Risks associated with red blood cell transfusions: potential benefits from application of pathogen inactivation

Kleinman, Steve; Stassinopoulos, Adonis

Since PI is known to prevent donor WBCs from exerting their immunologic effects, PI could theoretically affect the immune system's presentation of RBC antigens and thereby influence RBC alloimmunization rates; therefore, the impact of LR on RBC alloimmunization may help predict whether PI treatment of RBC would have a similar effect. [80] [81] [82] The development of RBC alloantibodies has wellknown potential deleterious consequences. The rate of RBC alloimmunization in transfused hospitalized patients (excluding patients with hemoglobinopathies) has been measured at 1.8% and 4% in two large studies. 83, 84 The rate increases with the number of RBC units transfused; however, the majority of antibodies are formed early in the course of transfusion therapy. Specific primary diagnoses are associated with higher rates: 18% to 47% in sickle cell disease (SCD) patients in the absence of phenotypic matching, 85 5% to 30% in thalassemia, 17,86-89 15% in MDS, 90 and 9% in patients with malignant hematology diagnoses. 91 A prospective small randomized control trial in 404 cardiac surgery patients examined the effect of universal LR on RBC alloimmunization. 92 Although the rate was lower in the LR group than in the non-LR group (3.4% vs. 7.1%), the difference was not significant. A smaller singlehospital study using a retrospective noncontemporaneous study design demonstrated a decreased alloimmunization rate in recipients of LR versus non-LR RBCs based on comparing data from two 1-year intervals separated by 14 years. 93 This same study showed that LR resulted in a decreased alloimmunization rate in acute myeloid leukemia patients whereas a different study showed no effect of LR in MDS patients. 90 Other smaller studies in thalassemia patients have suggested an association of LR with a decreased RBC alloimmunization rate; 94 however, these studies have had small sample sizes and have potential confounding factors. In summary, the available data do not allow for a firm conclusion. Unlike LR (which still leaves a small number of viable WBCs in the blood product), 80,81 PI renders WBCs nonviable and stops protein production and antigen expression, thus establishing a theoretical basis for why PI might reduce alloimmunization even if LR does not. 95, 96 Patients with leukemia usually receive both RBC and PLT transfusions. Current data suggest that PI treatment of PLTs may reduce the rate of HLA alloimmunization in this patient group. 96 It is possible that PI-RBCs may show the same benefit. If so, the application of PI to both components may protect against HLA alloimmunization and may improve the odds of finding a compatible HSCT donor for patients with leukemia as well as for patients with hemoglobinopathies who may become future HSCT candidates. 97, 98 These possibilities need to be examined in the clinic.