Associations between blood donors, component modifications, and the alloimmunization of transfusion recipients

Prior studies have evaluated transfusion recipient variables impacting red blood cell (RBC) alloimmunization, but few focused on potentially modifiable blood donor or blood component variables.

Data from the Recipient Epidemiology and Donor Evaluation Study (REDS)-III, which links donor, component, and patient data in an integrated database, were accessed. For any given RBC unit with sufficient blood donor and component data, we determined if the transfusion recipient experienced a new RBC alloimmunization event ("case") within 16 weeks of the transfusion or not ("control"). Recipient diagnoses were included in the case-control matching algorithm.

A total of 2676 cases were matched with 10,160 controls. In a multivariate conditional logistic regression analysis, recipients who received an RBC unit from donors with a different ABO group had a higher risk of alloimmunization (OR 1.60, 95% CI: 1.35-1.89, p < .001). Likewise, recipients who received RBCs from older donors had a higher risk of RBC alloimmunization (OR 1.01 per year of age, 95% CI: 1.00-1.01, p < .001). Irradiated RBCs were associated with a decreased risk of RBC alloimmunization in transfusion recipients (OR 0.52, 95% CI: 0.46-0.59, p < .001), though a sub-analysis of RBCs transfused to people with sickle cell disease showed no such association (p = .75). Recipients who received RBCs stored for a longer duration also had a lower risk (OR 0.99 per day of storage, 95% CI: 0.99-0.99, p < .001) of alloimmunization.

This case-control study identified donor and component variables associated with recipient RBC alloantibody formation. Future mechanistic studies exploring these associations are warranted.