefGoogle Scholar
  31. 31.
    Watson S, Daly M, Dawood B, Gissen P, Makris M, Mundell S, Wilde J, Mumford A. Phenotypic approaches to gene mapping in platelet function disorders – identification of new variant of P2Y12, TxA2 and GPVI receptors. Hamostaseologie. 2010;30:29–38.PubMedGoogle Scholar
  32. 32.
    Kouides PA, Kadir RA. Menorrhagia associated with laboratory abnormalities of hemostasis: epidemiological, diagnostic and therapeutic aspects. J Thromb Haemost. 2007;5 Suppl 1:175–82.PubMedCrossRefGoogle Scholar
  33. 33.
    Philipp CS, Dilley A, Miller CH, Evatt B, Baranwal A, Schwartz R, Bachmann G, Saidi P. Platelet functional defects in women with unexplained ­menorrhagia. J Thromb Haemost. 2003;1:477–84.PubMedCrossRefGoogle Scholar
  34. 34.
    Toogeh G, Sharifian R, Lak M, Safaee R, Artoni A, Peyvandi F. Presentation and pattern of symptoms in 382 patients with Glanzmann thrombasthenia in Iran. Am J Hematol. 2004;77:198–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Vivier M, Treisser A, Naett M, Diemunsch P, Schmitt JP, Waller C, Tongio MM, Hemmendinger S, Lutz P. Glanzmann’s thrombasthenia and pregnancy. Contribution of plasma exchange before scheduled cesarean section. J Gynecol Obstet Biol Reprod (Paris). 1989;18:507–13.Google Scholar
  36. 36.
    Bell JA, Savidge GF. Glanzmann’s thrombasthenia proposed optimal management during surgery and delivery. Clin Appl Thromb Hemost. 2003;9:167–70.PubMedCrossRefGoogle Scholar
  37. 37.
    Malhotra N, Chanana C, Deka D. Pregnancy in a patient of Glanzmann’s thrombasthenia. Indian J Med Sci. 2006;60:111–3.PubMedCrossRefGoogle Scholar
  38. 38.
    Caen JP, Castaldi PA, Leclerc JC, Inceman S, Larrieu MJ, Probst M, Bernard J. Congenital bleeding disorders with long bleeding time and normal platelet count I. Am J Med. 1966;41:4–26.CrossRefGoogle Scholar
  39. 39.
    Cézar Alencar de Lima R, Ana Lúcia de Castro F M, Regina Amélia Lopes P A, Vitor Hugo de M, Madalena Maria Ferreira M, Eduardo Barçante R, Lúcia Jamille A, Darci Ribeiro da S. Glanzmann’s thrombasthenia and pregnancy: a case report. J Bras Ginecol. 1998;108:375–8.Google Scholar
  40. 40.
    Heyes H, Scheck R, Rasche H. Obstetrical problems in patients with Glanzmann’s thrombasthenia. A casuistic presentation (author’s transl). Geburtshilfe Frauenheilkd. 1979;39:68–74.PubMedGoogle Scholar
  41. 41.
    Peitsidis P, Datta T, Pafilis I, Otomewo O, Tuddenham EG, Kadir RA. Bernard Soulier syndrome in pregnancy: a systematic review. Haemophilia. 2010;16:584–91.PubMedGoogle Scholar
  42. 42.
    Michalas S, Malamitsi-Puchner A, Tsevrenis H. Pregnancy and delivery in Bernard-Soulier syndrome. Acta Obstet Gynecol Scand. 1984;63:185–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Fujimori K, Ohto H, Honda S, Sato A. Antepartum diagnosis of fetal intracranial hemorrhage due to maternal Bernard-Soulier syndrome. Obstet Gynecol. 1999;94:817–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Zatik J, Poka R, Borsos A, Pfliegler G. Variable response of Hermansky-Pudlak syndrome to prophylactic administration of 1-desamino 8D-arginine in subsequent pregnancies. Eur J Obstet Gynecol Reprod Biol. 2002;104:165–6.PubMedCrossRefGoogle Scholar
  45. 45.
    Beesley RD, Robinson RD, Stewart TL. Two successful vaginal births after cesarean section in a patient with Hermansky-Pudlak syndrome who was treated with 1-deamino-8-arginine-vasopression during labor. Mil Med. 2008;173:1048–9.PubMedGoogle Scholar
  46. 46.
    Rahman SS, Myers JE, Gillham JC, Fitzmaurice R, Johnston TA. Post partum haemorrhage secondary to uterine atony, complicated by platelet storage pool disease and partial placenta diffusa: a case report. Cases J. 2008;1:393.PubMedCrossRefGoogle Scholar
  47. 47.
    Chi C, Lee CA, England A, Hingorani J, Paintsil J, Kadir RA. Obstetric analgesia and anaesthesia in women with inherited bleeding disorders. Thromb Haemost. 2009;101:1104–11.PubMedGoogle Scholar
  48. 48.
    Awidi AS. Delivery of infants with Glanzmann thrombasthenia and subsequent blood transfusion requirements: a follow-up of 39 patients. Am J Hematol. 1992;40:1–4.PubMedCrossRefGoogle Scholar
  49. 49.
    Leticee N, Kaplan C, Lemery D. Pregnancy in mother with Glanzmann’s thrombasthenia and isoantibody against GPIIb-IIIa: is there a foetal risk? Eur J Obstet Gynecol Reprod Biol. 2005;121:139–42.PubMedCrossRefGoogle Scholar
  50. 50.
    Kashyap R, Kriplani A, Saxena R, Takkar D, Choudhry VP. Pregnancy in a patient of Glanzmann’s thrombasthenia with antiplatelet antibodies. J Obstet Gynaecol Res. 1997;23:247–50.PubMedGoogle Scholar
  51. 51.
    Uotila J, Tammela O, Makipernaa A. Fetomaternal platelet immunization associated with maternal Bernard-Soulier syndrome. Am J Perinatol. 2008;25:219–23.PubMedCrossRefGoogle Scholar
  52. 52.
    Peng TC, Kickler TS, Bell WR, Haller E. Obstetric complications in a patient with Bernard-Soulier syndrome. Am J Obstet Gynecol. 1991;165:425–6.PubMedGoogle Scholar
  53. 53.
    Monrigal C, Beurrier P, Mercier FJ, Boyer-Neumann C, Gillard P. Glanzmann’s thrombasthenia and pregnancy: a case and review of the literature. Ann Fr Anesth Reanim. 2003;22:826–30.PubMedCrossRefGoogle Scholar
  54. 54.
    Alamelu J, Liesner R. Modern management of severe platelet function disorders. Br J Haematol. 2010;149:813–23.PubMedCrossRefGoogle Scholar
  55. 55.
    Bellucci S, Caen J. Molecular basis of Glanzmann’s Thrombasthenia and current strategies in treatment. Blood Rev. 2002;16:193–202.PubMedCrossRefGoogle Scholar
  56. 56.
    Kaufmann JE, Vischer UM. Cellular mechanisms of the hemostatic effects of desmopressin (DDAVP). J Thromb Haemost. 2003;1:682–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Mannucci PM. Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood. w1997;90:2515–21.PubMedGoogle Scholar
  58. 58.
    Cohen AJ, Kessler CM, Ewenstein BM. Management of von Willebrand disease: a survey on current clinical practice from the haemophilia centres of North America. Haemophilia. 2001;7:235–41.PubMedCrossRefGoogle Scholar
  59. 59.
    Ray JG. DDAVP use during pregnancy: an analysis of its safety for mother and child. Obstet Gynecol Surv. 1998;53:450–5.PubMedCrossRefGoogle Scholar
  60. 60.
    Mannucci PM. Use of desmopressin (DDAVP) during early pregnancy in factor VIII-deficient women. Blood. 2005;105:3382.PubMedCrossRefGoogle Scholar
  61. 61.
    Nolan B, White B, Smith J, O’Reily C, Fitzpatrick B, Smith OP. Desmopressin: therapeutic limitations in children and adults with inherited coagulation ­disorders. Br J Haematol. 2000;109:865–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Hers I, Mumford A. Understanding the therapeutic action of recombinant factor VIIa in platelet disorders. Platelets. 2008;19:571–81.PubMedCrossRefGoogle Scholar
  63. 63.
    Poon MC, D’Oiron R, Von Depka M, Khair K, Negrier C, Karafoulidou A, Huth-Kuehne A, Morfini M. Prophylactic and therapeutic recombinant factor VIIa administration to patients with Glanzmann’s thrombasthenia: results of an international survey. J Thromb Haemost. 2004;2:1096–103.PubMedCrossRefGoogle Scholar
  64. 64.
    Almeida AM, Khair K, Hann I, Liesner R. The use of recombinant factor VIIa in children with inherited platelet function disorders. Br J Haematol. 2003;121:477–81.PubMedCrossRefGoogle Scholar
  65. 65.
    Poon MC. The evidence for the use of recombinant human activated factor VII in the treatment of bleeding patients with quantitative and qualitative platelet disorders. Transfus Med Rev. 2007;21:223–36.PubMedCrossRefGoogle Scholar
  66. 66.
    Alfirevic Z, Elbourne D, Pavord S, Bolte A, Van Geijn H, Mercier F, Ahonen J, Bremme K, Bodker B, Magnusdottir EM, Salvesen K, Prendiville W, Truesdale A, Clemens F, Piercy D, Gyte G. Use of recombinant activated factor VII in primary postpartum hemorrhage: the Northern European registry 2000-2004. Obstet Gynecol. 2007;110:1270–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Franchini M, Franchi M, Bergamini V, Montagnana M, Salvagno GL, Targher G, Lippi G. The use of recombinant activated FVII in postpartum hemorrhage. Clin Obstet Gynecol. 2010;53:219–27.PubMedCrossRefGoogle Scholar
  68. 68.
    British Committee for Standards in Haematology, Blood Transfusion Task Force. Guidelines for the use of platelet transfusions. Br J Haematol. 2003;122:10–23.CrossRefGoogle Scholar
  69. 69.
    Ponte ML. Insights into the management of emerging infections: regulating variant Creutzfeldt-Jakob ­disease transfusion risk in the UK and the US. PLoS Med. 2006;3:e342.PubMedCrossRefGoogle Scholar
  70. 70.
    Novotny VM. Prevention and management of platelet transfusion refractoriness. Vox Sang. 1999;76:1–13.PubMedCrossRefGoogle Scholar
  71. 71.
    Dede M, Ural AU, Yenen M, Mesten Z, Baser I. Glanzmann’s thrombasthenia in two pregnant females. Am J Hematol. 2007;82:330–1.PubMedCrossRefGoogle Scholar
  72. 72.
    Kale A, Bayhan G, Yalinkaya A, Yayla M. The use of recombinant factor VIla in a primigravida with Glanzmann’s thrombasthenia during delivery. J Perinat Med. 2004;32:456–8.PubMedCrossRefGoogle Scholar
  73. 73.
    Monte S, Lyons G. Peripartum management of a patient with Glanzmann’s thrombasthenia using Thrombelastograph. Br J Anaesth. 2002;88:734–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Sugihara S, Katsutani S, Hyodo H, Hyodo M, Kudo Y, Fujii T, Kimura A. Postpartum hemorrhage successfully treated with recombinant factor VIIa in Glanzmann thromboasthenia. Rinsho Ketsueki. 2008;49:46–50.PubMedGoogle Scholar
  75. 75.
    Peaceman AM, Katz AR, Laville M. Bernard-Soulier syndrome complicating pregnancy: a case report. Obstet Gynecol. 1989;73:457–9.PubMedGoogle Scholar
  76. 76.
    Ito K, Yoshida H, Hatoyama H, Matsumoto H, Ban C, Mori T, Sugiyama T, Ishibashi T, Okuma M, Uchino H, et al. Antibody removal therapy used successfully at delivery of a pregnant patient with Glanzmann’s thrombasthenia and multiple anti-platelet antibodies. Vox Sang. 1991;61:40–6.PubMedCrossRefGoogle Scholar
  77. 77.
    Birchall JE, Murphy MF, Kaplan C, Kroll H. European collaborative study of the antenatal management of feto-maternal alloimmune thrombocytopenia. Br J Haematol. 2003;122:275–88.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2012

Authors and Affiliations

  1. 1.Bristol Heart Institute, University of BristolBristolUK
  2. 2.Bristol Haemophilia CentreUniversity Hospitals NHS Foundation TrustBristolUK

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