Description
Fetal neonatal alloimmune thrombocytopenia (FNAIT) which may result in intracranial haemorrhage, fetal death or lifelong disability is highly underdiagnosed, inadequately prevented and managed. The project objective is to implement low-cost methods of identifying women at risk of FNAIT, to analyze the biomarkers of FNAIT development and to establish a biobank. We plan to standardize methods for prevention and follow up for pregnant women at risk. The outputs of the project will be protocols of state-of-the-art procedures for investigation of pregnant women, the biobank of samples and publications related to the FNAIT. The beneficiaries of the Project are pregnant women, their fetuses and new-borns. The Polish and Norwegian research teams are highly complementary and will both benefit from the collaboration by sharing their expertise. The project will be the basis for longstanding collaboration aimed at detection and prevention of FNAIT through improvement of pregnancy control programs, introduction of prophylaxis (collaboration with Prophylix Pharma AS, www.prophylixpharma.com). The biobank will be used in future research.
Summary of project results
Fetal / neonatal alloimmune thrombocytopenia (FNAITP) is a dangerous though rare disease (1/1000 pregnancies) that occurs in women with no HPA-1a antigen when they produce antibodies to this antigen. As result, fetal platelets are destroyed which induces dangerous bleedings. The most severe is intracranial hemorrhage (ICH) that can cause fetal / infant death. Such dramatic effects can be prevented by FNAIT treatment during pregnancy provided women/pregnancies with antibodies are identified as soon as possible. Up to date there were no such routine programs either in Poland or elsewhere. In our project we developed methods of negative HPA-1a women identification and we performed the diagnostics which allow to refer women at risk to a gynecologist who specializes in prenatal treatment. In the overall number of 24 267 tested women we identified 607 HPA-1a negative ones 69 of whom had antibodies and were directed to a reference center. We developed and implemented a test for antibody concentration which is helpful in making decisions on treatment. We also developed a modern noninvasive genetic test for identification of HPA-1a negative fetuses which do not require treatment since antibodies pose no threat. According to literature the risk of severe thrombocytopenia in HPA-1bb women with antibodies is estimated at 30%. In our study group successful prenatal treatment was introduced in all but one case (it had low antibody concentration). This newborn was treated just after delivery and is now healthy. The short term impact of the project was examination of pregnancies in 607 HPA1a negative Polish women at risk of FNAIT and successful treatment of cases with antibodies; these are direct beneficiaries of the program. The long-term impact of the project is development of a system of screening and diagnostics to be offered to gynecologists and pregnant Polish women for routine use. It is ready to be used for identification of women in need of immunoprophylaxis (currently under development by Norwegian Company Prophylix Pharma AS). The above achievements highly promote obligatory HPA-1 typing and improve diagnostics and treatment of FNAIT in Poland. An important outcome of the project is formation of a unique biobank with time-course samples and clinical information on large group of HPA-1bb women. These valuable samples will be used for further long-term cooperation between Polish and Norwegian Partners.
Summary of bilateral results
The UiT and IHTM partnership developed during project add important scientific value to it. The Polish party contributed by performing the recruitment, screening and follow up of all women included in the study as well as by implementation of several diagnostic tests to identify the cases at risk and in need of treatment. The screening was performed according to the method developed by the Norwegian Partner which was improved by Polish partner by introduction of DNA analysis and authomatisation . The workshops and discussions during the project-study established a valuable system of diagnostics to be continued in routine use in IHTM laboratory. A particularly significant outcome of the Polish Norwegian cooperation is the biobank of samples for the future study of FNAIT pathogenesis. Currently one such project is financed. Both Partners have applied for additional funds. There is also cooperation based on the clinical and laboratory data with the purpose of analyzing some aspects of FNAIT pathogenesis. This activity will be continued. Congress presentations, review manuscripts and original papers based on the clinical data and biobank samples collected by the Polish Partner will be shared by the Norwegian and Polish scientists/researchers/doctors. The Norwegian party will perform expertise statistical analysis of data and make available its modern laboratory setting to facilitate extensive and up-dated research on FNAIT pathomechanisms and potential methods of prevention. Bilateral funding contributes to the strengthening of our relations. In 2017 we plan to jointly apply for at least two further projects.