Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:

Subscribers log in here

Prenatal management of neonatal alloimmune thrombocytopenia


Neonatal alloimmune thrombocytopenia (NAIT) refers to a disorder in which fetal platelets contain an antigen inherited from the father that the mother lacks. These antibodies cross the placenta and bind to the fetal platelets. Clearance of the antibody-coated platelets results in fetal/neonatal thrombocytopenia.

Antibodies directed against platelet antigen HPA-1a (formerly called PLA-1) account for more than 80 percent of NAIT in Caucasians [1]. Approximately 98 percent of Caucasians express HPA-1a and about 2 percent of women are HPA-1a negative (HPA-1b homozygotes). Immunoglobulin G (IgG) antibodies (anti HPA-1a) are found in about 10 percent of HPA-1a negative pregnant women [2].  

The HPA-5b antigen (formerly the Br antigen) is the second most common platelet antigen causing NAIT in Caucasians. In Asians, the HPA-4 system (formerly called Pen or Yuk) is the most frequent cause of NAIT. More than a dozen other platelet antigens have been associated with NAIT. The prevalence of these antigens varies among different ethnic groups; some antigens are quite rare [3].

The severity of NAIT differs depending on the antigen involved; HPA-1a causes severe disease [1]. Other factors, such as HLA type, can modulate severity of disease in offspring. Vascular endothelial dysfunction has also been implicated in the pathogenesis of NAIT [4,5]. (See "Causes of neonatal thrombocytopenia", section on 'Fetal and neonatal alloimmune thrombocytopenia'.)


The mother of a fetus/newborn with NAIT is asymptomatic.


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2014. | This topic last updated: Jul 26, 2013.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
  1. Bussel JB, Zabusky MR, Berkowitz RL, McFarland JG. Fetal alloimmune thrombocytopenia. N Engl J Med 1997; 337:22.
  2. 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.
  3. 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.
  4. 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.
  5. Kay HH, Hage ML, Kurtzberg J, Dunsmore KP. Alloimmune thrombocytopenia may be associated with systemic disease. Am J Obstet Gynecol 1992; 166:110.
  6. 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.
  7. 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.
  8. Murphy MF, Hambley H, Nicolaides K, Waters AH. Severe fetomaternal alloimmune thrombocytopenia presenting with fetal hydrocephalus. Prenat Diagn 1996; 16:1152.
  9. Mueller-Eckhardt C, Kiefel V, Grubert A, et al. 348 cases of suspected neonatal alloimmune thrombocytopenia. Lancet 1989; 1:363.
  10. Herman JH, Jumbelic MI, Ancona RJ, Kickler TS. In utero cerebral hemorrhage in alloimmune thrombocytopenia. Am J Pediatr Hematol Oncol 1986; 8:312.
  11. 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.
  12. Berkowitz RL, Bussel JB, McFarland JG. Alloimmune thrombocytopenia: state of the art 2006. Am J Obstet Gynecol 2006; 195:907.
  13. 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.
  14. 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.
  15. 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.
  16. Killie MK, Kjeldsen-Kragh J, Husebekk A, et al. Cost-effectiveness of antenatal screening for neonatal alloimmune thrombocytopenia. BJOG 2007; 114:588.
  17. Kamphuis MM, Paridaans N, Porcelijn L, et al. Screening in pregnancy for fetal or neonatal alloimmune thrombocytopenia: systematic review. BJOG 2010; 117:1335.
  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. 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.
  22. 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.
  23. 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.
  24. 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.
  25. Scheffer PG, Ait Soussan A, Verhagen OJ, et al. Noninvasive fetal genotyping of human platelet antigen-1a. BJOG 2011; 118:1392.
  26. 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.
  27. Rayment R, Brunskill SJ, Stanworth S, et al. Antenatal interventions for fetomaternal alloimmune thrombocytopenia. Cochrane Database Syst Rev 2005; :CD004226.
  28. Gaddipati, S, Berkowitz, RL, Lembet, AA, Lapinski, R, McFarland, JG, Bussel, JB. Initial platelet counts predict the response to intravenous gamma globulin therapy in fetuses that are affected by PLA1 incompatibilty. Am J Obstet Gynecol 2006; 107:91.
  29. 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.
  30. 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.
  31. Lynch L, Bussel JB, McFarland JG, et al. Antenatal treatment of alloimmune thrombocytopenia. Obstet Gynecol 1992; 80:67.
  32. Bussel JB, Berkowitz RL, McFarland JG, et al. Antenatal treatment of neonatal alloimmune thrombocytopenia. N Engl J Med 1988; 319:1374.
  33. Berkowitz RL, Kolb EA, McFarland JG, et al. Parallel randomized trials of risk-based therapy for fetal alloimmune thrombocytopenia. Obstet Gynecol 2006; 107:91.
  34. Vinograd CA, Bussel JB. Antenatal treatment of fetal alloimmune thrombocytopenia: a current perspective. Haematologica 2010; 95:1807.
  35. 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.
  36. 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.
  37. 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.
  38. Kamphuis MM, Oepkes D. Fetal and neonatal alloimmune thrombocytopenia: prenatal interventions. Prenat Diagn 2011; 31:712.
  39. Kanhai HH, van den Akker ES, Walther FJ, Brand A. Intravenous immunoglobulins without initial and follow-up cordocentesis in alloimmune fetal and neonatal thrombocytopenia at high risk for intracranial hemorrhage. Fetal Diagn Ther 2006; 21:55.
  40. 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.
  41. Mechoulan A, Kaplan C, Muller JY, et al. Fetal alloimmune thrombocytopenia: is less invasive antenatal management safe? J Matern Fetal Neonatal Med 2011; 24:564.
  42. 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.
  43. Paidas MJ, Berkowitz RL, Lynch L, et al. Alloimmune thrombocytopenia: fetal and neonatal losses related to cordocentesis. Am J Obstet Gynecol 1995; 172:475.
  44. van den Akker E, Oepkes D, Brand A, Kanhai HH. Vaginal delivery for fetuses at risk of alloimmune thrombocytopenia? BJOG 2006; 113:781.
  45. Ghevaert C, Wilcox DA, Fang J, et al. Developing recombinant HPA-1a-specific antibodies with abrogated Fcgamma receptor binding for the treatment of fetomaternal alloimmune thrombocytopenia. J Clin Invest 2008; 118:2929.
  46. Ghevaert C, Herbert N, Hawkins L, et al. Recombinant HPA-1a antibody therapy for treatment of fetomaternal alloimmune thrombocytopenia: proof of principle in human volunteers. Blood 2013; 122:313.
  47. Kaplan C. FNAIT: the fetus pleads guilty! Blood 2010; 116:3384.
  48. Chen P, Li C, Lang S, et al. Animal model of fetal and neonatal immune thrombocytopenia: role of neonatal Fc receptor in the pathogenesis and therapy. Blood 2010; 116:3660.