Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Postnatal intervention for the treatment of FNAIT: a systematic review

Journal of Perinatology volume 39, pages 1329–1339 (2019)Cite this article

Subjects

Abstract

Objective

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is associated with life-threatening bleeding. This systematic review of postnatal management of FNAIT examined transfusion of human platelet antigen (HPA) selected or unselected platelets, and/or IVIg on platelet increments, hemorrhage and mortality.

Study design

MEDLINE, EMBASE and Cochrane searches were conducted until 11 May 2018.

Result

Of 754 neonates, 382 received platelet transfusions (51%). HPA-selected platelets resulted in higher platelet increments and longer response times than HPA-unselected platelets. However, unselected platelets generally led to sufficient platelet increments to 30 × 109/L, a level above which intracranial hemorrhage or other life-threatening bleeding rarely occurred. Platelet increments were not improved with the addition of IVIg to platelet transfusion.

Conclusion

Overall, HPA-selected platelet transfusions were more effective than HPA-unselected platelets but unselected platelets were often effective enough to achieve clinical goals. Available studies do not clearly demonstrate a benefit for addition of IVIg to platelet transfusion.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. 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;110:833–9.

    Article  CAS  Google Scholar 

  2. Turner ML, Bessos H, Fagge T, Harkness M, Rentoul F, Seymour J, 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;45:1945–56.

    Article  CAS  Google Scholar 

  3. Williamson LM, Hackett G, Rennie J, Palmer CR, Maciver C, Hadfield R, et al. The natural history of fetomaternal alloimmunization to the platelet-specific antigen HPA-1a (PlA1, Zwa) as determined by antenatal screening. Blood. 1998;92:2280–7.

    CAS  PubMed  Google Scholar 

  4. Arnold DM, Smith JW, Kelton JG. Diagnosis and management of neonatal alloimmune thrombocytopenia. Transfus Med Rev. 2008;22:255–67.

    Article  Google Scholar 

  5. Delbos F, Bertrand G, Croisille L, Ansart-Pirenne H, Bierling P, Kaplan C. Fetal and neonatal alloimmune thrombocytopenia: predictive factors of intracranial hemorrhage. Transfusion. 2016;56:59–66.

    Article  CAS  Google Scholar 

  6. Ghevaert C, Campbell K, Walton J, Smith GA, Allen D, Williamson LM, et al. Management and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia. Transfusion. 2007;47:901–10.

    Article  Google Scholar 

  7. 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:e002490.

    Article  Google Scholar 

  8. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–9.

    Article  Google Scholar 

  9. Fowkes FG, Fulton PM. Critical appraisal of published research: introductory guidelines. BMJ. 1991;302:1136–40.

    Article  CAS  Google Scholar 

  10. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64:383–94.

    Article  Google Scholar 

  11. Mueller-Eckhardt C, Kiefel V, Grubert A, Kroll H, Weisheit M, Schmidt S, et al. 348 cases of suspected neonatal alloimmune thrombocytopenia. Lancet. 1989;1:363–6.

    Article  CAS  Google Scholar 

  12. Mueller-Eckhardt C, Kiefel V, Grubert A. High-dose IgG treatment for neonatal alloimmune thrombocytopenia. Blut. 1989;59:145–6.

    Article  CAS  Google Scholar 

  13. Bussel JB, Zacharoulis S, Kramer K, McFarland JG, Pauliny J, Kaplan C. Clinical and diagnostic comparison of neonatal alloimmune thrombocytopenia to non-immune cases of thrombocytopenia. Pediatr Blood Cancer. 2005;45:176–83.

    Article  Google Scholar 

  14. Allen D, Verjee S, Rees S, Murphy MF, Roberts DJ. Platelet transfusion in neonatal alloimmune thrombocytopenia. Blood. 2007;109:388–9.

    Article  CAS  Google Scholar 

  15. Allen DL, Samol J, Benjamin S, Verjee S, Tusold A, Murphy MF. Survey of the use and clinical effectiveness of HPA-1a/5b-negative platelet concentrates in proven or suspected platelet alloimmunization. Transfus Med. 2004;14:409–17.

    Article  CAS  Google Scholar 

  16. Bakchoul T, Bassler D, Heckmann M, Thiele T, Kiefel V, Gross I, et al. Management of infants born with severe neonatal alloimmune thrombocytopenia: the role of platelet transfusions and intravenous immunoglobulin. Transfusion. 2014;54:640–5.

    Article  CAS  Google Scholar 

  17. Fratellanza G, Fratellanza A, Paesano L, Scarcella A, Safoian A, Misso S, et al. Fetoneonatal alloimmune thrombocytopenia (FNAIT): our experience. Transfus Apher Sci. 2006;35:111–7.

    Article  Google Scholar 

  18. Galea P, Patrick MJ, Goel KM. Isoimmune neonatal thrombocytopenic purpura. Arch Dis Child. 1981;56:112–5.

    Article  CAS  Google Scholar 

  19. Glade-Bender J, McFarland JG, Kaplan C, Porcelijn L, Bussel JB. Anti-HPA-3A induces severe neonatal alloimmune thrombocytopenia. J Pediatr. 2001;138:862–7.

    Article  CAS  Google Scholar 

  20. 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;107:3761–3.

    Article  CAS  Google Scholar 

  21. Lee K, Beaujean F, Bierling P. Treatment of severe fetomaternal alloimmune thrombocytopenia with compatible frozen-thawed platelet concentrates. Br J Haematol. 2002;117:482–3.

    Article  CAS  Google Scholar 

  22. te Pas AB, Lopriore E, van den Akker ES, Oepkes D, Kanhai HH, Brand A, et al. Postnatal management of fetal and neonatal alloimmune thrombocytopenia: the role of matched platelet transfusion and IVIG. Eur J Pediatr. 2007;166:1057–63.

    Article  Google Scholar 

  23. Crighton GL, Scarborough R, McQuilten ZK, Phillips LE, Savoia HF, Williams B, et al. Contemporary management of neonatal alloimmune thrombocytopenia: good outcomes in the intravenous immunoglobulin era: results from the Australian neonatal alloimmune thrombocytopenia registry. J Matern Fetal Neonatal Med. 2017;30:2488–94.

    Article  CAS  Google Scholar 

  24. Singh-Grewal D, Kemp A, Wong M. A prospective study of the immediate and delayed adverse events following intravenous immunoglobulin infusions. Arch Dis Child. 2006;91:651–4.

    Article  CAS  Google Scholar 

  25. Krishnan L, Pathare A. Necrotizing enterocolitis in a term neonate following intravenous immunoglobulin therapy. Indian J Pediatr. 2011;78:743–4.

    Article  Google Scholar 

  26. Luban NL, Wong EC, Henrich Lobo R, Pary P, Duke S. Intravenous immunoglobulin-related hemolysis in patients treated for Kawasaki disease. Transfusion. 2015;55(Suppl 2):S90–4.

    Article  CAS  Google Scholar 

  27. Akman AO, Kara FK, Koksal T, Cakir BC, Karagol C, Sayli T. Association of hemolysis with high dose intravenous immunoglobulin therapy in pediatric patients: an open-label prospective trial. Transfus Apher Sci. 2017;56:531–4.

    Article  Google Scholar 

  28. Khan S, Dore PC, Sewell WA. Intravenous immunoglobulin-induced neutropenia. Pediatr Allergy Immunol. 2010;21:892–3.

    Article  CAS  Google Scholar 

  29. Majer RV, Green PJ. Neutropenia caused by intravenous immunoglobulin. Br Med J. 1988;296:1262.

    Article  CAS  Google Scholar 

  30. Veys PA, Macey MG, Owens CM, Newland AC. Neutropenia following intravenous immunoglobulin. Br Med J. 1988;296:1800.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Elizabeth Uleryk for the search strategy; and Sylvia Torrance and Kimberly Figures for administrative assistance.

International Collaboration for Transfusion Medicine Guidelines (ICTMG)

Shubha Allard, MD, FRCP, FRCP(Path), Barts Health NHS Trust and NHS Blood & Transplant, UK; Celso Bianco, MD, formerly with America’s Blood Centres, USA; Jeannie Callum, BA, MD, FRCPC, CTBS, University of Toronto, Canada; Veerle Compernolle, MD, PhD, Belgian Red Cross, Flanders, Belgium; Dean Fergusson, MHA, PhD, University of Ottawa, Canada; Mark Fung, MD, PhD, University of Vermont Medical Center, USA; Susan Nahirniak, MD, FRCPC, University of Alberta, Canada; Katerina Pavenski, MD, FRCPC, University of Toronto, Canada; Joanne Pink, MBBS, FRACP, FRCPA, Australian Red Cross Blood Service, Australia; Arjuna Ponnampalam, MD, FRCPC, University of Manitoba, Canada; Paolo Rebulla, Ospedale Maggiore Policlinico, Italy; Cynthia So-Osman, Sanquin, Netherlands; Simon J. Stanworth, MA, MRCP, DPhil, FRCPath, University of Oxford, UK; Zbigniew M. Szczepiorkowski, MD, PhD, Dartmouth-Hitchcock Medical Centre, USA; Alan T. Tinmouth, MD, FRCPC, MSc, University of Ottawa, Canada; Erica Wood, MBBS, FRACP, FRCPA, Monash University, Australia.

Author contributions

JMB reviewed the citations, analyzed data, drafted the initial manuscript, and participated in critical revisions of the article. HH reviewed the citations, analyzed data, drafted the initial manuscript, and participated in critical revisions of the article. NS reviewed the citations, extracted data and supported all drafts of the manuscript. ST extracted data and supported all drafts of the manuscript. DL finalized the tables and figures, participated in the interpretation of data, and critical revisions of the article. TB, LL, and EM reviewed citations, participated in the interpretation of data, and critical revisions of the article. JB, MFM, AG, DMA, SB, GB, MK, CK, JK-K, DO, HS and GR participated in the interpretation of data and critical revisions of the article. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Funding

Canadian Blood Services partially funded this study. Canadian Blood Services did not have any role in the design, analysis, and interpretation of the data or preparation, review, and approval of the manuscript.

Author information

Authors and Affiliations

  1. St. Michael’s Hospital and The Hospital for Sick Children, University of Toronto, Toronto, Canada

    Jillian M. Baker

  2. Departments of Medicine and Obstetric Medicine, Mount Sinai Hospital, Toronto, Canada

    Nadine Shehata

  3. Center for Innovation, Canadian Blood Services, Toronto, Canada

    Nadine Shehata & Susano Tanael

  4. Weill Cornell Medicine, New York, NY, USA

    James Bussel

  5. NHS Blood & Transplant, Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford University Hospitals and University of Oxford, Oxford, UK

    Michael F. Murphy

  6. Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany

    Andreas Greinacher & Tamam Bakchoul

  7. University Hospital of Tuebingen, Tuebingen, Germany

    Tamam Bakchoul

  8. Diagnostic and Therapeutic Services, NHS Blood and Transplant, Bristol, UK

    Edwin Massey

  9. University Health Network, University of Toronto, Toronto, Canada

    Lani Lieberman

  10. Center for Innovation, Canadian Blood Services, Ottawa, Canada

    Denise Landry

  11. McMaster Centre for Transfusion Research, McMaster University and Canadian Blood Services, Hamilton, Canada

    Donald M. Arnold

  12. Australian Red Cross Blood Service, Brisbane, QLD, Australia

    Shoma Baidya

  13. BloodCenter of Brittany - (EFS) Établissement Français du Sang, Rennes, France

    Gerald Bertrand

  14. Finnmark Hospital Trust, Hammerfest, Norway

    Mette Kjaer

  15. University Hospital of North Norway, Tromsø, Norway

    Mette Kjaer & Jens Kjeldsen-Kragh

  16. Retired and formerly Institut National de la Transfusion Sanguine, Paris, France

    Cécile Kaplan

  17. University and Regional Laboratories Region Skåne, Lund, Sweden

    Jens Kjeldsen-Kragh

  18. Leiden University Medical Center, Leiden, The Netherlands

    Dick Oepkes

  19. Royal Children’s Hospital, Melbourne, Australia

    Helen Savoia

  20. Mount Sinai Hospital, Toronto, Canada

    Greg Ryan

  21. Division of Haematology/Oncology, CHU Sainte-Justine, University of Montreal, Montreal, Canada

    Heather Hume

Authors
  1. Jillian M. Baker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nadine Shehata
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James Bussel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael F. Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andreas Greinacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tamam Bakchoul
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Edwin Massey
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lani Lieberman
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Denise Landry
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Susano Tanael
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Donald M. Arnold
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shoma Baidya
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Gerald Bertrand
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Mette Kjaer
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Cécile Kaplan
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Jens Kjeldsen-Kragh
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Dick Oepkes
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Helen Savoia
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Greg Ryan
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Heather Hume
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the International Collaboration for Transfusion Medicine Guidelines (ICTMG)

  • Shubha Allard
  • , Celso Bianco
  • , Jeannie Callum
  • , Veerle Compernolle
  • , Dean Fergusson
  • , Mark Fung
  • , Susan Nahirniak
  • , Katerina Pavenski
  • , Joanne Pink
  • , Arjuna Ponnampalam
  • , Paolo Rebulla
  • , Cynthia So-Osman
  • , Simon J. Stanworth
  • , Zbigniew M. Szczepiorkowski
  • , Alan T. Tinmouth
  •  & Erica Wood

Corresponding author

Correspondence to Jillian M. Baker.

Ethics declarations

Conflict of interest

MK and JK-K are two of the founders and owners of Prophylix Pharma AS, a Norwegian biotech company coordinating the EU-funded PROFNAIT Consortium which is developing a prophylaxis against fetal and neonatal alloimmune thrombocytopenia (FNAIT). DO has received research funding to a project “Towards routine HPA-screening in Pregnancy”. NS and DMA are consultants for Canadian Blood Services. J Bussel is a consultant of Baxalta, Superior Biologics and Prophylix Pharma. The remaining authors report no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Members of the International Collaboration for Transfusion Medicine Guidelines (ICTMG) are listed below the Acknowledgements.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baker, J.M., Shehata, N., Bussel, J. et al. Postnatal intervention for the treatment of FNAIT: a systematic review. J Perinatol 39, 1329–1339 (2019). https://doi.org/10.1038/s41372-019-0360-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-019-0360-7

Search

Advanced search

Quick links