Fetal and neonatal alloimmune thrombocytopenia: review article and retrospective analysis of clinical and laboratory characteristics of patients in Slovenia between 1996 and 2016

  • Jana Lozar Krivec Neonatal Unit, Division of Paediatrics, University Medical Centre Ljubljana, Ljubljana, Slovenia
  • Tatjana Tanasič Neonatal Unit, Division of Paediatrics, University Medical Centre Ljubljana, Ljubljana, Slovenia
  • Jelena Đorđević Neonatal Unit, Division of Paediatrics, University Medical Centre Ljubljana, Ljubljana, Slovenia
  • Petra Fidler Department of Perinatology, Division of Obstetrics and Gynecology, University Medical Centre Maribor, Maribor, Slovenia
  • Irena Štucin Gantar Department of Perinatology, Division of Obstetrics and Gynecology, University Medical Centre Ljubljana, Ljubljana, Slovenia
  • Andreja Trojner-Bregar Department of Perinatology, Division of Obstetrics and Gynecology, University Medical Centre Ljubljana, Ljubljana, Slovenia
  • Primož Rožman Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia
  • Polona Klemenc Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia
  • Darja Paro-Panjan Neonatal Unit, Division of Paediatrics, University Medical Centre Ljubljana, Ljubljana, Slovenia
Keywords: , alloimmunisation, thrombocytopenia, neonate, pregnancy, human platelet antigen (HPA)


Neonatal alloimmune thrombocytopenia (FNAIT) results from transplacental transmission and binding of alloimmune antibodies on child's platelets antigens which were inherited from the father. Alloimmunization of the mother against platelet antigen can occur during present or previous pregnancies or platelet transfusions. FNAIT is a rare disease whose course can be insignificant or with signs of haemorrhagic diathesis. It's most serious complication is intracranial bleeding, therefore early diagnosis and in the case of indications appropriate treatment is very important. Estimated incidence of FNAIT is 1 in 1000-2000 live births. According to the Slovenia’s national vital statistics data we estimate that there should be between 10 and 20 annually serologically confirmed cases of FNAIT. Incidence of FNAIT in Slovenia is not known. The aim of the present retrospective study was to assess the incidence and aetiology of FNAIT in Slovenia and clinical characteristics of the disease. The results of a retrospective study in which we analysed the results of blood tests for the detection of platelet antibodies in infants or mothers have shown a much lower incidence. In the period from 1996 to 2016 there were in average 9 requests for FNAIT diagnostic tests per year and 39 cases of FNAIT were confirmed, resulting in incidence rate of  0,1/1000 live births in Slovenia. We are aware that obtained incidence may be underestimated due to retrospective analysis of the data; nevertheless our results confirm our clinical observations that FNAIT is underdiagnosed in our area. In the present article in addition to the results of a retrospective study on the incidence, aetiology and clinical picture of FNAIT in Slovenia, we review current knowledge of FNAIT. With this contribution we aim to increase awareness about FNAIT, which can be life-threatening and it’s promptly diagnosis may be very important for the child as well as mother’s following pregnancies.


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Brouk H, Ouelaa H. Fetal and Neonatal Alloimmune Thrombocytopenia: Advances in Laboratory Diagnosis and Management. Int J Blood Res Disord 2:013.

Blanchette VS, Chen L, de Friedberg ZS, Hogan VA, Trudel E, Décary F. Alloimmunization to the PlA1 platelet antigen: results of a prospective study. Br J Haematol. 1990;74(2):209-15.

Williamson LM, Hackett G, Rennie J, Palmer CR, Maciver C, Hadfield R, Hughes D 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(7):2280-7.

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.

Tiller H, Killie MK, Skogen B, Øian P, Husebekk A. Neonatal alloimmune thrombocytopenia in Norway: poor detection rate with nonscreening versus a general screening programme. BJOG. 2009;116(4):594-8.

Knight M, Pierce M, Allen D, Kurinczuk JJ, Spark P, Roberts DJ, et al.. The incidence and outcomes of fetomaternal alloimmune thrombocytopenia: a UK national study using three data sources. Br J Haematol. 2011 Feb;152(4):460-8.

Risson DC, Davies MW, Williams BA. Review of neonatal alloimmune thrombocytopenia. J Paediatr Child Health. 2012;48(9):816-22.

Peterson JA, McFarland JG, Curtis BR, Aster RH. Neonatal alloimmune thrombocytopenia: pathogenesis, diagnosis and management. Br J Haematol. 2013; 161(1):3–14.

Brojer E, Husebekk A, Dębska M, Uhrynowska M, Guz K, Orzińska A et al. Fetal/Neonatal Alloimmune Thrombocytopenia: Pathogenesis, Diagnostics and Prevention. Arch ImmunolTherExp (Warsz). 2016;64(4):279-90.

Espinoza JP, Caradeux J, Norwitz ER, Illanes SE. Fetal and Neonatal Alloimmune Thrombocytopenia. Obstet Gynecol. 2013;6(1):e15–e21.

Kumpel BM, Sibley K, Jackson DJ, White G, Soothill PW. Ultrastructural localization of glycoprotein IIIa (GPIIIa, beta 3 integrin) on placental syncytiotrophoblast microvilli: implications for platelet alloimmunization during pregnancy. Transfusion. 2008;48:2077–86.

Tomičić M, Golubić-Ćepulić B, Ivanković Z, Gojčeta K, Đogić V et al. Neonatalna aloimuna trombocitopenija u Hrvatskoj od 1997 do 2007 godine, Lij. Vjesnik 2008 130:183-186.

Kaplan C. Neonatal alloimmune thrombocytopenia: a 50-year story. Immunohematology. 2007;23(1):9-13.

Tiller H, Husebekk A, Ahlen MT, Stuge TB, Skogen B. Current perspectives on fetal and neonatal alloimmune thrombocytopenia - increasing clinical concerns and new treatment opportunities. Int J Womens Health. 2017 Apr 19;9:223-234.

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(5):901-10.

Kaplan C. Alloimune thrombocytopenia of the fetus in the newborn. Blood 2002;16:69-72.

Hutchinson AL, Dennington PM, Holdsworth R, Downe L. Recurrent HLA-B56 mediated neonatal alloimmune thrombocytopenia with fatal outcomes. Transfus Apher Sci. 2015;52(3):311-3.

Tiller H, Kamphuis MM, Flodmark O, Papadogiannakis N, David AL, SainioS 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; 22:3(3).

Spencer JA, Burrows RF. Feto-maternal alloimmune thrombocytopenia; a literature review and statistical analysis. Aust N Z J Obstet Gynaecol. 2001;41(1):45-55.

Murphhy MF, Bussel JB. Advances in the manegement of alloimune thrombocytopenia. BrJ. Haematol 2007;136:366-78.

Bussel JB, Zabusky MR, Berkowitzn RL, McFarland JG. Fetal Alloimmune Thrombocytopenia. N Engl J Med. 1997; 337:22-6.

Bussel JB. Alloimune thrombocitopenia of the fetus in newborn. Semin Thromb Hemost. 2001;27(3):245-52.

Bussel J. Diagnosis and management of the fetus and neonate with alloimmune thrombocytopenia. J Thromb Haemost. 2009;7 Suppl 1:253-7.

Rožman P. Diagnostika trombocitopenije – trombocitne preiskave v nosečnosti. V: Zdravljenje s krvjo (6 ; 2004 ; Portorož) Transfuzijska medicina v porodništvu, Portorož, Slovenija, 3-4 December 2004, Ljubljana, december 2004.

Heikal NM, Smock KJ. Laboratory testing for platelet antibodies. Am J Hematol. 2013 Sep;88(9):818-21.

Rožman P, Klemenc P. Novosti v laboratorijski diagnostiki imunskih trombocitopenij = New trends in the laboratory diagnosis of immune thrombocytopenias. V: ČERNE, Darko (ur.), SKITEK, Milan (ur.). Raziskovalni dnevi laboratorijske biomedicine : [zbornik predavanj]. Ljubljana: Fakulteta za farmacijo, 2014, str. 34-45.

Altarescu G, Eldar-Geva T, Grisaru-Granovsky S, et al. Preimplantation genetic diagnosis for fetal neonatal alloimmune thrombocytopenia due to antihuman platelet antigen maternal antibodies. Obstet Gynecol. 2012;119(2 Pt 1):338–343

Norfolk D. Handbook of Transfusion Medicine, United Kingdom Blood Services, 5th edition; 2014, p. 119-123.

Kaplan C. Neonatal alloimmune thrombocytopenia. Haematologica. 2008;93:805–7.

Le Toriellec E, Chenet C, Kaplan C. Safe fetal platelet genotyping: new developments. Transfusion. 2013;53(8):1755-62.

Constantinescu S, Zamfirescu V, Vladareanu PR. Fetal and neonatal alloimmune thrombocytopenia. Maedica (Buchar). 2012;7(4):372-6.

Pacheco LD, Berkowitz RL, Moise KJ Jr, Bussel JB, McFarland JG, Saade GR. Fetal and neonatal alloimmune thrombocytopenia: a management algorithm based on risk stratification. Obstetrics and Gynecology. 2011;118:1157–1163.

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.

Killie MK, Husebekk A, Kjeldsen-Kragh J, Skogen B. A prospective study of maternal anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in the newborn. Haematologica. 2008;93(6):870–877.

Killie MK, Kjeldsen-Kragh J, Husebekk A, Skogen B, Olsen JA, Kristiansen IS. Cost-effectiveness of antenatal screening for neonatalalloimmune thrombocytopenia. BJOG. 2007;114:588–595

Rožman P. Platelet antigens. The role of human platelet alloantigens (HPA) in blood transfusion and transplantation. Transpl Immunolo. 2002 Aug;10(2-3):165-81.

Rozman P, Drabbels J, Schipper RF, Doxiadis I, Stein S, Claas FH. Genotyping for human platelet-specific antigens HPA-1, -2, -3, -4 and -5 in the Slovenianpopulation reveals a slightly increased frequency of HPA-1b and HPA-2b as compared to otherEuropean populations. Eur J Immunogenet. 1999;26(4):265-9.

Davoren A, Curtis BR, Aster RH, McFarland JG. Human platelet antigen-specific alloantibodies implicated in 1162 cases of neonatal alloimmune thrombocytopenia. Transfusion. 2004;44(8):1220-5.

Mueller-Eckhardt C, Kiefel V, Grubert A, Kroll H, Weisheit M, Schmidt S et al. 348 cases of suspected neonatal alloimmune neonatal thrombocytopenia. Lancet. 1989 Feb 18;1(8634):363-6.

Refsum E, Mörtberg A, Dahl J, Meinke S, Auvinen MK, Westgren M et al. Characterisation of maternal human leukocyte antigen class I antibodies in suspected foetal and neonatal alloimmune thrombocytopenia. Transfus Med. 2017;27(1):43-51.

Peterson JA, Kanack A, Nayak D, Bougie DW, McFarland JG, Curtis BR et al. Prevalence and clinical significance of low-avidity HPA-1a antibodies in women exposed to HPA-1a during pregnancy. Transfusion. 2013;53(6):1309-18.

Bakchoul T, Kubiak S, Krautwurst A, Roderfeld M, Siebert HC, Bein G et al. Low-avidity anti-HPA-1a alloantibodies are capable of antigen-positive platelet destruction in the NOD/SCID mouse model of alloimmune thrombocytopenia. Transfusion. 2011;51(11):2455-61.

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.

Van Der Lugt NM, Kamphuis MM, Paridaans NP, Figee A, Oepkes D, Walther FJ, et al. Neonatal outcome in alloimmune thrombocytopenia after maternal treatment with intravenous immunoglobulin. Blood Transfus. 2015;13(1):66-71.

How to Cite
Lozar Krivec J, Tanasič T, Đorđević J, Fidler P, Štucin Gantar I, Trojner-Bregar A, Rožman P, Klemenc P, Paro-Panjan D. Fetal and neonatal alloimmune thrombocytopenia: review article and retrospective analysis of clinical and laboratory characteristics of patients in Slovenia between 1996 and 2016. ZdravVestn [Internet]. 18Apr.2019 [cited 17Sep.2019];88(3-4):125-42. Available from: https://vestnik.szd.si/index.php/ZdravVest/article/view/2657