Search

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by maternal antibodies that cross the placenta in connection with pregnancy and destroy fetal platelets. Recently, maternal T cell responses associated with FNAIT have been studied at the clonal level. These T cell clones recognize an integrin β3 epitope, which is anchored to the HLA-DRB3∗0101-encoded MHC molecule DR52a. The same MHC allele is strongly associated with FNAIT. As the production of pathological antibodies reactive with fetal platelets is likely dependent on these T cell responses, there exists a potential for preventing FNAIT by targeting these T cells., (Copyright © 2011. Published by Elsevier Ltd.)

The issue of whether or not antibody quantity during pregnancy is related to severity of neonatal alloimmune thrombocytopenia remains unresolved. In this article we cite studies in support of both sides of the argument and highlight some of the reasons that may lie behind the observed differences amongst those studies. It may well be that some of the reasons for the discrepant results could be due to the type of study carried out (eg retrospective versus prospective), the sample size, the timing of antibody sampling, and possibly the type or protocol of assay used. Another major reason is the absence, until recently, of an international anti-HPA-1a standard.

Background: Around 80% of severe neonatal alloimmune thrombocytopenia (NAIT) cases in the Caucasian population are due to anti-HPA-1a antibodies. However, the relationship between anti-HPA-1a antibody quantity and severity of NAIT has been subject to debate, possibly due to discrepant results between studies incorporating different assays (such as ELISA and MAIPA) and the number of samples. The aim of this study was to compare the level of maternal anti-HPA-1a antibodies in the same samples, using two different methods; quantitative ELISA and quantitative MAIPA. At the same time, the relationship between the maternal anti-HPA-1a antibody quantity and the newborn platelet count was examined., Materials and Methods: Plasma samples were obtained from HPA-1a negative mothers giving birth to children with different platelet counts (i.e. NAIT vs normal platelet count). The antibody levels were quantified blindly in the respective assays using standards calibrated against the international standard NIBSC 03/152., Results: A linear correlation was observed between quantitative MAIPA and quantitative ELISA results. However, there were many individual variations giving a mean ratio of disagreement between the quantitative ELISA and quantitative MAIPA of 2.84. Furthermore, regression analysis revealed a significant relation between anti-HPA-1a antibody quantity measured by MAIPA, but not ELISA, and the newborn platelet count., Conclusion: The results indicate that differences observed between various studies with regard to NAIT severity and anti-HPA-1a quantity could partly be due to different assays used.

This brief report summarizes the use of surface plasmon resonance technology (SPRT) in probing HPA-1a antigen-antibody interactions, based on a poster presented at the 60th meeting of the American Association of Blood Banks. It was concluded that the GP purification method could affect the performance of antigen in SPRT. It also highlighted that chips immobilised with Monoclonal antibody (Mab)-purified GP-IIb/IIIa work satisfactorily with both monoclonal and recombinant Abs with the appropriate concentration and binding affinity, while determination of the avidity and concentration of maternal polyclonal antibodies in respect to clinical severity on NAIT warrants further development.

Thrombocytopenia is the second commonest haematological abnormality in the neonatal period after anaemia due to iatrogenic blood letting. One to four percent of all newborn babies have a platelet count < 150 x 10(9)/l at birth and approximately 20-40% of neonates in intensive care units are affected by neonatal thrombocytopenia. The most common cause of severe neonatal thrombocytopenia is fetomaternal platelet incompatibility and subsequent alloimmunisation. During the last decade recent advances in molecular techniques have led to rapid and efficient methods for diagnosis. Progress in fetal medicine has enabled accurate determination of fetal status, allowing improvements in fetal diagnosis and therapy. Human platelet antigen (HPA)-1a is by far the most frequently involved platelet antigen system in Caucasians accounting for 90% of cases, followed at a much lower frequency by HPA-5b (5-15%) and HPA-3a. The incidence is estimated to be 1 per 2000 to 1 per 5000 live births, but this is low in comparison to the incidence of fetomaternal platelet antigen incompatibility especially for the HPA-1 alloantigen system in the Caucasian population in whom the estimated frequency of HPA-1b1b individuals is 2%. Retrospective and prospective studies have reported that the immunogenetic background is important, and the chance of HPA-1a alloimmunisation is strongly associated with maternal HLA class II DRB3*0101 (DR52a) type. A significant association (p = 0.004) between severe thrombocytopenia and a third trimester antiHPA titre >1:32 has been observed. It is now possible to genotype the fetus or neonate and the parents, which provides confirmation as to which HPA systems are incompatible between the mother and father. Simultaneous genotyping of HPA-1, 2, 3 and 5 can be carried out using the polymerase chain reaction-sequence specific primers (PCR-SSP) protocol, which has been widely used for HLA class II determination. The platelet count may continue to fall during the first 48 h after birth and the risk of intracranial bleeding is highest during this period. The best option is transfusion of specially selected antigen negative compatible donor platelets or if unavailable, maternal washed platelets. Antenatal screening for the most common form of fetomaternal alloimmune thrombocytopenia (FMAIT), due to antiHPA-1a is under consideration, but there is no established method at present. The Scottish National Blood Transfusion Service started a study in August 1999 on 25,000 pregnancies to carry out a cost benefit analysis of routine antenatal screening. The aims of the study are to determine the frequency of HPA-1b homozygosity; monitor antibody titres during pregnancy and confirm correlation of antibody emergence with HLA-DRB3*0101, and finally to access cost effectiveness of routine screening across Scotland. Of 26,509 women screened in three Scottish regions 501 (1.9%) are HPA-1b homozygous and about 9%, of the consented women are antibody positive.