The risk of severe neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies is correlated to maternalABOtypes, and this study indicates that the observation is due to genetic properties on the maternal side. == 1. human platelet antigen (HPA)-1 alloantigen system is the most common underlying cause of neonatal alloimmune thrombocytopenia (NAIT), a condition where maternal alloantibodies opsonize foetal platelets during pregnancy and reduce their survival in circulation. The incompatibility is based on a single-nucleotide polymorphism (SNP) which results in a leucine/proline substitution at residue Otamixaban (FXV 673) 33 in the3 integrin that constitutes membrane glycoprotein3 [GPIIIa] present on platelets in complex withIIb integrin [GPIIb] [1]. On platelets, theIIb3 [GPIIb/IIIa] is also the major carrier of blood group A antigen [2]. About 10% of HPA-1a negative women who have been pregnant with an HPA-1-incompatible child have detectable HPA-1a antibodies [3]. In several studies, a correlation between maternal antibody level and the severity of thrombocytopenia Otamixaban (FXV 673) in the newborn has been shown [46]. The alloimmunization is strongly associated with theHLA-DRB3*01 : 01allele [3,7,8]; however, only about 30% of the women with this HLA antigen are immunized. Except for the incompatibility in platelet antigen and the association to HLA, other factors which may influence the immune response to HPA-1a have not been identified. In the present study, we have examined the maternal ABO blood groups and frequency of HPA-1a-immunization of the women identified in the large prospective screening and intervention study carried out in Norway from 1995 to 2004. We included 152 HPA-1a-immunized women, 146 of whom had altogether 158 HPA-1-incompatible pregnancies in the screening study. The ABO distribution among immunized women was investigated, and the maternal ABO phenotype andABOgenotype was correlated to the severity of thrombocytopenia of the newborn. == 2. Materials and Methods == == 2.1. Patients == Otamixaban (FXV 673) Pregnant women were recruited for HPA-1 allotyping from three regions in Norway between December, 1995 and March, 2004 [3]. Samples for routine Rh(D) typing were also used for determining HPA-1 allotype by flow cytometry (anti-CD61 mAb), enzyme-linked immunosorbent assay (ELISA), or polymerase chain reaction (PCR) as previously described [9]. A total of 100,448 pregnant women were typed for the platelet antigen HPA-1a, and 2,111 of those were HPA-1a negative (2.1%). Of these, 1,990 were further tested, and anti-HPA-1a antibodies were detected in 154 women during the pregnancy. In total, 146 of these immunized women underwent 158 HPA-1a-incompatible pregnancies. ABO blood group typing was performed by conventional technique. Genomic typing of HPA-1 (ITGB3;rs5918 in dbSNP) andABOin the neonates was performed in samples from cord blood or buccal swabs. For the newborns, theABOgenotype was used to predict the ABO blood group. In this context, we have defined ABO incompatibility only as an A1phenotype in the newborn, in blood group O mothers, because individuals with A2, and the majority of individuals with B phenotype, express only low levels of corresponding antigens on the surface of platelets [2,1012]. Thrombocytopenia was defined as a platelet count 150 109/L, and severe thrombocytopenia less than 50 109/L measured in cord blood and/or capillary blood at birth. Detection of anti-HPA-1a IgG antibodies was performed by stream cytometry and quantified with monoclonal antibody immobilization of platelet antigen assay (MAIPA) [3], utilizing the anti-CD61 monoclonal antibody clone Y2/51 (Dako, Glostrup, Denmark) for immobilisation of platelet glycoproteins. Females were examined at several period points through the being pregnant, and those using a positive antibody check anytime during the being pregnant had been characterized as immunized. Nineteen females were principal immunized through the examined being pregnant, 13 of the were primigravida. Others might have been immunized regarding the a prior being pregnant. Prior affected pregnancies weren’t excluded being a cause of serious NAIT. The NAIT medical diagnosis was predicated on maternal anti-HPA-1a antibodies and HPA-1a antigen incompatibility. Various other possible known reasons for thrombocytopenia (an infection, maternal ITP, etc.) weren’t signed up. Informed CD118 consent was supplied relative to the declaration of Helsinki. The analysis was accepted by the Regional Committee for Medical Analysis Ethics, North Norway (acceptance no..