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


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.


CONCLUSIONS
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.
Platelet Immunology Unit, INTS, Paris, France. gbertrand@ints.fr
G
G
Bertrand
V
V
Jallu
T
T
Beranger
F
F
Bianchi
C
C
Casale
V
V
Dufour
C
C
Chenet
J
J
Quesne
C
C
Martageix
C
C
Kaplan
D000328:Adult; D019943:Amino Acid Substitution; D016824:Antigens, Human Platelet / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D039421:Integrin alpha2 / Q000235:genetics*; D007518:Isoantibodies / Q000097:blood; D008297:Male; D020125:Mutation, Missense; D012150:Polymorphism, Restriction Fragment Length; D054098:Thrombocytopenia, Neonatal Alloimmune / Q000097:blood / Q000235:genetics
C071092:5a alloantigen, human; C055973:5b alloantigen, human; D016824:Antigens, Human Platelet; D039421:Integrin alpha2; D007518:Isoantibodies