HPA-5 typing discrepancy reveals an Ile503Leu substitution in platelet GPIa (α2 integrin).

Abstract

BACKGROUND AND OBJECTIVES:

In fetal/neonatal thrombocytopenia, maternal alloimmunization is diagnosed by the identification of the maternal alloantibody and the offending paternal antigen inherited by the foetus/neonate. Today, for practical reasons, most laboratories perform platelet genotyping instead of phenotyping. Here, we report the case of a human platelet antigen (HPA)-5 genotype/phenotype discrepancy observed in a mother who delivered a mildly thrombocytopenic newborn.

MATERIALS AND METHODS:

Platelet antibody detection and platelet phenotyping were performed using the MAIPA assay; platelet genotypes were determined using BeadChip technology (BioArray), PCR-SSP, PCR-RFLP and sequencing.

RESULTS:

Serological investigations revealed the presence of maternal anti-GPIIbIIIa autoantibodies. No alloantibodies were detected. No feto-maternal platelet incompatibility was observed for HPA-1 to -21. The mother and newborn were genotyped as HPA-5aa using BeadChips, but as HPA-5a (weak b) with PCR-SSP and HPA-5ab with PCR-RFLP. Mother's platelets were phenotyped as HPA-5b(+). GPIa exon 13 sequencing confirmed the HPA-5ab genotype of the mother and newborn, and revealed an NM_002203.3:c.1594A>C mutation near the HPA-5 polymorphism (5' side), leading to an I503L amino acid change.

CONCLUSION:

Feto-maternal alloimmunization was ruled out: the neonatal thrombocytopenia probably resulted from maternal anti-GPIIbIIIa autoantibodies. This case highlights that platelet typing should be performed using two different methods to avoid false diagnosis.

• Authors: G Bertrand, V Jallu, T Beranger, F Bianchi, C Casale, V Dufour, C Chenet, J Quesne, C Martageix, C Kaplan
• Journal: Vox sanguinis (Vox Sang) Vol. 105 Issue 1 Pg. 73-6 (Jul 2013) ISSN: 1423-0410 [Electronic] England
• PMID: 23368983 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2013 International Society of Blood Transfusion.

Chemical References

• 5a alloantigen, human
• 5b alloantigen, human
• Antigens, Human Platelet
• Integrin alpha2
• Isoantibodies

Topics

• Adult
• Amino Acid Substitution
• Antigens, Human Platelet (genetics, metabolism)
• Female
• Genotype
• Humans
• Infant, Newborn
• Integrin alpha2 (genetics)
• Isoantibodies (blood)
• Male
• Mutation, Missense
• Polymorphism, Restriction Fragment Length
• Thrombocytopenia, Neonatal Alloimmune (blood, genetics)