Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the most common cause of thrombocytopenia in otherwise healthy newborns. During pregnancy, fetal blood cells enter the maternal circulation... Show moreFetal and neonatal alloimmune thrombocytopenia (FNAIT) is the most common cause of thrombocytopenia in otherwise healthy newborns. During pregnancy, fetal blood cells enter the maternal circulation and might result in alloimmunization, the maternal production of antigen-specific alloantibodies. Once these alloantibodies enter the fetal circulation, they can cause damage. 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 needs to be a carefully weighed decision. The benefits of screening need to outweigh the potential harm. To guide careful consideration and decision-making, Wilson and Jungner (W&J) proposed and published ten screening criteria. With this thesis, important evidence is presented that can be used for the fulfillment of the W&J criteria. Show less
Ree, I.M.C.; Smits-Wintjens, V.E.H.J.; Bom, J.G. van der; Klink, J.M.M. van; Oepkes, D.; Lopriore, E. 2017
Transfusion of red blood cells (RBCs) causes exposure to foreign antigens and, consequently, may induce alloimmunization. This research focused on identifying clinical determinants of RBC... Show moreTransfusion of red blood cells (RBCs) causes exposure to foreign antigens and, consequently, may induce alloimmunization. This research focused on identifying clinical determinants of RBC alloimmunization, eventually aiming to prevent alloimmunization by pre-emptively select extended matched blood for the predicted responder patient. Both RBC antigen intrinsic characteristics and patient-related factors were studied. Regarding antigen immunogenicity, K was confirmed to be the most potent antigen, followed by E, Cw, e, Jka and c. Of importance, anti-Jka is known to easily induce complement-mediated hemolysis. Inflammation due to severe bacterial and viral infections was associated to increased RBC alloimmunization incidences. Remarkably, although in line with murine models, Gram-negative bacteremia coincided with a twofold reduction of alloimmunization risk. In a non-hemoglobinopathy population, alloimmunization post-splenectomy was a highly unlikely event. Consequently, the Caucasian splenectomized patient does not benefit from RBC products matched beyond ABO/RhD. Patients with acute (either myeloid of lymphoblastic) leukemia, mature lymphomas, myelodysplastic syndrome, or patients post-autologous or -allogeneic stem cell transplantation demonstrated strongly reduced incidences of RBC alloimmunization, primarily explained by the intense immunosuppressive nature of treatments. Consequently, matching for the MDS population deserves renewed focus and should be based on the cumulative transfusion burden rather than on the diagnosis itself. Show less
Fetal anemia is a serious complication in pregnancy, and is associated with perinatal mortality and morbidity. One of the major advances in the management of fetal anemia was the introduction of... Show moreFetal anemia is a serious complication in pregnancy, and is associated with perinatal mortality and morbidity. One of the major advances in the management of fetal anemia was the introduction of the intrauterine blood transfusion (IUT). This thesis presents several studies on IUT for fetal anemia. We described current indications and complications of IUT, we analyzed contributing factors for adverse perinatal outcome and we showed learning curves of for this procedure. Furthermore, we report the long-term outcome after IUT in a large cohort of children (the LOTUS study). The vast majority (over 95%) of children treated with IUT for severe alloimmune anemia have a normal neurodevelopmental outcome, confirming the success of this antenatal treatment. From the studies described in this thesis, we conclude that after more than 20 years of improved knowledge and skills, IUT is to be considered a safe and successful method to treat severe fetal anemia for different causes. Show less
Lindenburg, I.T.M.; Kamp, I.L. van; Oepkes, D. 2014
The scope of the work described in this thesis is to examine whether potential transfusion related and clinical risk factors modulate the risk of alloimmunization in a general, previously not... Show moreThe scope of the work described in this thesis is to examine whether potential transfusion related and clinical risk factors modulate the risk of alloimmunization in a general, previously not transfused, non alloimmunized population of transfusion recipients. In these studies we emphasize the methodological aspects of observational research in clinical transfusion medicine Show less
This thesis focuses on several aspects related to the hematological outcome of infants with hemolytic disease of the fetus and newborn (HDFN) due to red blood cell alloimmunization, including... Show moreThis thesis focuses on several aspects related to the hematological outcome of infants with hemolytic disease of the fetus and newborn (HDFN) due to red blood cell alloimmunization, including pathogenesis and management of the disease. The presence of leukocytopenie and thrombocytopenia support the mechanism of suppression of thrombopoiesis and granulopoiesis in favor of the increased erythropoiesis stimulated by anemia and hypoxia. In addition to the problems caused by a shortage of platelets and white and red blood cells, the excess of the red blood cell metabolites bilirubin and iron also contribute to the morbidity of the disease. This thesis also contains a systematic review that demonstrates that there is lack of high level evidence promoting the use of intravenous immunoglobulin (IVIg) to prevent exchange transfusions in HDFN. Irrespective of the controversy concerning the use of IVIg, this thesis shows that intensive follow-up is indicated in both Rhesus D and non-Rhesus D HDFN and raised awareness about the associated morbidity is of paramount importance. Finally, this thesis also contains future research questions concerning HDFN. Show less
