Download PDF
Semin Thromb Hemost 2011; 37(6): 640-652
DOI: 10.1055/s-0031-1291374
© Thieme Medical Publishers

Thrombocytopenia and Disorders of Platelet Function in Pregnancy

Rezan A. Kadir1 , Claire McLintock2
  • 1Haemophilia Centre & Thrombosis Unit, Department of Obstetrics and Gynecology, The Royal Free Hospital, London, United Kingdom
  • 2National Women's Health, Auckland City Hospital, Auckland, New Zealand
Further Information

Publication History

Publication Date:
18 November 2011 (online)

    Permissions and Reprints

ABSTRACT

Pregnancy is associated with physiological and pathological changes in platelet numbers and function, which can be of clinical concern because of risks for maternal and fetal or neonatal bleeding. Thrombocytopenia in pregnancy is frequently encountered and may be due to increased platelet turnover and plasma dilution, immune-mediated mechanisms, or a complication of a more severe underlying pregnancy-related disorder such as preeclampsia. Inherited defects in platelet function and number may also manifest during pregnancy with the risk of bleeding dependent on the underlying problem. In some women, the diagnosis of thrombocytopenia will precede pregnancy but in others, the problem is first identified when routine pregnancy blood tests are performed. An accurate diagnosis and risk assessment in the antenatal period are essential for developing specific plans for any antenatal interventions and for management of delivery and the postpartum periods, and the neonate. Management of pregnant women with platelet disorders requires a multidisciplinary approach and close collaboration between the obstetric and hematology teams.

KEYWORDS

Immune thrombocytopenia - gestational thrombocytopenia - thrombocytopenia with pregnancy - neonatal alloimmune thrombocytopenia

REFERENCES

  • 1 Burrows R F, Kelton J G. Thrombocytopenia at delivery: a prospective survey of 6715 deliveries.  Am J Obstet Gynecol. 1990;  162 (3) 731-734
    Google Scholar
  • 2 Sheu J R, Hsiao G, Lin W Y et al.. Mechanisms involved in agonist-induced hyperaggregability of platelets from normal pregnancy.  J Biomed Sci. 2002;  9 (1) 17-25
    Google Scholar
  • 3 Janes S L, Kyle P M, Redman C, Goodall A H. Flow cytometric detection of activated platelets in pregnant women prior to the development of pre-eclampsia.  Thromb Haemost. 1995;  74 (4) 1059-1063
    Google Scholar
  • 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 (1) 117-118
    Google Scholar
  • 5 Gatti L, Tenconi P M, Guarneri D et al.. Hemostatic parameters and platelet activation by flow-cytometry in normal pregnancy: a longitudinal study.  Int J Clin Lab Res. 1994;  24 (4) 217-219
    Google Scholar
  • 6 Harlow F H, Brown M A, Brighton T A et al.. Platelet activation in the hypertensive disorders of pregnancy.  Am J Obstet Gynecol. 2002;  187 (3) 688-695
    Google Scholar
  • 7 Sheu J R, Hsiao G, Shen M Y, Lin W Y, Tzeng C R. The hyperaggregability of platelets from normal pregnancy is mediated through thromboxane A2 and cyclic AMP pathways.  Clin Lab Haematol. 2002;  24 (2) 121-129
    Google Scholar
  • 8 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 (4) 896-900
    Google Scholar
  • 9 Nicolini U, Guarneri D, Gianotti G A, Campagnoli C, Crosignani P G, Gatti L. Maternal and fetal platelet activation in normal pregnancy.  Obstet Gynecol. 1994;  83 (1) 65-69
    Google Scholar
  • 10 Kazmi R S, Cooper A J, Lwaleed B A. Platelet function in pre-eclampsia.  Semin Thromb Hemost. 2011;  37 (2) 131-136
    Google Scholar
  • 11 Burrows R F, Kelton J G. Fetal thrombocytopenia and its relation to maternal thrombocytopenia.  N Engl J Med. 1993;  329 (20) 1463-1466
    Google Scholar
  • 12 Sainio S, Kekomäki R, Riikonen S, Teramo K. Maternal thrombocytopenia at term: a population-based study.  Acta Obstet Gynecol Scand. 2000;  79 (9) 744-749
    Google Scholar
  • 13 Boehlen F, Hohlfeld P, Extermann P, Perneger T V, de Moerloose P. Platelet count at term pregnancy: a reappraisal of the threshold.  Obstet Gynecol. 2000;  95 (1) 29-33
    Google Scholar
  • 14 Schwartz R S. Immune thrombocytopenic purpura—from agony to agonist.  N Engl J Med. 2007;  357 (22) 2299-2301
    Google Scholar
  • 15 Segal J B, Powe N R. Prevalence of immune thrombocytopenia: analyses of administrative data.  J Thromb Haemost. 2006;  4 (11) 2377-2383
    Google Scholar
  • 16 Provan D, Stasi R, Newland A C et al.. International consensus report on the investigation and management of primary immune thrombocytopenia.  Blood. 2010;  115 (2) 168-186
    Google Scholar
  • 17 Chang M, Nakagawa P A, Williams S A et al.. Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro.  Blood. 2003;  102 (3) 887-895
    Google Scholar
  • 18 Garty B Z, Ludomirsky A, Danon Y L, Peter J B, Douglas S D. Placental transfer of immunoglobulin G subclasses.  Clin Diagn Lab Immunol. 1994;  1 (6) 667-669
    Google Scholar
  • 19 Webert K E, Mittal R, Sigouin C, Heddle N M, Kelton J G. A retrospective 11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura.  Blood. 2003;  102 (13) 4306-4311
    Google Scholar
  • 20 Fujimura K, Harada Y, Fujimoto T et al.. Nationwide study of idiopathic thrombocytopenic purpura in pregnant women and the clinical influence on neonates.  Int J Hematol. 2002;  75 (4) 426-433
    Google Scholar
  • 21 Yamada H, Fujimoto S. Perinatal management of idiopathic thrombocytopenic purpura in pregnancy: risk factors for passive immune thrombocytopenia.  Ann Hematol. 1994;  68 (1) 39-42
    Google Scholar
  • 22 Sharon R, Tatarsky I. Low fetal morbidity in pregnancy associated with acute and chronic idiopathic thrombocytopenic purpura.  Am J Hematol. 1994;  46 (2) 87-90
    Google Scholar
  • 23 Samuels P, Bussel J B, Braitman L E et al.. Estimation of the risk of thrombocytopenia in the offspring of pregnant women with presumed immune thrombocytopenic purpura.  N Engl J Med. 1990;  323 (4) 229-235
    Google Scholar
  • 24 Cook R L, Miller R C, Katz V L, Cefalo R C. Immune thrombocytopenic purpura in pregnancy: a reappraisal of management.  Obstet Gynecol. 1991;  78 (4) 578-583
    Google Scholar
  • 25 al-Mofada S M, Osman M E, Kides E, al-Momen A K, al Herbish A S, al-Mobaireek K. Risk of thrombocytopenia in the infants of mothers with idiopathic thrombocytopenia.  Am J Perinatol. 1994;  11 (6) 423-426
    Google Scholar
  • 26 Moutet A, Fromont P, Farcet J P et al.. Pregnancy in women with immune thrombocytopenic purpura.  Arch Intern Med. 1990;  150 (10) 2141-2145
    Google Scholar
  • 27 Valat A S, Caulier M T, Devos P et al.. Relationships between severe neonatal thrombocytopenia and maternal characteristics in pregnancies associated with autoimmune thrombocytopenia.  Br J Haematol. 1998;  103 (2) 397-401
    Google Scholar
  • 28 Kelton J G, Inwood M J, Barr R M et al.. The prenatal prediction of thrombocytopenia in infants of mothers with clinically diagnosed immune thrombocytopenia.  Am J Obstet Gynecol. 1982;  144 (4) 449-454
    Google Scholar
  • 29 Burrows R F, Kelton J G. Low fetal risks in pregnancies associated with idiopathic thrombocytopenic purpura.  Am J Obstet Gynecol. 1990;  163 (4 Pt 1) 1147-1150
    Google Scholar
  • 30 Kaplan C, Daffos F, Forestier F et al.. Fetal platelet counts in thrombocytopenic pregnancy.  Lancet. 1990;  336 (8721) 979-982
    Google Scholar
  • 31 Payne S D, Resnik R, Moore T R, Hedriana H L, Kelly T F. Maternal characteristics and risk of severe neonatal thrombocytopenia and intracranial hemorrhage in pregnancies complicated by autoimmune thrombocytopenia.  Am J Obstet Gynecol. 1997;  177 (1) 149-155
    Google Scholar
  • 32 Scott J R, Cruikshank D P, Kochenour N K, Pitkin R M, Warenski J C. Fetal platelet counts in the obstetric management of immunologic thrombocytopenic purpura.  Am J Obstet Gynecol. 1980;  136 (4) 495-499
    Google Scholar
  • 33 McLintock C, Repke J T, Bucklin B. Hematologic disease in pregnancy. In: Powrie R, Greene M, Camann W, eds. de Swiet's Medical Disorders in Obstetric Practice. 5th ed. Oxford: Wiley-Blackwell; 2011: 48-81
    Google Scholar
  • 34 Christiaens G C, Nieuwenhuis H K, Bussel J B. Comparison of platelet counts in first and second newborns of mothers with immune thrombocytopenic purpura.  Obstet Gynecol. 1997;  90 (4 Pt 1) 546-552
    Google Scholar
  • 35 Michel M, Novoa M V, Bussel J B. Intravenous anti-D as a treatment for immune thrombocytopenic purpura (ITP) during pregnancy.  Br J Haematol. 2003;  123 (1) 142-146
    Google Scholar
  • 36 Arnold D M, Dentali F, Crowther M A et al.. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura.  Ann Intern Med. 2007;  146 (1) 25-33
    Google Scholar
  • 37 Klink D T, van Elburg R M, Schreurs M W, van Well G T. Rituximab administration in third trimester of pregnancy suppresses neonatal B-cell development.  Clin Dev Immunol. 2008;  2008 271-363
    Google Scholar
  • 38 Corman S L, Mohammad R A. Eltrombopag: a novel oral thrombopoietin receptor agonist.  Ann Pharmacother. 2010;  44 (6) 1072-1079
    Google Scholar
  • 39 Hubulashvili D, Marzella N. Romiplostim (Nplate), a treatment option for immune (idiopathic) thrombocytopenic purpura.  P T. 2009;  34 (9) 482-485
    Google Scholar
  • 40 Moen V. Scandinavian guidelines for neuraxial block and disturbed haemostasis: replacing wishful thinking with evidence based caution.  Acta Anaesthesiol Scand. 2010;  54 (1) 6-8
    Google Scholar
  • 41 van Veen J J, Nokes T J, Makris M. The risk of spinal haematoma following neuraxial anaesthesia or lumbar puncture in thrombocytopenic individuals.  Br J Haematol. 2010;  148 (1) 15-25
    Google Scholar
  • 42 Althaus K, Greinacher A. MYH9-related platelet disorders.  Semin Thromb Hemost. 2009;  35 (2) 189-203
    Google Scholar
  • 43 Fishman E B, Connors J M, Camann W R. Anesthetic management of seven deliveries in three sisters with the May-Hegglin anomaly.  Anesth Analg. 2009;  108 (5) 1603-1605
    Google Scholar
  • 44 Urato A C, Repke J T. May-Hegglin anomaly: a case of vaginal delivery when both mother and fetus are affected.  Am J Obstet Gynecol. 1998;  179 (1) 260-261
    Google Scholar
  • 45 Rick M E, Williams S B, Sacher R A, McKeown L P. Thrombocytopenia associated with pregnancy in a patient with type IIB von Willebrand's disease.  Blood. 1987;  69 (3) 786-789
    Google Scholar
  • 46 Kujovich J L. von Willebrand disease and pregnancy.  J Thromb Haemost. 2005;  3 (2) 246-253
    Google Scholar
  • 47 Lee C A, Chi C, Pavord S R UK Haemophilia Centre Doctors' Organization et al. The obstetric and gynaecological management of women with inherited bleeding disorders—review with guidelines produced by a taskforce of UK Haemophilia Centre Doctors' Organization.  Haemophilia. 2006;  12 (4) 301-336
    Google Scholar
  • 48 Israels S J, El-Ekiaby M, Quiroga T, Mezzano D. Inherited disorders of platelet function and challenges to diagnosis of mucocutaneous bleeding.  Haemophilia. 2010;  16 (Suppl 5) 152-159
    Google Scholar
  • 49 Hayward C P. Diagnosis and management of mild bleeding disorders.  Hematology Am Soc Hematol Educ Program. 2005;  423-428
    Google Scholar
  • 50 Greaves M, Watson H G. Approach to the diagnosis and management of mild bleeding disorders.  J Thromb Haemost. 2007;  5 (Suppl 1) 167-174
    Google Scholar
  • 51 Hayward C P, Eikelboom J. Platelet function testing: quality assurance.  Semin Thromb Hemost. 2007;  33 (3) 273-282
    Google Scholar
  • 52 Philipp C S, Dilley A, Miller C H et al.. Platelet functional defects in women with unexplained menorrhagia.  J Thromb Haemost. 2003;  1 (3) 477-484
    Google Scholar
  • 53 Bevan J A, Maloney K W, Hillery C A, Gill J C, Montgomery R R, Scott J P. Bleeding disorders: A common cause of menorrhagia in adolescents.  J Pediatr. 2001;  138 (6) 856-861
    Google Scholar
  • 54 Miller C H, Philipp C S, Stein S F et al.. The spectrum of haemostatic characteristics of women with unexplained menorrhagia.  Haemophilia. 2011;  17 (1) e223-e229
    Google Scholar
  • 55 Nurden A T, Caen J P. Specific roles for platelet surface glycoproteins in platelet function.  Nature. 1975;  255 (5511) 720-722
    Google Scholar
  • 56 Nurden A T, Nurden P. Inherited defects of platelet function.  Rev Clin Exp Hematol. 2001;  5 (4) 314-334 quiz 431
    Google Scholar
  • 57 López J A, Andrews R K, Afshar-Kharghan V, Berndt M C. Bernard-Soulier syndrome.  Blood. 1998;  91 (12) 4397-4418
    Google Scholar
  • 58 Peitsidis P, Datta T, Pafilis I, Otomewo O, Tuddenham E G, Kadir R A. Bernard Soulier syndrome in pregnancy: a systematic review.  Haemophilia. 2010;  16 (4) 584-591
    Google Scholar
  • 59 Fujimori K, Ohto H, Honda S, Sato A. Antepartum diagnosis of fetal intracranial hemorrhage due to maternal Bernard-Soulier syndrome.  Obstet Gynecol. 1999;  94 (5 Pt 2) 817-819
    Google Scholar
  • 60 Peng T C, Kickler T S, Bell W R, Haller E. Obstetric complications in a patient with Bernard-Soulier syndrome.  Am J Obstet Gynecol. 1991;  165 (2) 425-426
    Google Scholar
  • 61 George J N, Caen J P, Nurden A T. Glanzmann's thrombasthenia: the spectrum of clinical disease.  Blood. 1990;  75 (7) 1383-1395
    Google Scholar
  • 62 Santoro C, Rago A, Biondo F et al.. Prevalence of allo-immunization anti-HLA and anti-integrin alphaIIbbeta3 in Glanzmann Thromboasthenia patients.  Haemophilia. 2010;  16 (5) 805-812
    Google Scholar
  • 63 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 (2) 198-199
    Google Scholar
  • 64 Heyes H, Scheck R, Rasche H. [Obstetrical problems in patients with Glanzmann's thrombasthenia. A casuistic presentation (author's transl)].  Geburtshilfe Frauenheilkd. 1979;  39 (1) 68-74
    Google Scholar
  • 65 Bayraktaroglu T, Colak N, Nalcaci M, Yenerel M N. Sheehan's syndrome associated with Glanzmann's Thrombasthenia: case report and literature review.  Exp Clin Endocrinol Diabetes. 2008;  116 (9) 549-553
    Google Scholar
  • 66 Leibowitz G, Salameh M, Gomori M J, Reubinoff C A, Rösler A, Gross D J. Thrombasthenia—a rare cause of Sheehan's syndrome.  Acta Obstet Gynecol Scand. 1995;  74 (6) 482-484
    Google Scholar
  • 67 Léticée N, Kaplan C, Lémery 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 (2) 139-142
    Google Scholar
  • 68 Boval B, Bellucci S, Boyer-Neumann C. Glanzmann's thrombasthenia and pregnancy: clinical observations and management of four affected women.  Thromb Haemost. 2001(Suppl);  1154
    Google Scholar
  • 69 Pico M RA, Martin C, Zuazu J, Monasterio J. Glanzmann thromboasthenia in pregnancy: clincial features and platelet serology.  Thromb Haemost. 1987;  58 475
    Google Scholar
  • 70 Hayward C P, Rao A K, Cattaneo M. Congenital platelet disorders: overview of their mechanisms, diagnostic evaluation and treatment.  Haemophilia. 2006;  12 (Suppl 3) 128-136
    Google Scholar
  • 71 Birchall J E, Murphy M F, Kaplan C, Kroll H. European Fetomaternal Alloimmune Thrombocytopenia Study Group . European collaborative study of the antenatal management of feto-maternal alloimmune thrombocytopenia.  Br J Haematol. 2003;  122 (2) 275-288
    Google Scholar
  • 72 Bolton-Maggs P H, Chalmers E A, Collins P W UKHCDO et al. A review of inherited platelet disorders with guidelines for their management on behalf of the UKHCDO.  Br J Haematol. 2006;  135 (5) 603-633
    Google Scholar
  • 73 Overton T G, Duncan K R, Jolly M, Letsky E, Fisk N M. Serial aggressive platelet transfusion for fetal alloimmune thrombocytopenia: platelet dynamics and perinatal outcome.  Am J Obstet Gynecol. 2002;  186 (4) 826-831
    Google Scholar
  • 74 van den Akker E S, Oepkes D, Lopriore E, Brand A, Kanhai H H. Noninvasive antenatal management of fetal and neonatal alloimmune thrombocytopenia: safe and effective.  BJOG. 2007;  114 (4) 469-473
    Google Scholar
  • 75 Giers G, Wenzel F, Stockschläder M, Riethmacher R, Lorenz H, Tutschek B. Fetal alloimmune thrombocytopenia and maternal intravenous immunoglobulin infusion.  Haematologica. 2010;  95 (11) 1921-1926
    Google Scholar
  • 76 Lowenwirt I, Dadic P, Krishnamurthy V. Essential thrombocythemia and epidural analgesia in the parturient. Does thromboelastography help?.  Reg Anesth. 1996;  21 (6) 525-528
    Google Scholar
  • 77 Othman M, Falcón B J, Kadir R. Global hemostasis in pregnancy: are we using thromboelastography to its full potential?.  Semin Thromb Hemost. 2010;  36 (7) 738-746
    Google Scholar
  • 78 Alamelu J, Liesner R. Modern management of severe platelet function disorders.  Br J Haematol. 2010;  149 (6) 813-823
    Google Scholar
  • 79 Riddel A, Kadir R, Pollard D, Tuddenham E G, Gomez K. Monitoring low dose recombinant factor VIIa therapy in patients with severe factor XI deficiency undergoing surgery.  Thromb Haemost. 2011;  106 (3) 521-527
    Google Scholar
  • 80 Viuff D, Andersen S, Sørensen B B, Lethagen S. Optimizing thrombelastography (TEG) assay conditions to monitor rFVIIa (NovoSeven) therapy in haemophilia A patients.  Thromb Res. 2010;  126 (2) 144-149
    Google Scholar
  • 81 Chi C, Lee C A, England A, Hingorani J, Paintsil J, Kadir R A. Obstetric analgesia and anaesthesia in women with inherited bleeding disorders.  Thromb Haemost. 2009;  101 (6) 1104-1111
    Google Scholar
  • 82 Poddar R K, Coley S, Pavord S. Hermansky-Pudlak syndrome in a pregnant patient.  Br J Anaesth. 2004;  93 (5) 740-742
    Google Scholar

Rezan A KadirM.B. Ch.B. M.D. M.R.C.O.G. F.R.C.S. (Ed) 

Haemophilia Centre & Thrombosis Unit, Department of Obstetrics and Gynecology

The Royal Free Hospital, London NW3 2QG, UK

Email: rezan.abdul-kadir@nhs.uk

      >