Fatal haemolytic transfusion reaction due to anti-Ena and identification of a novel GYPA c.295delG variant in a Thai family

Background and objectives: High-frequency antigen En^a (MNS 28) is expressed on glycophorin A (GPA). En(a-) individuals can form anti-En^a when exposed to GPA. A Thai patient formed an antibody that reacted against all reagent red blood cells (RBCs). The patient received incompatible blood resulting in a fatal haemolytic transfusion reaction (HTR). This study aimed to characterize the antibody detected in the patient and investigate the cause of HTR.

Materials and methods: Blood samples from the patient and three of his family members were investigated. Massively parallel Sequencing (MPS) and DNA-microarray were used for genotyping. Standard haemagglutination techniques were used for phenotyping and antibody investigations.

Results: DNA Sequencing showed the patient was homozygous for GYPA*M c.295delG (p.Val99Ter) predicting En(a-). Three family members were heterozygous for GYPA c.295delG. MPS and DNA-microarray predicted the patient was N- discordant with the N+ RBC phenotype. The patient's plasma was positive with enzyme/chemical-treated reagent RBCs but failed to react with En(a-) and M^k M^k RBCs.

Conclusion: The GYPA c.295delG variant prevented GPA expression on RBCs resulting in En(a-) phenotype. The N+ phenotype result was probably due to the anti-N typing reagent detecting 'N' (MNS30) on GPB. The patient's alloantibody has anti-En^a specificity.

En(a−); Ena (MNS28); MNS blood group system; anti-Ena antibody; haemolytic transfusion reaction.