Thesis defense Dorothea Evers

Clinical Determinants of red cell alloimmunization: implications for preventative antigen matching strategies

On 19 December 2017 (13.45 hrs) Dorothea Evers defended her thesis 'Clinical Determinants of red cell alloimmunization: implications for preventative antigen matching strategies' at Leiden University

She received her doctorate cum laude.


Promotores: prof JG van der Bom MD PhD and prof JJ Zwaginga MD PhD
Copromotor: R.A. Middelburg PhD

Venue: Academiegebouw, Leiden University



Transfusion of red blood cells causes exposure to non-self antigens. Consequently, RBC transfusions may induce alloantibody formation and its, sometimes detrimental, hemolytic complications.
The studies described in this thesis have focused on identifying clinical determinants of RBC alloimmunization, eventually aiming to offer extended matched blood to only the predicted high-risk responder patients.
Alloimmunization depends on both antigen prevalences as well as antigen immunogenicity. This thesis demonstrates that K is the most potent antigen, followed by E, Cw, e, Jka and c. Especially the results regarding anti-Jka are of importance, as prevention is currently not routinely aimed for in developed countries and as it easily induces complement mediated hemolysis.
Several clinical conditions modulate an immune response after RBC transfusion. Inflammation in the setting of severe bacterial and viral infections were demonstrated to be associated to increased RBC alloimmunization incidences. Remarkably, although in line with murine models, Gram-negative bacteremia coincided with an almost twofold reduction of alloimmunization risk.
In a non-hemoglobinopathy population, alloimmunization following surgical splenectomy was a highly unlikely event. Consequently, the Caucasian, post-splenectomy patient does not benefit from RBC products matched beyond ABO/RhD.
Patients with acute leukemia (either of myeloid or lymphoblastic origin), with mature (B or T cell) lymphomas, or patients post-autologous or -allogeneic stem cell transplantation, demonstrated strongly reduced incidences of RBC alloimmunization, which were primarily explained by the strongly immunosuppressive nature of treatments. Alloimmunization risks of non-treated patients with these diseases were similar to risks in the general transfused population. Consequently, current matching for the MDS population deserve renewed focus: the decision to transfuse extended donor-matched products should not be based on the diagnosis itself, but on factors associated to an increased cumulative alloimmune response e.g. a high transfusion burden.