Severe fetomaternal alloimmune thrombocytopenia due to anti-human platelet antigen (HPA)-1a in a mother with a rare and silenced ITGB3*0101 (GPIIIa) allele.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Smith
G A
GA
Platelet Immunology Reference Laboratory, National Health Service Blood and Transplant, Cambridge, UK.
Rankin
A
A
Riddle
C
C
Cheetham-Wilkinson
C
C
Ranasinghe
E
E
Ouwehand
W H
WH
Watkins
N A
NA
D000328:Adult; D016824:Antigens, Human Platelet / Q000276:immunology*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D039661:Integrin beta3; D007518:Isoantibodies / Q000032:analysis / Q000276:immunology; D010641:Phenotype; D017713:Platelet Transfusion; D011247:Pregnancy; D054098:Thrombocytopenia, Neonatal Alloimmune / Q000175:diagnosis* / Q000276:immunology* / Q000628:therapy
D016824:Antigens, Human Platelet; C061248:ITGB3 protein, human; D039661:Integrin beta3; D007518:Isoantibodies; C083451:human platelet antigen 1b