Thesis Jorn Gerritsma

Summary

Sickle cell disease (SCD) is the most common recessive monogenetic disorder worldwide. It is a severe hemoglobinopathy that leads to anemia, painful vaso-occlusive crises and is associated with a reduced life expectancy. Red blood cell (RBC) transfusions are an important treatment modality, however this therapy is not without risk. Therefore, this thesis focussed on improving safety and effectiveness of RBC transfusions for this vulnerable population.

The first part of the thesis studies the genetic risk factors for alloimmunization in SCD patients. We demonstrate an association of specific genetic polymorphisms with an increased risk of RBC antibody formation.

The second part of this thesis studies the RBC survival kinetics and clinical complications of RBC transfusion in SCD. We demonstrate, by transfusion of biotin labeled RBCs in chronically transfused SCD and β-thalassemia patients, that the survival kinetics of transfused RBCs seems to be different compared to healthy volunteers. Importantly, patients chracteristics appear to be the most important factor to determine RBC survival. Moreover, we show that these RBC transfusions do not elicit an innate immune response, despite an exhausted hemoglobin scavenging system in the patients. Still, RBC transfusions in SCD are associated with severe hemolytic transfusion reactions. In the final chapter of this thesis we demonstrate that, even with the use of extended matching protocols, hemolytic transfusion reactions remain relatively common, and diagnosis of this complication remains a challenge.