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Fetal and Neonatal Alloimmune Thrombocytopenia

  • Justin Juskewitch
  • Jeffrey L. Winters
Chapter

Abstract

Fetal and neonatal alloimmune thrombocytopenia [FNAIT] is a rare but potentially devastating condition that occurs when mothers form alloantibodies to paternally inherited fetal platelet antigens (often members of a human platelet antigen group). Unlike hemolytic disease of the newborn and fetus due to maternal erythrocyte alloantibodies, FNAIT commonly occurs during a mother’s very first pregnancy and thus is not realized until the birth of an affected child. Affected fetuses and neonates can suffer from mucocutaneous bleeding, intracranial hemorrhage, and even death. These same anti-platelet alloantibodies can also cause post-transfusion purpura, a rare transfusion reaction that causes isolated, unexplained, and profound thrombocytopenia several days after a blood transfusion (usually after receiving a non-platelet blood product). Post-transfusion purpura also inexplicably involves the destruction of the recipient’s own native platelets and has a 5–10% mortality rate from bleeding complications.

Keywords

Alloimmune thrombocytopenia Neonate Fetus Post-transfusion purpura Human platelet antigens 

References

  1. 1.
    Mueller-Eckhardt C, Kiefel V, Grubert A. High-dose IgG treatment for neonatal alloimmune thrombocytopenia. Blut. 1989;59(1):145–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Bassler D, Greinacher A, Okascharoen C, Klenner A, Ditomasso J, Kiefel V, et al. A systematic review and survey of the management of unexpected neonatal alloimmune thrombocytopenia. Transfusion. 2008;48(1):92–8.  https://doi.org/10.1111/j.1537-2995.2007.01486.x. CrossRefPubMedGoogle Scholar
  3. 3.
    Davoren A, McParland P, Crowley J, Barnes A, Kelly G, Murphy WG. Antenatal screening for human platelet antigen-1a: results of a prospective study at a large maternity hospital in Ireland. BJOG. 2003;110(5):492–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Kjeldsen-Kragh J, Killie MK, Tomter G, Golebiowska E, Randen I, Hauge R, et al. A screening and intervention program aimed to reduce mortality and serious morbidity associated with severe neonatal alloimmune thrombocytopenia. Blood. 2007;110(3):833–9.  https://doi.org/10.1182/blood-2006-08-040121.CrossRefPubMedGoogle Scholar
  5. 5.
    Tiller H, Killie MK, Skogen B, Oian P, Husebekk A. Neonatal alloimmune thrombocytopenia in Norway: poor detection rate with nonscreening versus a general screening programme. BJOG. 2009;116(4):594–8.  https://doi.org/10.1111/j.1471-0528.2008.02068.x.CrossRefPubMedGoogle Scholar
  6. 6.
    Saito S, Ota M, Komatsu Y, Ota S, Aoki S, Koike K, et al. Serologic analysis of three cases of neonatal alloimmune thrombocytopenia associated with HLA antibodies. Transfusion. 2003;43(7):908–17.CrossRefPubMedGoogle Scholar
  7. 7.
    Curtis BR, Fick A, Lochowicz AJ, McFarland JG, Ball RH, Peterson J, et al. Neonatal alloimmune thrombocytopenia associated with maternal-fetal incompatibility for blood group B. Transfusion. 2008;48(2):358–64.  https://doi.org/10.1111/j.1537-2995.2007.01531.x. CrossRefPubMedGoogle Scholar
  8. 8.
    Kato S, Sugiura T, Ueda H, Ito K, Kakita H, Kato I, et al. Massive intracranial hemorrhage caused by neonatal alloimmune thrombocytopenia associated with anti-group A antibody. J Perinatol. 2013;33(1):79–82.  https://doi.org/10.1038/jp.2011.204.CrossRefPubMedGoogle Scholar
  9. 9.
    European Bioinformatics Institute. Immuno polymorphism database. Cambridge, United Kingdom. 2017. http://www.ebi.ac.uk/ipd/hpa/table1.html. Accessed 25 Aug 2017.
  10. 10.
    Mueller-Eckhardt C, Kiefel V, Grubert A, Kroll H, Weisheit M, Schmidt S, et al. 348 cases of suspected neonatal alloimmune thrombocytopenia. Lancet. 1989;1(8634):363–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Bussel JB, Zabusky MR, Berkowitz RL, McFarland JG. Fetal alloimmune thrombocytopenia. N Engl J Med. 1997;337(1):22–6.  https://doi.org/10.1056/NEJM199707033370104.CrossRefPubMedGoogle Scholar
  12. 12.
    Bertrand G, Drame M, Martageix C, Kaplan C. Prediction of the fetal status in noninvasive management of alloimmune thrombocytopenia. Blood. 2011;117(11):3209–13.  https://doi.org/10.1182/blood-2010-08-302463.CrossRefPubMedGoogle Scholar
  13. 13.
    Kapur R, Kustiawan I, Vestrheim A, Koeleman CA, Visser R, Einarsdottir HK, et al. A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy. Blood. 2014;123(4):471–80.  https://doi.org/10.1182/blood-2013-09-527978.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Yougbare I, Lang S, Yang H, Chen P, Zhao X, Tai WS, et al. Maternal anti-platelet beta3 integrins impair angiogenesis and cause intracranial hemorrhage. J Clin Invest. 2015;125(4):1545–56.  https://doi.org/10.1172/JCI77820.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Santoso S, Wihadmadyatami H, Bakchoul T, Werth S, Al-Fakhri N, Bein G, et al. Antiendothelial alphavbeta3 antibodies are a major cause of intracranial bleeding in fetal/neonatal alloimmune thrombocytopenia. Arterioscler Thromb Vasc Biol. 2016;36(8):1517–24.  https://doi.org/10.1161/ATVBAHA.116.307281. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Cooper N, Bein G, Heidinger K, Santoso S, Sachs UJ. A bead-based assay in the work-up of suspected platelet alloimmunization. Transfusion. 2016;56(1):115–8.  https://doi.org/10.1111/trf.13351.CrossRefPubMedGoogle Scholar
  17. 17.
    Kiefel V, Bassler D, Kroll H, Paes B, Giers G, Ditomasso J, et al. Antigen-positive platelet transfusion in neonatal alloimmune thrombocytopenia (NAIT). Blood. 2006;107(9):3761–3.  https://doi.org/10.1182/blood-2005-06-2235.CrossRefPubMedGoogle Scholar
  18. 18.
    Tiller H, Kamphuis MM, Flodmark O, Papadogiannakis N, David AL, Sainio S, 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(3):pii: e002490.  https://doi.org/10.1136/bmjopen-2012-002490.CrossRefGoogle Scholar
  19. 19.
    Scheffer PG, Ait Soussan A, Verhagen OJ, Page-Christiaens GC, Oepkes D, de Haas M, et al. Noninvasive fetal genotyping of human platelet antigen-1a. BJOG. 2011;118(11):1392–5.  https://doi.org/10.1111/j.1471-0528.2011.03039.x.CrossRefPubMedGoogle Scholar
  20. 20.
    Bussel JB, Berkowitz RL, Hung C, Kolb EA, Wissert M, Primiani A, et al. Intracranial hemorrhage in alloimmune thrombocytopenia: stratified management to prevent recurrence in the subsequent affected fetus. Am J Obstet Gynecol. 2010;203(2):135.e1–14.  https://doi.org/10.1016/j.ajog.2010.03.011.CrossRefGoogle Scholar
  21. 21.
    Berkowitz RL, Kolb EA, McFarland JG, Wissert M, Primani A, Lesser M, et al. Parallel randomized trials of risk-based therapy for fetal alloimmune thrombocytopenia. Obstet Gynecol. 2006;107(1):91–6.  https://doi.org/10.1097/01.AOG.0000192404.25780.68.CrossRefPubMedGoogle Scholar
  22. 22.
    Rayment R, Brunskill SJ, Soothill PW, Roberts DJ, Bussel JB, Murphy MF. Antenatal interventions for fetomaternal alloimmune thrombocytopenia. Cochrane Database Syst Rev. 2011(5):CD004226.  https://doi.org/10.1002/14651858.CD004226.pub3.
  23. 23.
    Weng YJ, Husebekk A, Skogen B, Kjaer M, Lin LT, Burnouf T. Anti-human platelet antigen-1a immunoglobulin G preparation intended to prevent fetal and neonatal alloimmune thrombocytopenia. PLoS One. 2016;11(9):e0162973.  https://doi.org/10.1371/journal.pone.0162973.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Shulman NR, Aster RH, Leitner A, Hiller MC. A new syndrome of post-transfusion immunologic purpura. J Clin Invest. 1960;1960(39):1028–31.Google Scholar
  25. 25.
    Shulman NR, Aster RH, Leitner A, Hiller MC. Immunoreactions involving platelets. V. Post-transfusion purpura due to a complement-fixing antibody against a genetically controlled platelet antigen. A proposed mechanism for thrombocytopenia and its relevance in “autoimmunity”. J Clin Invest. 1961;40(9):1597–620.  https://doi.org/10.1172/JCI104383.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Lubenow N, Eichler P, Albrecht D, Carlsson LE, Kothmann J, Rossocha WR, et al. Very low platelet counts in post-transfusion purpura falsely diagnosed as heparin-induced thrombocytopenia. Report of four cases and review of literature. Thromb Res. 2000;100(3):115–25.CrossRefPubMedGoogle Scholar
  27. 27.
    Schwartz J, Padmanabhan A, Aqui N, Balogun RA, Connelly-Smith L, Delaney M, et al. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the writing Committee of the American Society for Apheresis: the seventh special issue. J Clin Apher. 2016;31(3):149–62.  https://doi.org/10.1002/jca.21470.CrossRefPubMedGoogle Scholar
  28. 28.
    Williamson LM, Stainsby D, Jones H, Love E, Chapman CE, Navarrete C, et al. The impact of universal leukodepletion of the blood supply on hemovigilance reports of posttransfusion purpura and transfusion-associated graft-versus-host disease. Transfusion. 2007;47(8):1455–67.  https://doi.org/10.1111/j.1537-2995.2007.01281.x.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Transfusion Medicine, Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA

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