Background/Case Studies: Beta-thalassemia major is a heritable hemoglobin disorder caused by a homozygous mutation on the beta-globin gene, leading to absent or reduced synthesis of normal hemoglobin, reduced red blood cell (RBC) survival and the need for frequent transfusions. Individuals with beta-thalassemia are thought to exhibit lower glycated hemoglobin (HbA1c) concentration, a common screening method for diabetes. Although it is not recommended to measure HbA1c in beta-thalassemia patients due to its inaccuracy, a 20-year-old splenectomized male with transfusion-dependant beta-thalassemia demonstrated elevated HbA1c levels despite normal random glucose, fasting glucose, and a 2-hour oral glucose tolerance test; this prompts questions about the impact of transfusions on HbA1c levels. This study aimed to assess whether transfusions can cause falsely elevated HbA1c.
Study
Design/Methods: The patient was transfused once every two weeks and had weekly blood collections. Whole blood samples were used for Percoll density separation to isolate biologically young (less dense; represents donor’s RBCs) and old (more dense; represents recipient’s RBCs) RBC subpopulations. Percoll density was estimated using the mean corpuscular hemoglobin concentration of the RBCs. Percoll densities of 1.096 and 1.101 g/mL were used to isolate the top and bottom 15-25% of the young and old RBCs, respectively. HbA1c was measured using Tina-Quant HbA1c assay on Roche Cobas c513 analyzer for unseparated, young, and old RBC populations weekly to track changes from one-day pre-transfusion (n=13) to day 6 (n=11) and day 13 (n=12) post-transfusion. The differences were assessed using Bonferroni’s multiple comparison and Augmented Dickey-Fuller tests.
Results/Findings: The HbA1c between the subpopulations and unseparated samples were significantly different (p< 0.001), where old RBCs (the recipient’s RBCs) had the highest HbA1c levels and young RBCs (donor’s RBCs) had the lowest HbA1c levels. HbA1c decreased following transfusions at day 6 post-transfusion with an average decrease of 0.10 ± 0.11% (unseparated RBCs), 0.35 ± 0.34% (young RBCs; p< 0.05) and 0.19 ± 0.20% (old RBCs). From day 6 to day 13 post-transfusion, HbA1c increased by 0.16 ± 0.44% in young RBCs. Conclusions: This case demonstrates transfusion-dependent changes to HbA1c measurements, most notable at day 6 post-transfusion in the youngest RBCs. As these RBCs are thought to be representative of the transfused donor RBCs, this prompts further investigation into factors such as donor age, sex, diabetic status, and storage conditions on the distribution of RBC age in a blood product and their HbA1c levels as they can influence post-transfusion HbA1c levels.
