Diagnostik und Therapie einer Anti-CD36-induzierten neonatalen Alloimmunthrombozytopenie

Zusammenfassung

Mütterliche Antikörper gegen das HPA-1a auf kindlichen Thrombozyten sind der Hauptverursacher einer fetalen oder neonatalen Alloimmunthrombozytopenie (FNAIT). In asiatischen Populationen wurden wiederholt Isoantikörper gegen CD36 als ursächlich im Zusammenhang mit der FNAIT beschrieben, wohingegen in Mitteleuropa die CD36-Defizienz und damit die Möglichkeit einer Immunisierung praktisch unbekannt sind. Das erschwert deutlich die Transfusion mit kompatiblen Thrombozyten bei FNAIT-Fällen, z. B. bei Neugeborenen asiatischer Abstammung. Bei einem Neugeborenen arabischstämmiger Eltern wurde eine Anti-CD36-induzierte FNAIT diagnostiziert. Die Thrombozytenwerte konnten erfolgreich durch die Gabe HPA-unausgewählter Apheresethrombozytenkonzentrate (ATK) stabilisiert werden. Durch ein vorangegangenes Forschungsprojekt zum CD36-Screening bei Blutspendern arabischer Herkunft stand zusätzlich kurz darauf ein ATK mit sehr schwacher CD36-Expression zur Verfügung, das aber nicht mehr benötigt wurde. Dieser Fall weist somit alternative Therapiemöglichkeiten bei einer Anti-CD36-induzierten FNAIT auf.

Abstract

Maternal antibodies to HPA-1a on platelets of the child are the main cause of fetal or neonatal alloimmune thrombocytopenia (FNAIT). In Asian populations isoantibodies to CD36 have been described repeatedly as causative for FNAIT whereas CD36 deficiency and thus the chance to get immunized are virtually unknown in middle European countries. This circumstance aggravates the transfusion of compatible platelets in FNAIT, e.g. in newborns of Asian ancestry. A newborn of Arabian origin was diagnosed with an anti-CD36 induced FNAIT. Platelet counts could be successfully stabilized by transfusion of HPA unselected apheresis platelets. As a result of an earlier research project on a CD36 screening within Arabian blood donors, additionally a platelet concentrate with very weak CD36 expression was available shortly thereafter but was not needed any longer. This case demonstrates alternative therapeutic approaches in CD36 induced FNAIT.

Schlüsselwörter

fetale/neonatale Alloimmunthrombozytopenie (FNAIT) - CD36-spezifischer Isoantikörper - Mutter-Kind-Unverträglichkeit

Key words

fetal/neonatal alloimmune thrombocytopenia (FNAIT) - CD36-specific iso-antibody - feto-maternal incompatibility

Publikationsverlauf

Artikel online veröffentlicht:
27. August 2021

• Literatur

• 1 Lieberman L, Greinacher A, Murphy MF. et al. Fetal and neonatal alloimmune thrombocytopenia: recommendations for evidence-based practice, an international approach. Br J Haematol 2019; 185: 549-562
• 2 Kaplan C. Alloimmune thrombocytopenia of the fetus and the newborn. Blood Rev 2002; 16: 69-72
• 3 Bussel J. Diagnosis and management of the fetus and neonate with alloimmune thrombocytopenia. J Thromb Haemost 2009; 7 (Suppl. 01) 253-257
• 4 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: 2280-2287
• 5 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
• 6 Mueller-Eckhardt C, Kiefel V, Grubert A. et al. 348 cases of suspected neonatal alloimmune thrombocytopenia. Lancet 1989; 1: 363-366
• 7 Mandelbaum M, Koren D, Eichelberger B. et al. Frequencies of maternal platelet alloantibodies and autoantibodies in suspected fetal/neonatal alloimmune thrombocytopenia, with emphasis on human platelet antigen-15 alloimmunization. Vox Sang 2005; 89: 39-43
• 8 Peterson JA, McFarland JG, Curtis BR. et al. Neonatal alloimmune thrombocytopenia: pathogenesis, diagnosis and management. Br J Haematol 2013; 161: 3-14
• 9 Kjeldsen-Kragh J, Bengtsson J. Fetal and Neonatal Alloimmune Thrombocytopenia-New Prospects for Fetal Risk Assessment of HPA-1a-Negative Pregnant Women. Transfus Med Rev 2020; 34: 270-276
• 10 Maslanka K, Yassai M, Gorski J. Molecular identification of T cells that respond in a primary bulk culture to a peptide derived from a platelet glycoprotein implicated in neonatal alloimmune thrombocytopenia. J Clin Invest 1996; 98: 1802-1808
• 11 Wienzek-Lischka S, Konig IR, Papenkort EM. 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
• 12 Greenwalt DE, Lipsky RH, Ockenhouse CF. et al. Membrane glycoprotein CD36: a review of its roles in adherence, signal transduction, and transfusion medicine. Blood 1992; 80: 1105-1115
• 13 Rac ME, Safranow K, Poncyljusz W. Molecular basis of human CD36 gene mutations. Mol Med 2007; 13: 288-296
• 14 Kashiwagi H, Tomiyama Y, Kosugi S. et al. Family studies of type II CD36 deficient subjects: linkage of a CD36 allele to a platelet-specific mRNA expression defect(s) causing type II CD36 deficiency. Thromb Haemost 1995; 74: 758-763
• 15 Yamamoto N, Akamatsu N, Sakuraba H. et al. Platelet glycoprotein IV (CD36) deficiency is associated with the absence (type I) or the presence (type II) of glycoprotein IV on monocytes. Blood 1994; 83: 392-397
• 16 Li R, Qiao Z, Ling B. et al. Incidence and molecular basis of CD36 deficiency in Shanghai population. Transfusion 2015; 55: 666-673
• 17 Phuangtham R, Santoso S, Leelayuwat C. et al. Frequency of CD36 deficiency in Thais analyzed by quantification of CD36 on cell surfaces and in plasma. Transfusion 2020; 60: 847-854
• 18 Imai M, Tanaka T, Kintaka T. et al. Genomic heterogeneity of type II CD36 deficiency. Clin Chim Acta 2002; 321: 97-106
• 19 Lee K, Godeau B, Fromont P. et al. CD36 deficiency is frequent and can cause platelet immunization in Africans. Transfusion 1999; 39: 873-879
• 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 Flesch BK, Scherer V, Opitz A. et al. Platelet CD36 deficiency is present in 2.6 % of Arabian individuals and can cause NAIT and platelet refractoriness. Transfusion 2021; DOI: 10.1111/trf.16398.
• 22 Curtis BR, Ali S, Glazier AM. et al. Isoimmunization against CD36 (glycoprotein IV): description of four cases of neonatal isoimmune thrombocytopenia and brief review of the literature. Transfusion 2002; 42: 1173-1179
• 23 Andersen M, Lenhard B, Whatling C. et al. Alternative promoter usage of the membrane glycoprotein CD36. BMC Mol Biol 2006; 7: 8
• 24 Xu X, Liu Y, Hong X. et al. Variants of CD36 gene and their association with CD36 protein expression in platelets. Blood Transfus 2014; 12: 557-564
• 25 Wu Y, Chen D, Xu X. et al. Hydrops fetalis associated with anti-CD36 antibodies in fetal and neonatal alloimmune thrombocytopenia: Possible underlying mechanism. Transfus Med 2020; 30: 361-368
• 26 Lin M, Xu X, Lee HL. et al. Fetal/neonatal alloimmune thrombocytopenia due to anti-CD36 antibodies: antibody evaluations by CD36-transfected cell lines. Transfusion 2018; 58: 189-195
• 27 Okajima S, Cho K, Chiba H. et al. Two sibling cases of hydrops fetalis due to alloimmune anti-CD36 (Nak a) antibody. Thromb Haemost 2006; 95: 267-271
• 28 Kankirawatana S, Kupatawintu P, Juji T. et al. Neonatal alloimmune thrombocytopenia due to anti-Nak(a). Transfusion 2001; 41: 375-377
• 29 Flesch BK, Scherer V, Just B. et al. Molecular Blood Groups Screening in Donors from Arabian Countries and Iran Using High-Throughput MALD-TOF Mass Spectrometry and PCR-SSP. Trans Med Hemother 2020; 47: 396-408
• 30 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
• 31 Lo SC, Lin KH, Hsieh HH. et al. Genetic variations of CD36 and low platelet CD36 expression – a risk factor for lipemic plasma donation in Taiwanese apheresis donors. Vox Sang 2016; 110: 236-243
• 32 Bundesärztekammer. Richtlinie zur Gewinnung von Blut und Blutbestandteilen und zur Anwendung von Blutprodukten (Richtlinie Hämotherapie). Köln: Deutscher Ärzteverlag; 2017
• 33 Allen DL, Samol J, Benjamin S. et al. Survey of the use and clinical effectiveness of HPA-1a/5b-negative platelet concentrates in proven or suspected platelet alloimmunization. Transfus Med 2004; 14: 409-417
• 34 Kiefel V, Bassler D, Kroll H. et al. Antigen-positive platelet transfusion in neonatal alloimmune thrombocytopenia (NAIT). Blood 2006; 107: 3761-3763
• 35 Flesch B, Miller J, Repp R. et al. Successful autologous hematopoietic progenitor cell transplantation in a patient with an isoantibody against CD36 (glycoprotein IV, Naka). Bone Marrow Transplant 2008; 42: 489-491
• 36 Panzer S. Controversy: HLA antibodies responsible for fetal/neonatal alloimmune thrombocytopenia – an update. Transfus Med Hemother 2006; 33: 495-500
• 37 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
• 38 Dahl J, Skogen B, Kjaer M. et al. A combined effect of anti-HPA-1a and anti-HLA Class I in pregnancy?. Transfusion 2020; 60: 2121-2129
• 39 Khatri SS, Curtis BR, Yamada C. A case of platelet transfusion refractoriness due to anti-CD36 with a successful treatment outcome. Immunohematology 2019; 35: 139-144