BACKGROUND AND OBJECTIVES: Fetomaternal alloimmune thrombocytopenia (FMAIT) is caused by maternal antibodies against a human platelet antigen (HPA) present on fetal, but absent from maternal platelets. We identified and characterized a case of FMAIT due to anti-HPA-1a in a mother with an HPA-1a1b genotype. MATERIALS AND METHODS: The first child of a 29-year-old mother presented with a petechial rash and a platelet count of 8 x 10(9) per l. Upon routine serological investigation, a discrepancy between the HPA-1a genotype and phenotype prompted the sequencing of the 15 exons of the ITGB3 (integrin beta3, GPIIIa and CD61) gene in the mother. RESULTS: The mother was genotypically HPA-1a1b heterozygous but phenotyped as HPA-1a negative. Sequencing of the ITGB3 exons confirmed HPA-1a1b heterozygosity, but also identified a novel single nucleotide insertion in exon 10 leading to a frameshift and premature termination at amino acid 471 of ITGB3. Maternal anti-HPA-1a was detected but with a pattern typical for a low-affinity antibody. Three transfusions of HPA-1a and -5b negative neonatal platelet concentrates were required to return to a safe platelet count. CONCLUSION: A rare ITGB3 allele was uncovered by the investigation of a severe case of alloimmune thrombocytopenia in a mother with HPA-1a antibodies who genotyped as HPA-1a1b.
BACKGROUND AND OBJECTIVES:Fetomaternal alloimmune thrombocytopenia (FMAIT) is caused by maternal antibodies against a human platelet antigen (HPA) present on fetal, but absent from maternal platelets. We identified and characterized a case of FMAIT due to anti-HPA-1a in a mother with an HPA-1a1b genotype. MATERIALS AND METHODS: The first child of a 29-year-old mother presented with a petechial rash and a platelet count of 8 x 10(9) per l. Upon routine serological investigation, a discrepancy between the HPA-1a genotype and phenotype prompted the sequencing of the 15 exons of the ITGB3 (integrin beta3, GPIIIa and CD61) gene in the mother. RESULTS: The mother was genotypically HPA-1a1b heterozygous but phenotyped as HPA-1a negative. Sequencing of the ITGB3 exons confirmed HPA-1a1b heterozygosity, but also identified a novel single nucleotide insertion in exon 10 leading to a frameshift and premature termination at amino acid 471 of ITGB3. Maternal anti-HPA-1a was detected but with a pattern typical for a low-affinity antibody. Three transfusions of HPA-1a and -5b negative neonatal platelet concentrates were required to return to a safe platelet count. CONCLUSION: A rare ITGB3 allele was uncovered by the investigation of a severe case of alloimmune thrombocytopenia in a mother with HPA-1a antibodies who genotyped as HPA-1a1b.