Towards routine HPA-screening in pregnancy to prevent FNAIT: Assessing disease burden, optimizing risk group selection and safety of IVIg treatment. (LSBR 1440)
Project leader: Prof. dr. Dick Oepkes, Dept. of Obstetrics, LUMC, Prof. Dr. C. Ellen van der Schoot (co-applicant), Dept. of Experimental Immunohematology, Sanquin and Prof. Dr. Masja de Haas (co-applicant), Dept. of Translational Immunohematology, Sanquin and Dept. of Immunohematology and Blood Bank, LUMC
Ph.D. student: Dian Winkelhorst, MD (July 2015 – July 2017 (89%); Jan 2017 – April 2019 (100%))
Research technician: Ugne Kazlauskaite, BSc (18 months, Sanquin)
Physiologist: Janine van Klink, MSc, PhD (89%, 7 months, LUMC)
Gynaecologist: Marijke Kamphuis, MD, PhD (3 months, LUMC)
Ph.D. student: Thijs de Vos, MD (Oct 2018 – Sept 2019, Sanquin)
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the most common cause of thrombocytopenia in otherwise healthy newborns. During pregnancy, maternal immunization against unknown, paternally derived, antigens on fetal blood cells can occur.
Alloantibodies against HPA-1a are the most commonly involved in (severe cases of) FNAIT. Clinical presentation can vary from an asymptomatic thrombocytopenia or relatively harmless bruises and petechiae to severe life-threatening and invalidating intracranial hemorrhages (ICHs). Once alloimmunization is detected and diagnosed, subsequent pregnancies can be treated to prevent the recurrence of bleeding complications. Unfortunately, in absence of population-based screening, alloimmunization is virtually only known after an affected fetus or newborn.
Affected infants that might have been prevented if only the alloimmunization was known and treated prior to the occurrence of bleeding complications. Implementation of population-based screening, in order to prevent FNAIT, can help identifying of alloimmunization prior to bleeding. To guide careful consideration of screening, Wilson and Jungner (W&J) proposed and published ten screening criteria that were adopted by the World Health Organization (WHO).
We designed and started a nationwide, prospective observational study to obtain incidence numbers and missing knowledge on natural history; the HIP-study (HPA-screening In Pregnancy). First, we have designed and validated an assay for high-throughput screening and detection of HPA-1a pregnant women, that are at risk for alloimmunization. Further, with the collection of an unique control group of immunized pregnancies without clinical disease we will be able to adequately assess factors that enable a risk assessment and predict which fetuses are at high risk for developing bleeding complications. The HIP study will close in March 2020.
Collection and analysis of data will be completed early in 2021. It is expected, the HIP study will deliver the missing knowledge to consider the start of a screening program for HPA-1a alloimmunisation in pregnancy.