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The first two cases of neonatal alloimmune thrombocytopenia associated with the low-frequency platelet antigen HPA-21bw (Nos) in Japan

Authors

  • Yangsook Koh,

    1. From the Japanese Red Cross Osaka Blood Center, Osaka, Japan; the Department of Pediatrics, Saiseikai Shiga-ken Hospital, Shiga, Japan; and the Department of Pediatrics, Osaka Berland Hospital, Osaka, Japan.
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  • Hiroyuki Ishii,

    1. From the Japanese Red Cross Osaka Blood Center, Osaka, Japan; the Department of Pediatrics, Saiseikai Shiga-ken Hospital, Shiga, Japan; and the Department of Pediatrics, Osaka Berland Hospital, Osaka, Japan.
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  • Etsuko Amakishi,

    1. From the Japanese Red Cross Osaka Blood Center, Osaka, Japan; the Department of Pediatrics, Saiseikai Shiga-ken Hospital, Shiga, Japan; and the Department of Pediatrics, Osaka Berland Hospital, Osaka, Japan.
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  • Tomoya Hayashi,

    1. From the Japanese Red Cross Osaka Blood Center, Osaka, Japan; the Department of Pediatrics, Saiseikai Shiga-ken Hospital, Shiga, Japan; and the Department of Pediatrics, Osaka Berland Hospital, Osaka, Japan.
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  • Nobuki Matsuyama,

    1. From the Japanese Red Cross Osaka Blood Center, Osaka, Japan; the Department of Pediatrics, Saiseikai Shiga-ken Hospital, Shiga, Japan; and the Department of Pediatrics, Osaka Berland Hospital, Osaka, Japan.
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  • Yasuo Fukumori,

    Corresponding author
    1. From the Japanese Red Cross Osaka Blood Center, Osaka, Japan; the Department of Pediatrics, Saiseikai Shiga-ken Hospital, Shiga, Japan; and the Department of Pediatrics, Osaka Berland Hospital, Osaka, Japan.
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  • Fumiya Hirayama,

    1. From the Japanese Red Cross Osaka Blood Center, Osaka, Japan; the Department of Pediatrics, Saiseikai Shiga-ken Hospital, Shiga, Japan; and the Department of Pediatrics, Osaka Berland Hospital, Osaka, Japan.
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  • Junji Shimizu,

    1. From the Japanese Red Cross Osaka Blood Center, Osaka, Japan; the Department of Pediatrics, Saiseikai Shiga-ken Hospital, Shiga, Japan; and the Department of Pediatrics, Osaka Berland Hospital, Osaka, Japan.
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  • Shohei Nakauchi,

    1. From the Japanese Red Cross Osaka Blood Center, Osaka, Japan; the Department of Pediatrics, Saiseikai Shiga-ken Hospital, Shiga, Japan; and the Department of Pediatrics, Osaka Berland Hospital, Osaka, Japan.
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  • Keisei Kawa

    1. From the Japanese Red Cross Osaka Blood Center, Osaka, Japan; the Department of Pediatrics, Saiseikai Shiga-ken Hospital, Shiga, Japan; and the Department of Pediatrics, Osaka Berland Hospital, Osaka, Japan.
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Yasuo Fukumori, MS, 3 Blood Examination Sec., Japanese Red Cross Osaka Blood Center, 2-4-43 Morinomiya, Joto-ku, Osaka 536-8505, Japan; e-mail: fukumori@osaka.bc.jrc.or.jp.

Abstract

BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) is a disorder characterized by maternal alloimmunization against paternal fetal platelet antigens. Two healthy, unrelated Japanese women each gave birth to a child with severe NAIT.

STUDY DESIGN AND METHODS: To elucidate the maternal causes of NAIT, we conducted serologic and genetic studies in these two NAIT infants.

RESULTS: The serologic experiments localized the antigens to the glycoprotein (GP) IIIa subunit of the GPIIb/IIIa complex. Sequence-based typing studies subsequently identified a G>A mutation at Nucleotide 1960 (a glutamic acid > lysine substitution at Position 628) in the 11th exon of the GPIIIa gene. This mutation was recently identified in a report as HPA-21bw. Next, it was determined that the cause of NAIT in both cases was the HPA-21bw antigen, as shown by the mothers' antibodies reacting with the mutated GPIIIa-transfected cells, but not with transfectants expressing wild-type GPIIIa. A molecular genetic screening for the HPA-21bw allele among Japanese donors showed that its genetic frequency in the population was 0.53% (10/1888), indicating that HPA-21bw occurs at a low but appreciable frequency in the population. Furthermore, in a retrospective study of 50 previous NAIT cases of unknown causes, we found one NAIT case associated with the HPA-21bw antibody. The two NAIT cases in this study represent the first ones to be associated with HPA-21bw in Japan.

CONCLUSION: We identified the HPA-21bw allele from two unrelated Japanese infants with severe NAIT. We identified 10 individuals (1.06%) positive for the HPA-21bw allele from a genetic screening of 944 Japanese blood donors.

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