(P-BC-45) Hiding in Plain Sight: Does Undetected Alpha Thalassemia Contribute to Low Hemoglobin Deferral in Donors with African Ancestry?

Background/Case Studies: Blood collections from African American/Black (AA) donors help provide antigen-matched blood to chronically transfused patients, such as those with sickle-cell disease. AA donors are deferred from donation for low hemoglobin (Hb) at a rate 2-3 times that of White donors. Alpha thalassemia (AT) is an inherited disorder of hemoglobin synthesis associated with impaired production of α-globin chains and resultant lower Hb/mild anemia. Estimated prevalence is 1 in 3 for US residents of African ancestry and is rare (< 1 per 1000) in those with northern European/Caucasian ancestry. Carrier and trait forms of AT (alteration of 1 or 2 α-globin genes, respectively) are considered clinically silent, and the attendant lower Hb values in blood donors could be interpreted as due to donation-related iron deficiency (ID). RBC indices and ferritin can potentially distinguish AT from ID, but these measures are not routinely available in blood donors.

Study

Design/Methods: We re-analyzed enrollment data from the REDS-III RBC Omics population, a large US cohort enriched for racial/ethnic minority donors. Successful enrollment included a productive WB donation, a complete blood count (CBC) performed locally on hematology analyzers, and plasma ferritin batch tested at a central lab. This analysis is restricted to largely unselected non-Hispanic White (NHW) and AA donors at their RBC Omics enrollment visit. CBC parameters were compared between donors with ID (ferritin< 12 ng/mL) in NHW donors and between NHW and AA donors whose ferritin was ≥12ng/mL. We hypothesized that hematological results consistent with AT would be more prevalent in AA than in NHW donors who did not have ID. Statistical tests were not performed.

Results/Findings: A total of 1584 AA donors and 7010 NHW donors were analyzed. In NHW donors, MCV (mean cell volume) was lower in donors with ID (Figure A). In 1378 AA and 5686 NHW donors with ferritin ≥12ng/mL, lower values were more frequent in AA vs NHW donors (Fig. A) for MCV, MCH (mean cell Hb), and MCHC (mean cell Hb concentration). The prevalence of low MCV (< 80fL), low MCH (< 27pg) and low MCHC (< 32g/dL) was greater in AA vs NHW donors without ID: 6.0% in AA vs 0.8% in NHW for MCV, 17.1% in AA vs 2.9% in NHW for MCH, and 29.1% in AA vs 9.9% in NHW for MCHC. Similar discrepancies were found using a ferritin cutoff of 26ng/mL to define ID.

Conclusions: Hematological findings consistent with AT (lower MCV, MCH, MCHC) were found at higher prevalence in AA donors than NHW donors, controlling for iron status. Though molecular testing is required to confirm a diagnosis of AT, the differences observed in donors without ID suggest that AT might be present in AA donors. The high prevalence of ID in blood donors may obscure recognition of other causes of microcytic, hypochromic anemia that contribute to low Hb deferral.