Challenging the dogma: Red blood cell-directed autoimmunity as risk factor for red blood cell alloimmunisation after blood transfusion

Red blood cell autoimmunity and alloimmunity are potentially linked. Quantification of this association can tailor extensively matched red blood cell transfusions in patients with autoimmunity. Using an incident new-user cohort comprising 47 285 previously non-transfused, non-alloimmunised patients, we compared transfusion-induced red blood cell alloimmunisation incidences in direct antiglobulin test (DAT)-positive and control patients. Additionally, we performed case-control analyses to handle potential confounding by clinical immunomodulators. Among (IgG and/or C3d) DAT-positive patients (N = 380), cumulative red blood cell alloimmunisation incidences after 10 units transfused reached 4.5% (95% confidence interval [CI] 2.5-8.2) versus 4.2% (CI 3.9-4.5, p = 0.88) in controls. In case-control analyses, alloimmunisation relative risks among DAT-positive patients increased to 1.7 (CI 1.1-2.8). Additional adjustments for pre-DAT transfusion exposure or the extent of Rh/K mismatching did not impact results. In conclusion, while patients with DAT positivity show an intrinsically increased alloimmune red blood cell response, their absolute risk is comparable to control patients due to counteracting co-existing immunosuppressive conditions. Consequently, isolated DAT positivity in patients lacking overt haemolysis or complicated alloantibody testing does not seem to warrant extended matching strategies.