Red blood cell alloantibodies are associated with increased alloimmunization against human leukocyte antigens

Alloantibodies recognizing human leukocyte antigens (HLA) can cause immune-mediated refractoriness to platelet transfusion. An association between HLA alloimmunization and red blood cell (RBC) alloimmunization has been suggested but remains uncertain.

We tested for HLA alloantibodies in 660 patients with and without RBC alloantibodies. Calculated panel reactive antibody (cPRA) values were determined for HLA alloimmunized patients. Current and historical diagnoses and blood product exposure were catalogued. Variables associated with high-level HLA alloimmunization (cPRA ≥ 90%) were evaluated.

The cohort included 366 women and 294 men with median age of 66 years (interquartile range [IQR], 53-76). The number of patients with and without RBC alloantibodies was 447 and 213, respectively. Among patients with and without RBC alloantibodies, 20.6% and 8.5% had a cPRA ≥ 90%, respectively (p < 0.0001). In univariate analyses of men and nulliparous women and previously pregnant women, the median number of RBC alloantibodies was significantly higher in patients with a cPRA ≥ 90% (p < 0.0001). The number of RBC alloantibodies remained an independent predictor of a cPRA ≥ 90% in multivariate analysis (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.22-1.85). Other independent predictors of a cPRA ≥ 90% were parity (OR 1.26, 95% CI 1.08-1.47), age (OR 0.98, 95% CI 0.97-1.00), history of renal disease (OR 1.88, 95% CI 1.02-3.48), and number of non-leukoreduced products transfused (OR 1.02, 95% CI 1.00-1.04).

RBC alloimmunization was significantly associated with HLA alloimmunization with a cPRA ≥ 90%. RBC alloimmunization status combined with specific components of the clinical history may estimate the risk of high-level HLA alloimmunization.