Fetal-neonatal alloimmune thrombocytopenia and unexpected Glanzmann thrombasthenia carrier: report of two cases.
BACKGROUND
Discrepancy between phenotyping and genotyping during the investigation of maternofetal alloimmunization leads to the identification of defects on genes encoding membrane glycoproteins (GPs) IIb and IIIa.


METHODS
Human platelet (PLT) alloantigen (HPA)-1 and -3 PLT phenotypes and genotypes were performed by use of, respectively, the monoclonal antibody-specific immobilization of PLT antigens and the polymerase chain reaction (PCR)-sequence-specific priming techniques for up to 2400 families with thrombocytopenic newborn. When a discrepancy was detected, genomic DNA from the mother was amplified for coding sequences of either the GPIIb or GPIIIa genes. The genetic abnormality responsible for the discrepancy was determined by direct sequencing of the PCR products.


RESULTS
Two cases of discrepancy were identified among 2400 families tested. In the first case, Mother L, serologically assigned as HPA-1b-homozygous, was genotyped HPA-1a/1b. In the second case, Mother S, serogically defined HPA-3b-homozygous, was genotyped HPA-3a/3b. DNA sequence analysis revealed for Mother L a T(1447)-->C a point mutation within exon 10 of the GPIIIa gene and for Mother S a C(480)-->G point mutation within exon 4 of the GPIIb gene. These mutations reported in Glanzmann thrombasthenia (GT) patients account for nonexpression of the implicated allele on the PLT surface. Thus, the mothers are GT carriers. Alloantibodies, hallmarks of immunization, were not detected in the maternal serum samples.


CONCLUSIONS
Although this situation is rarely encountered, it is important to combine phenotyping and genotyping to avoid false PLT typing assignation and erroneous diagnosis when alloimmunization might occur.
Jallu
Vincent
V
INTS, Platelet Immunology Laboratory, Paris, France.
Bianchi
Frédéric
F
Kaplan
Cécile
C
D016824:Antigens, Human Platelet / Q000235:genetics / Q000276:immunology; D003951:Diagnostic Errors; D004899:Erythroblastosis, Fetal / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D010641:Phenotype; D017354:Point Mutation; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000175:diagnosis / Q000276:immunology; D013915:Thrombasthenia / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D013921:Thrombocytopenia / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*
D016824:Antigens, Human Platelet