Fetale und neonatale Alloimmunthrombozytopenie, Teil 1

Zusammenfassung

Die fetale und neonatale Alloimmunthrombozytopenie (FNAIT) wird durch mütterliche Antikörper hervorgerufen, die gegen ein vom Vater ererbtes Blutgruppenmerkmal an fetalen Thrombozyten gerichtet sind. Teil 1 des Beitrags stellt die Ätiologie, die Pathogenese und die Diagnostik der FNAIT dar, während Teil 2 die Risikostratifizierung und Behandlung der FNAIT thematisiert [1].

Abstract

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding condition caused by maternal antibodies against fetal platelet antigens inherited from the father. The incidence of severe FNAIT (neonatal platelet count < 50 G/l) is 1 in 2500 live births. Its most severe consequence, intracranial hemorrhage, leading to death or neurologic disability, occurs in 10 per 100 000 neonates, commonly prior to birth. This review summarizes the current knowledge on incidence, pathogenesis, diagnosis of FNAIT in this part 1 followed by the management of pregnancies at risk and prophylaxis in part 2.

Schlüsselwörter

fetale und neonatale Alloimmunthrombozytopenie - FNAIT - neonatale Thrombozytopenie - nichtinvasive Pränataldiagnostik

Key words

fetal and neonatal alloimmune thrombocytopenia - FNAIT - neonatal thrombocytopenia - non-invasive prenatal diagnosis

• Literatur

• 1 Sachs UJ, Bedei I, Wienzek-Lischka S. et al. Fetale und neonatale Alloimmunthrombozytopenie, Teil 2: Risikostratifizierung und Behandlung. Transfusionsmedizin 2021; 11: 127-142
• 2 Baker JM, Shehata N, Bussel J. et al. Postnatal intervention for the treatment of FNAIT: a systematic review. J Perinatol 2019; 39: 1329-1339
• 3 Philipps Universität Marburg. Dohrn, Hans Heinrich Alfred Rudolf. Professorenkatalog der Philipps-Universität Marburg. Im Internet (Stand: 14.02.2021): https://professorenkatalog.online.uni-marburg.de/de/pkat/idrec?id=10487
• 4 Dohrn R. Ein Fall von Morbus maculosus Werlhofii übertragen von der Mutter auf die Frucht. Arch Gynäkol 1874; 6: 486-487
• 5 Harrington WJ, Sprague CC, Minnich V. et al. Immunologic mechanisms in idiopathic and neonatal thrombocytopenic purpura. Ann Intern Med 1953; 38: 433-469
• 6 van Loghem JJ J, Dorfmeijer H, van Hart M. et al. Serological and genetical studies on a platelet antigen (Zw). Vox Sang 1959; 4: 161-169
• 7 Shulman NR, Aster RH, Leitner A. et al. 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: 1597-1620
• 8 Shulman NR, Aster RH, Pearson HA. et al. Immunoreactions involving platelet. VI. Reactions of maternal isoantibodies responsible for neonatal purpura. Differentiation of a second platelet antigen system. J Clin Invest 1962; 41: 1059-1069
• 9 Kamphuis MM, Paridaans NP, Porcelijn L. et al. Incidence and consequences of neonatal alloimmune thrombocytopenia: a systematic review. Pediatrics 2014; 133: 715-721
• 10 Kamphuis MM, Paridaans N, Porcelijn L. et al. Screening in pregnancy for fetal or neonatal alloimmune thrombocytopenia: systematic review. BJOG 2010; 117: 1335-1343
• 11 Davoren A, McParland P, Barnes CA. et al. Neonatal alloimmune thrombocytopenia in the Irish population: a discrepancy between observed and expected cases. J Clin Pathol 2002; 55: 289-292
• 12 Sachs UJ, Wienzek-Lischka S, Duong Y. et al. Maternal antibodies against paternal class I human leukocyte antigens are not associated with foetal and neonatal alloimmune thrombocytopenia. Br J Haematol 2020; 189: 751-759
• 13 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
• 14 Versiti. HPA Database (Oktober 2020). Im Internet (Stand: 13.05.2021): https://www.versiti.org/hpa
• 15 Ghevaert C, Campbell K, Walton J. et al. Management and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia. Transfusion 2007; 47: 901-910
• 16 Kroll H, Yates J, Santoso S. Immunization against a low-frequency human platelet alloantigen in fetal alloimmune thrombocytopenia is not a single event: characterization by the combined use of reference DNA and novel allele-specific cell lines expressing recombinant antigens. Transfusion 2005; 45: 353-358
• 17 Davoren A, Curtis BR, Aster RH. et al. Human platelet antigen-specific alloantibodies implicated in 1162 cases of neonatal alloimmune thrombocytopenia. Transfusion 2004; 44: 1220-1225
• 18 Ohto H, Miura S, Ariga H. et al. The natural history of maternal immunization against foetal platelet alloantigens. Transfus Med 2004; 14: 399-408
• 19 Tomiyama Y, Take H, Ikeda H. et al. Identification of the platelet-specific alloantigen, Naka, on platelet membrane glycoprotein IV. Blood 1990; 75: 684-687
• 20 Curtis BR, Aster RH. Incidence of the Nak(a)-negative platelet phenotype in African Americans is similar to that of Asians. Transfusion 1996; 36: 331-334
• 21 Mueller-Eckhardt C, Kiefel V, Grubert A. et al. 348 cases of suspected neonatal alloimmune thrombocytopenia. Lancet 1989; 1: 363-366
• 22 Jin JC, Lakkaraja MM, Ferd P. et al. Maternal sensitization occurs before delivery in severe cases of fetal alloimmune thrombocytopenia. Am J Hematol 2019; 94: E213-E215
• 23 Gruel Y, Boizard B, Daffos F. et al. Determination of platelet antigens and glycoproteins in the human fetus. Blood 1986; 68: 488-492
• 24 Bennett JS. Structure and function of the platelet integrin alphaIIbbeta3. J Clin Invest 2005; 115: 3363-3369
• 25 Kumpel BM, Sibley K, Jackson DJ. et al. Ultrastructural localization of glycoprotein III a (GPIIIa, β3 integrin) on placental syncytiotrophoblast microvilli: implications for platelet alloimmunization during pregnancy. Transfusion 2008; 48: 2077-2086
• 26 Kjeldsen-Kragh J, Ahlen MT. Foetal and neonatal alloimmune thrombocytopenia – The role of the HLA-DRB3*01:01 allele for HPA-1a-immunisation and foetal/neonatal outcome. Transfus Apher Sci 2020; 59: 102707
• 27 Newman PJ, Derbes RS, Aster RH. The human platelet alloantigens, PlA1 and PlA2, are associated with a leucine33/proline33 amino acid polymorphism in membrane glycoprotein III a, and are distinguishable by DNA typing. J Clin Invest 1989; 83: 1778-1781
• 28 Anani Sarab G, Moss M, Barker RN. et al. Naturally processed peptides spanning the HPA-1a polymorphism are efficiently generated and displayed from platelet glycoprotein by HLA-DRB3*0101-positive antigen-presenting cells. Blood 2009; 114: 1954-1957
• 29 Wienzek-Lischka S, König IR, Papenkort E-M. et al. HLA-DRB3*01:01 is a predictor of immunization against human platelet antigen-1a but not of the severity of fetal and neonatal alloimmune thrombocytopenia. Transfusion 2017; 57: 533-540
• 30 Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 2007; 7: 715-725
• 31 Palmeira P, Quinello C, Silveira-Lessa AL. et al. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol 2012; 2012: 985646
• 32 Santoso S, Wihadmadyatami H, Bakchoul T. et al. Antiendothelial αvβ3 Antibodies Are a Major Cause of Intracranial Bleeding in Fetal/Neonatal Alloimmune Thrombocytopenia. Arterioscler Thromb Vasc Biol 2016; 36: 1517-1524
• 33 Panzer S, Auerbach L, Cechova E. et al. Maternal alloimmunization against fetal platelet antigens: a prospective study. Br J Haematol 1995; 90: 655-660
• 34 Sellers J, Thompson J, Guttridge MG. et al. Human platelet antigens: typing by PCR using sequence-specific primers and their distribution in blood donors resident in Wales. Eur J Immunogenet 1999; 26: 393-397
• 35 Schnaidt M, Wernet D. Platelet-specific antibodies in female blood donors after pregnancy. Transfus Med 2000; 10: 77-80
• 36 Kaplan C, Morel-Kopp MC, Kroll H. et al. HPA-5b (Br(a)) neonatal alloimmune thrombocytopenia: clinical and immunological analysis of 39 cases. Br J Haematol 1991; 78: 425-429
• 37 Taaning E. HLA antibodies and fetomaternal alloimmune thrombocytopenia: myth or meaningful?. Transfus Med Rev 2000; 14: 275-280
• 38 Curtis BR, Fick A, Lochowicz AJ. et al. Neonatal alloimmune thrombocytopenia associated with maternal-fetal incompatibility for blood group B. Transfusion 2008; 48: 358-364
• 39 Vos TW de Winkelhorst D. et al. Haas M de et al. Epidemiology and management of fetal and neonatal alloimmune thrombocytopenia. Transfus Apher Sci 2020; 59: 102704
• 40 Tiller H, Killie MK, Husebekk A. et al. Platelet antibodies and fetal growth: maternal antibodies against fetal platelet antigen 1a are strongly associated with reduced birthweight in boys. Acta Obstet Gynecol Scand 2012; 91: 79-86
• 41 Delbos F, Bertrand G, Croisille L. et al. Fetal and neonatal alloimmune thrombocytopenia: predictive factors of intracranial hemorrhage. Transfusion 2016; 56: 59-66 quiz 58
• 42 Bussel JB, Zacharoulis S, Kramer K. et al. Clinical and diagnostic comparison of neonatal alloimmune thrombocytopenia to non-immune cases of thrombocytopenia. Pediatr Blood Cancer 2005; 45: 176-183
• 43 Winkelhorst D, Kamphuis MM, Steggerda SJ. et al. Perinatal outcome and long-term neurodevelopment after intracranial haemorrhage due to fetal and neonatal alloimmune thrombocytopenia. Fetal Diagn Ther 2019; 45: 184-191
• 44 Bonacossa IA, Jocelyn LJ. Alloimmune thrombocytopenia of the newborn: neurodevelopmental sequelae. Am J Perinatol 1996; 13: 211-215
• 45 Radder CM, Brand A, Kanhai HHH. Will it ever be possible to balance the risk of intracranial haemorrhage in fetal or neonatal alloimmune thrombocytopenia against the risk of treatment strategies to prevent it?. Vox Sang 2003; 84: 318-325
• 46 Dubruc E, Lebreton F, Giannoli C. et al. Placental histological lesions in fetal and neonatal alloimmune thrombocytopenia: A retrospective cohort study of 21 cases. Placenta 2016; 48: 104-109
• 47 Kiefel V, Santoso S, Weisheit M. et al. Monoclonal antibody – specific immobilization of platelet antigens (MAIPA): a new tool for the identification of platelet-reactive antibodies. Blood 1987; 70: 1722-1726
• 48 Campbell K, Rishi K, Howkins G. et al. A modified rapid monoclonal antibody-specific immobilization of platelet antigen assay for the detection of human platelet antigen (HPA) antibodies: a multicentre evaluation. Vox Sang 2007; 93: 289-297
• 49 Menitove JE, Pereira J, Hoffman R. et al. Cyclic thrombocytopenia of apparent autoimmune etiology. Blood 1989; 73: 1561-1569
• 50 Nguyen XD, Goebel M, Schober M. et al. The detection of platelet antibodies by simultaneous analysis of specific platelet antibodies and the monoclonal antibody-specific immobilization of platelet antigens: an interlaboratory comparison. Transfusion 2010; 50: 1429-1434
• 51 Uhrynowska M, Maslanka K, Zupanska B. Neonatal thrombocytopenia: incidence, serological and clinical observations. Am J Perinatol 1997; 14: 415-418
• 52 Porcelijn L, Huiskes E, Comijs-van Osselen I. et al. A new bead-based human platelet antigen antibodies detection assay versus the monoclonal antibody immobilization of platelet antigens assay. Transfusion 2014; 54: 1486-1492
• 53 Cooper N, Bein G, Heidinger K. et al. A bead-based assay in the work-up of suspected platelet alloimmunization. Transfusion 2016; 56: 115-118
• 54 Holzwarth ST, Strobel J, Cooper N. et al. A point mutation c.473A G of ITGB3 is responsible for the formation of the Woa human platelet alloantigen. Transfusion 2020; 60: E5-E6
• 55 Petermann R, Bakchoul T, Curtis BR. et al. Investigations for fetal and neonatal alloimmune thrombocytopenia: communication from the SSC of the ISTH. J Thromb Haemost 2018; 16: 2526-2529
• 56 Bakchoul T, Kubiak S, Krautwurst A. 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: 2455-2461
• 57 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: 1309-1318
• 58 Socher I, Zwingel C, Santoso S. et al. Heterogeneity of HPA-3 alloantibodies: consequences for the diagnosis of alloimmune thrombocytopenic syndromes. Transfusion 2008; 48: 463-472
• 59 Harrison CR, Curtis BR, McFarland JG. et al. Severe neonatal alloimmune thrombocytopenia caused by antibodies to human platelet antigen 3a (Baka) detectable only in whole platelet assays. Transfusion 2003; 43: 1398-1402
• 60 Ertel K, Al-Tawil M, Santoso S. et al. Relevance of the HPA-15 (Gov) polymorphism on CD109 in alloimmune thrombocytopenic syndromes. Transfusion 2005; 45: 366-373
• 61 Schallmoser K, Kutschera J, Macher S. et al. Delayed detectability of anti-HPA-3a by the MAIPA assay in a severe neonatal alloimmune thrombocytopenia, but successful transfusion of incompatible donor platelets: a case report. Vox Sang 2006; 91: 181-183