Anti-HPA-9bw (Maxa+) Feto-Maternal Alloimmunization and Clinically Severe Neonatal Thrombocytopenia: Difficulties in Diagnosis and Therapy, Report on 12 Cases.

Since the first documented case of neonatal thrombocytopenia (NAIT) due to anti HPA-9bw (Maxa+)1, no clinical data report has appeared in the literature. We have conducted a retrospective analysis of the cases referred to the INTS (Paris) in the recent years. This analysis confirms that anti HPA-9bw (Maxa+) NAIT is a clinically severe syndrome which requires prompt diagnosis, in spite of difficulties, and maternal platelet transfusion therapy. This report concerns 8 families (12 neonates) investigated for neonatal thrombocytopenia (initial case included). The diagnosis was performed by genotyping and identification of the maternal alloantibody. The maternal sera reacted with paternal platelets in the MAIPA technique with anti GPIIb-IIIa monoclonal antibodies. No reaction was observed with a standard panel of typed donors and with their own platelets. In 2 families the diagnosis was ascertained retrospectively and the maternal alloantibody not detectable few months after delivery. Platelet genotyping did not show incompatibilities for the known platelet specific alloantigen systems HPA-1 to 11 and HPA-15 when tested in 7 out of 8 families. In the last one, incompatibility was found for HPA-3 without anti HPA-3b maternal alloantibody. As the father was HPA-9bw heterozygous in all the cases, the infant or fetus was genotyped to ascertain the diagnosis. In 10/12 cases, the infant was incompatible with the mother and therefore the diagnosis was straightforward. Four index cases were first-born children. Hemorrhage was present in 5/9 neonates, all but two infants had severe thrombocytopenia at birth, platelet counts<20.109/l and intracranial hemorrhage was documented in 1 patient, otherwise sonograms were normal. When bleeding was present maternal platelet transfusion therapy was given, most of the time because of poor response to random platelet transfusion. In 3 families successive pregnancies were followed up. In one case the fetus was compatible , in another case the 2nd child was moderately affected and in the last case maternal antenatal therapy (IvIgG) was given for fetal thrombocytopenia. Since 1999 we screen for the potential implication of rare antigens in suspected cases of NAIT when there is no other incompatibility. This screening has led us to characterize a new platelet antigen2. Anti HPA-9bw NAIT accounts for ~2% of our confirmed NAIT cases (parental antigen incompatibilities and presence of maternal alloantibodies). Difficulties in laboratory diagnosis for HPA-9bw NAIT mainly relies on the identification of the alloantibody and the paternal heterozygous status for the antigen. We have observed that monoclonal antibodies could interfere with the alloantibody binding in the MAIPA technique leading to false negative results. The diagnosis could only be confirmed after infant genotyping, in our series we have found 1 neonate and 1 fetus compatible with their mother excluding this antigen to be implicated in fetal/neonatal thrombocytopenia. In conclusion, laboratory investigation of a suspected NAIT case should be carried out in a well-versed laboratory for optimal testing. Therapy requires a strict collaboration between clinicians and blood bank services. Appropriate management and antenatal therapy should be considered for successive pregnancies to prevent fetal bleeding.