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Neonatal alloimmune thrombocytopenia: Parental evaluation and pregnancy management

Author
Michael J Paidas, MD
Section Editor
Louise Wilkins-Haug, MD, PhD
Deputy Editor
Vanessa A Barss, MD, FACOG

INTRODUCTION

Neonatal alloimmune thrombocytopenia (NAIT) is a disorder in which fetal platelets contain an antigen inherited from the father that the mother lacks, most commonly human platelet antigen (HPA)-1a incompatibility. The mother then develops antibodies against this paternal antigen and these antibodies cross the placenta and bind to the fetal platelets. Clearance of the antibody-coated platelets results in fetal/neonatal thrombocytopenia. In contrast to Rh(D) alloimmunization, NAIT often affects a first pregnancy and maternal anti-platelet antibody titers are not predictive of the degree of fetal thrombocytopenia [1].

This topic will provide a brief overview of NAIT and discuss parental evaluation and management of affected pregnancies. Postnatal issues are reviewed separately. (See "Causes of neonatal thrombocytopenia", section on 'Fetal and neonatal alloimmune thrombocytopenia'.)

BACKGROUND

All of the following criteria are necessary to diagnosis neonatal alloimmune thrombocytopenia:

Fetal or neonatal thrombocytopenia

Identification of a paternal, fetal, or neonatal platelet antigen that the mother lacks

                 

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Literature review current through: May 2015. | This topic last updated: Jun 17, 2015.
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References
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  1. Bussel JB, Berkowitz RL, Lynch L, et al. Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin. Am J Obstet Gynecol 1996; 174:1414.
  2. Bussel JB, Zabusky MR, Berkowitz RL, McFarland JG. Fetal alloimmune thrombocytopenia. N Engl J Med 1997; 337:22.
  3. Mueller-Eckhardt C, Kiefel V, Grubert A, et al. 348 cases of suspected neonatal alloimmune thrombocytopenia. Lancet 1989; 1:363.
  4. Herman JH, Jumbelic MI, Ancona RJ, Kickler TS. In utero cerebral hemorrhage in alloimmune thrombocytopenia. Am J Pediatr Hematol Oncol 1986; 8:312.
  5. Paidas MJ, Berkowitz RL, Lynch L, et al. Alloimmune thrombocytopenia: fetal and neonatal losses related to cordocentesis. Am J Obstet Gynecol 1995; 172:475.
  6. Kjeldsen-Kragh J, Killie MK, Tomter G, et al. A screening and intervention program aimed to reduce mortality and serious morbidity associated with severe neonatal alloimmune thrombocytopenia. Blood 2007; 110:833.
  7. Williamson LM, Hackett G, Rennie J, et al. The natural history of fetomaternal alloimmunization to the platelet-specific antigen HPA-1a (PlA1, Zwa) as determined by antenatal screening. Blood 1998; 92:2280.
  8. Davoren A, Curtis BR, Aster RH, McFarland JG. Human platelet antigen-specific alloantibodies implicated in 1162 cases of neonatal alloimmune thrombocytopenia. Transfusion 2004; 44:1220.
  9. Yinon Y, Spira M, Solomon O, et al. Antenatal noninvasive treatment of patients at risk for alloimmune thrombocytopenia without a history of intracranial hemorrhage. Am J Obstet Gynecol 2006; 195:1153.
  10. Birchall JE, Murphy MF, Kaplan C, et al. European collaborative study of the antenatal management of feto-maternal alloimmune thrombocytopenia. Br J Haematol 2003; 122:275.
  11. Murphy MF, Hambley H, Nicolaides K, Waters AH. Severe fetomaternal alloimmune thrombocytopenia presenting with fetal hydrocephalus. Prenat Diagn 1996; 16:1152.
  12. Li C, Piran S, Chen P, et al. The maternal immune response to fetal platelet GPIbα causes frequent miscarriage in mice that can be prevented by intravenous IgG and anti-FcRn therapies. J Clin Invest 2011; 121:4537.
  13. Ni H, Chen P, Spring CM, et al. A novel murine model of fetal and neonatal alloimmune thrombocytopenia: response to intravenous IgG therapy. Blood 2006; 107:2976.
  14. Pacheco LD, Berkowitz RL, Moise KJ Jr, et al. Fetal and neonatal alloimmune thrombocytopenia: a management algorithm based on risk stratification. Obstet Gynecol 2011; 118:1157.
  15. Peterson JA, McFarland JG, Curtis BR, Aster RH. Neonatal alloimmune thrombocytopenia: pathogenesis, diagnosis and management. Br J Haematol 2013; 161:3.
  16. Berkowitz RL, Bussel JB, McFarland JG. Alloimmune thrombocytopenia: state of the art 2006. Am J Obstet Gynecol 2006; 195:907.
  17. Peterson JA, Kanack A, Nayak D, et al. Prevalence and clinical significance of low-avidity HPA-1a antibodies in women exposed to HPA-1a during pregnancy. Transfusion 2013; 53:1309.
  18. Gramatges MM, Fani P, Nadeau K, et al. Neonatal alloimmune thrombocytopenia and neutropenia associated with maternal human leukocyte antigen antibodies. Pediatr Blood Cancer 2009; 53:97.
  19. del Rosario ML, Fox ER, Kickler TS, Kao KJ. Neonatal alloimmune thrombocytopenia associated with maternal anti-HLA antibody: a case report. J Pediatr Hematol Oncol 1998; 20:252.
  20. Sasaki M, Yagihashi A, Kobayashi D, et al. Neonatal alloimmune thrombocytopenia due to anti-human leukocyte antigen antibody: a case report. Pediatr Hematol Oncol 2001; 18:519.
  21. Lipitz S, Ryan G, Murphy MF, et al. Neonatal alloimmune thrombocytopenia due to anti-P1A1 (anti-HPA-1a): importance of paternal and fetal platelet typing for assessment of fetal risk. Prenat Diagn 1992; 12:955.
  22. Tiller H, Killie MK, Skogen B, et al. Neonatal alloimmune thrombocytopenia in Norway: poor detection rate with nonscreening versus a general screening programme. BJOG 2009; 116:594.
  23. Turner ML, Bessos H, Fagge T, et al. Prospective epidemiologic study of the outcome and cost-effectiveness of antenatal screening to detect neonatal alloimmune thrombocytopenia due to anti-HPA-1a. Transfusion 2005; 45:1945.
  24. Durand-Zaleski I, Schlegel N, Blum-Boisgard C, et al. Screening primiparous women and newborns for fetal/neonatal alloimmune thrombocytopenia: a prospective comparison of effectiveness and costs. Immune Thrombocytopenia Working Group. Am J Perinatol 1996; 13:423.
  25. Killie MK, Kjeldsen-Kragh J, Husebekk A, et al. Cost-effectiveness of antenatal screening for neonatal alloimmune thrombocytopenia. BJOG 2007; 114:588.
  26. Kamphuis MM, Paridaans N, Porcelijn L, et al. Screening in pregnancy for fetal or neonatal alloimmune thrombocytopenia: systematic review. BJOG 2010; 117:1335.
  27. Rayment R, Brunskill SJ, Stanworth S, et al. Antenatal interventions for fetomaternal alloimmune thrombocytopenia. Cochrane Database Syst Rev 2005; :CD004226.
  28. Vinograd CA, Bussel JB. Antenatal treatment of fetal alloimmune thrombocytopenia: a current perspective. Haematologica 2010; 95:1807.
  29. Ohto H, Kato K, Tohyama Y, et al. Prenatal determination of human platelet antigen type 4 by DNA amplification of amniotic fluid cells. Transfus Sci 1997; 18:85.
  30. Quintanar A, Jallu V, Legros Y, Kaplan C. Human platelet antigen genotyping using a fluorescent SSCP technique with an automatic sequencer. Br J Haematol 1998; 103:437.
  31. Scheffer PG, Ait Soussan A, Verhagen OJ, et al. Noninvasive fetal genotyping of human platelet antigen-1a. BJOG 2011; 118:1392.
  32. van den Akker ES, Oepkes D, Lopriore E, et al. Noninvasive antenatal management of fetal and neonatal alloimmune thrombocytopenia: safe and effective. BJOG 2007; 114:469.
  33. Berkowitz RL, Lesser ML, McFarland JG, et al. Antepartum treatment without early cordocentesis for standard-risk alloimmune thrombocytopenia: a randomized controlled trial. Obstet Gynecol 2007; 110:249.
  34. van den Akker E, Oepkes D, Brand A, Kanhai HH. Vaginal delivery for fetuses at risk of alloimmune thrombocytopenia? BJOG 2006; 113:781.
  35. Althaus J, Weir EG, Askin F, et al. Chronic villitis in untreated neonatal alloimmune thrombocytopenia: an etiology for severe early intrauterine growth restriction and the effect of intravenous immunoglobulin therapy. Am J Obstet Gynecol 2005; 193:1100.
  36. Kay HH, Hage ML, Kurtzberg J, Dunsmore KP. Alloimmune thrombocytopenia may be associated with systemic disease. Am J Obstet Gynecol 1992; 166:110.
  37. Bussel JB, Berkowitz RL, Hung C, et al. Intracranial hemorrhage in alloimmune thrombocytopenia: stratified management to prevent recurrence in the subsequent affected fetus. Am J Obstet Gynecol 2010; 203:135.e1.
  38. Berkowitz RL, Kolb EA, McFarland JG, et al. Parallel randomized trials of risk-based therapy for fetal alloimmune thrombocytopenia. Obstet Gynecol 2006; 107:91.
  39. Kamphuis MM, Oepkes D. Fetal and neonatal alloimmune thrombocytopenia: prenatal interventions. Prenat Diagn 2011; 31:712.
  40. Thung SF, Grobman WA. The cost effectiveness of empiric intravenous immunoglobulin for the antepartum treatment of fetal and neonatal alloimmune thrombocytopenia. Am J Obstet Gynecol 2005; 193:1094.
  41. Murphy MF, Waters AH, Doughty HA, et al. Antenatal management of fetomaternal alloimmune thrombocytopenia--report of 15 affected pregnancies. Transfus Med 1994; 4:281.
  42. Overton TG, Duncan KR, Jolly M, et al. Serial aggressive platelet transfusion for fetal alloimmune thrombocytopenia: platelet dynamics and perinatal outcome. Am J Obstet Gynecol 2002; 186:826.
  43. Berger M. Adverse effects of IgG therapy. J Allergy Clin Immunol Pract 2013; 1:558.
  44. Radder CM, de Haan MJ, Brand A, et al. Follow up of children after antenatal treatment for alloimmune thrombocytopenia. Early Hum Dev 2004; 80:65.
  45. Ward MJ, Pauliny J, Lipper EG, Bussel JB. Long-term effects of fetal and neonatal alloimmune thrombocytopenia and its antenatal treatment on the medical and developmental outcomes of affected children. Am J Perinatol 2006; 23:487.
  46. Tiller H, Kamphuis MM, Flodmark O, et al. Fetal intracranial haemorrhages caused by fetal and neonatal alloimmune thrombocytopenia: an observational cohort study of 43 cases from an international multicentre registry. BMJ Open 2013; 3.