Care and cure in alloimmunized pregnancies
The presence of red cell alloantibodies in pregnancy can lead to hemolytic disease of the fetus and new born (HDFN), which may result in severe fetal and neonatal anaemia or neonatal hyper bilirubinaemia. If not timely treated, this can cause severe morbidity and even mortality of the child. To identify high-risk alloimmunized pregnant women, the Dutch government (RIVM) organises the Prevention Program Prenatal Screening for Infectious diseases and Erythrocyte Immunisation (PSIE). RIVM provides also anti-D immunoglobulin to RhD-negative women. Already since the ‘60s, the Dept of Immunohematology Diagnostics of Sanquin serves within this government screening program as the national reference laboratory. Sanquin works closely together with the national reference centre for clinical perinatal care to high-risk alloimmunized pregnant women and their children at the Leiden University Medical Center. We also closely work together in diagnostics and treatment of pregnancies complicated by platelet alloantibodies. With our joint efforts, we strive to improve the prevention, the timely diagnosis and treatment of these rare diseases.
Red blood cell and platelet alloimmunisation; diagnostic algorithms to predict clinical relevance
Improving safety of transfusion procedures and blood products is the core of this research line. In immunized patients, transfusion safety depends on alloantibody identification. Alloantibody-mediated transfusion reactions may lead to morbidity and even mortality in critically ill patients. Correct and fast discrimination of pathogenic red blood cell antibodies and platelet antibodies is mandatory. Prevention of alloantibody development will improve transfusion safety in patients who need recurrent transfusions. And will prevent occurrence of haemolytic disease of the fetus and newborn due to transfusion-induced red blood cell antibodies.
Not all red blood cell antibodies will result in transfusion-induced disease. Knowledge on clinically relevance of certain red blood cell alloantibodies is scarce; testing in functional models and collection of clinical data on response to transfusion is necessary. Aim of this research line to design new tools and strategies to provide adequate clinical advice for transfusion support and treatment.
Diagnostic and treatment algorithms in autoimmune blood cell destruction
Primary immune thrombocytopenia (ITP) or autoimmune hemolytic anemia (AIHA) are rare disorders characterized by a variable clinical course and response to therapy. We aim to design a more individualized approach in management of these autoimmune blood disorders. We performed a prospective randomized controlled study testing the hypothesis that early treatment of newly diagnosed ITP with intravenous immunoglobulin (IVIg) would prevent development of chronic disease, the so called “Treatment with or without IVIg in Kids with acute ITP (TIKI)-study” including 200 children. By studying clinical data, genetic data and biomarkers determined in blood samples from these children and from children included in a cohort of children with chronic ITP, we aim to find clues for the pathogenesis of ITP, how to intervene in the clinical course and to predict a clinical relevant bleeding risk in children with newly diagnosed ITP and the response to IVIg treatment. We extend these studies to adult ITP patient samples from other studies (HOVON-64 and STIP study (PI JJ Zwaginga, Sanquin and LUMC). Also in patients with symptomatic autoimmune hemolytic anemia (AIHA) strategies are needed to improve diagnostic and treatment algorithms, including transfusion policy (PI SS Zeerleder, Sanquin and AMC). A nation wide registration study on the relevance of the presence of red blood cell autoantibodies in donors and in patients will start in 2018 (Data Registry in Autoimmune Hemolytic Anemia (DRAIHA study; M. Jalink, MD). A consortium of 15 participating centers has been formed.
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- Evers D, Middelburg RA, de Haas M, Zalpuri S, de Vooght KM, van de Kerkhof D, Visser O, Péquériaux NC, Hudig F, Schonewille H, Zwaginga JJ, van der Bom JG. Red-blood-cell alloimmunisation in relation to antigens' exposure and their immunogenicity: a cohort study. Lancet Haematol. 2016 Jun;3(6):e284-92.
- Thurik FF, Page-Christiaens GC, Ait Soussan A, Ligthart PC, Cheroutre GM, Bossers B, Veldhuisen B, van der Schoot CE, de Haas M. Fetal RHD genotyping after bone marrow transplantation. Transfusion. 2016 Aug;56(8):2122-6.
- Slootweg YM, Koelewijn JM, van Kamp IL, van der Bom JG, Oepkes D, de Haas M. Third trimester screening for alloimmunisation in Rhc-negative pregnant women: evaluation of the Dutch national screening programme. BJOG. 2016 May;123 (6):955-63
- Porcelijn L, Huiskes E, Schipperus M, van der Holt B, de Haas M, Zwaginga JJ; Dutch HOVON 64 Study Group. Lack of detectable platelet autoantibodies is correlated with nonresponsiveness to rituximab treatment in ITP patients. Blood. 2017 Jun 22;129(25):3389-3391.