Frequent blood donations alter susceptibility of red blood cells to storage- and stress-induced hemolysis

Abstract

Background: Frequent whole blood donations increase the prevalence of iron depletion in blood donors, which may subsequently interfere with normal erythropoiesis. The purpose of this study was to evaluate the associations between donation frequency and red blood cell (RBC) storage stability in a racially/ethnically diverse population of blood donors.

Study design: Leukoreduced RBC concentrate-derived samples from 13,403 donors were stored for 39 to 42 days (1-6°C) and then evaluated for storage, osmotic, and oxidative hemolysis. Iron status was evaluated by plasma ferritin measurement and self-reported intake of iron supplements. Donation history in the prior 2 years was obtained for each subject.

Results: Frequent blood donors enrolled in this study were likely to be white, male, and of older age (56.1 ± 5.0 years). Prior donation intensity was negatively associated with oxidative hemolysis (p < 0.0001) in multivariate analyses correcting for age, sex, and race/ethnicity. Increased plasma ferritin concentration was associated with increased RBC susceptibility to each of the three measures of hemolysis (p < 0.0001 for all), whereas self-reported iron intake was associated with reduced susceptibility to osmotic and oxidative hemolysis (p < 0.0001 for both).

Conclusions: Frequent blood donations may alter the quality of blood components by modulating RBC predisposition to hemolysis. RBCs collected from frequent donors with low ferritin have altered susceptibility to hemolysis. Thus, frequent donation and associated iron loss may alter the quality of stored RBC components collected from iron-deficient donors. Further investigation is necessary to assess posttransfusion safety and efficacy in patients receiving these RBC products.

Figure 1:

Flowchart of the RBC-Omics study cohort and donor testing for hemolysis and ferritin.

Figure 2:. RBC-Omics donor age (years±SD) at selected categories of donation frequency in the 24 months prior to enrollment.

Asterisks represent statistical significant difference in age (p < 0.001).

Figure 3:. Sex distribution of stress-induced hemolysis, storage hemolysis or donor ferritin levels at selected categories of donation frequency in prior 24 months.

RBC concentrates from male or female donors ages 18–90 years old were stored (1–6°C) for 39–42 days in transfer bags and tested for storage or stress-induced hemolysis as described in Materials and Methods. A. Percent AAPH-induced oxidative hemolysis (150mmol/L, 1.5h, 37°C) (n=10,476). B. Percent osmotic hemolysis (n=12,799). C. Percent spontaneous storage hemolysis (n=12,753). D. Donor plasma ferritin (ng/mL) (n=13,323). Error bars represent standard errors of the mean. Asterisks represent statistical significant difference in mean hemolysis or ferritin between first- time/reactivated donors and each of the donation frequency bin for male and female (p < 0.001). Hemolysis measures were normalized for blood center differences in blood component manufacturing procedures.

Figure 4:. Evaluation of age-specific differences in the rates of stress or storage-induced hemolysis in response to frequent blood donations.

Figure panels represent the amount of A. Percent AAPH-induced oxidative hemolysis (150mmol/L, 1.5h, 37°C) (n=10,476). B. Percent osmotic hemolysis (n=12,799), and C. Percent storage spontaneous hemolysis (n=12,753) at selected age groups (decades) in the 4 categories of donation frequency. Error bars represent standard errors of the mean. A. n=17 and B-C. n=25 young donors (<21 years) at donation categories 5–8 and 9+ combined. Hemolysis measures were normalized for blood center differences in blood component manufacturing procedures.

Figure 5:. Association of self-reported iron intake with RBC predisposition to stress-induced hemolysis, storage hemolysis or donor ferritin levels.

Data obtained from male (M) and female (F) RBC-Omics donors who responded Yes (Y) or No (N) to the consumption of iron supplements. A. Percent AAPH-induced oxidative hemolysis (150mmol/L, 1.5h, 37°C), B. Percent osmotic hemolysis, C. Percent storage spontaneous hemolysis, and D. Donor ferritin levels (ng/mL). Error bars represent standard errors of the mean at the 4 categories of donation frequency. Asterisks represent statistical significant difference in mean hemolysis or ferritin by iron intake status stratified by donation history and sex (p < 0.001). Hemolysis measures were normalized for blood center differences in blood component manufacturing procedures.