International Internal Medicine Journal(IIMJ)
ISSN: 2837-4835 | DOI: 10.33140/IIMJ
Impact Factor: 1.02
Short Article - (2026) Volume 4, Issue 1
Functional Anaemia in Homozygous δβ-Thalassaemia Lepore Identified via HPLC
2Hematology Laboratory Department Hippokrateio General Hospital of Athens, 114 Vas. Sofias Ave, Athens, Greece, 11527, Greece
Received Date: Jan 01, 2026 / Accepted Date: Jan 22, 2026 / Published Date: Jan 30, 2026
Copyright: ©2026 Sophia Delicou, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation: Delicou, S. Bristogiannis, S., Xydaki, K., Moraki, M., Kozanitou, M. (2026). Functional Anaemia in Homozygous ??-Thalassaemia Lepore Identified via HPLC. Int Internal Med J, 4(1), 01-03.
Abstract
A 55-year-old male with a DNA diagnosis of homozygous δβ- thalassemia Lepore (δβLepore/δβLepore), who had a splenectomy at age 20 due to hypersplenism, presented with gradually worsening fatigue. He maintained transfusion independent for a period of three decades, with haemoglobin levels ranging from 11.5 to 12 g/dL.
Introduction
A 55-year-old male with a DNA diagnosis of homozygous δβ-thalassemia Lepore (δβLepore/δβLepore), who had a splenectomy at age 20 due to hypersplenism, presented with gradually worsening fatigue. He maintained transfusion independent for a period of three decades, with haemoglobin levels ranging from 11.5 to 12 g/dL.
On evaluation, he was clinically stable but reported reduced fatigue. Laboratory investigation showed hemoglobin 10.2 g/dL (reference 13.5–17.5), hematocrit 31.5% (41–53), mean corpuscular volume (MCV) 85.5 fL (80–96), mean corpuscular hemoglobin (MCH) 25.5 pg (27–33), red cell distribution width (RDW) 22.9% (11.5– 14.5), reticulocyte count 6.9% (0.5–2.5), ferritin 470 ng/mL (30– 300), lactate dehydrogenase (LDH) 310 U/L (<250), and indirect bilirubin 1.6 mg/dL (0.2–1.2).
High-performance liquid chromatography (Bio-Rad Variant II) had been used to perform haemoglobin analysis, which revealed a complete absence of HbA and a significant increase in HbF (83.6%) and HbA2 (12.8%). A minor peak was detected in the S-window (2.8% at 3.45 minutes) representing δβ hybrid chains rather than HbS, a known analytical artifact in δβ-thalassaemia.
Given the high oxygen affinity of HbF, only HbA2 is traditionally considered physiologically effective. Thus, functional hemoglobin was initially estimated as:
10.2 g/dL × 0.128 = 1.31 g/dL
However, if we assume that a portion of HbF (e.g., 30%) contributes to oxygen delivery, a revised estimate of functional hemoglobin can be calculated:
10.2 g/dL × (0.128 + 0.30 × 0.836) ≈ 10.2 × 0.379 = 3.87 g/dL
To estimate total functional hemoglobin, each fraction is multiplied by its presumed oxygen-delivering efficiency.In this model, HbA2 gives a weight of 100%, while HbF is provided a functioning weight of 30%. The total of these contributions delivers the overall effective haemoglobin concentration [1].
This suggests that partial HbF activity may yield a more realistic representation of effective oxygen-carrying capacity, yet still insufficient to meet physiologic demands. Literature supports that although HbF has high oxygen affinity, it may still contribute to oxygen delivery under certain compensatory conditions such as chronic anemia and reduced 2,3-BPG binding
The primary clinical question in this case was whether transfusion was warranted. Despite preserved total hemoglobin, the patient’s symptoms reflected significant functional anaemia. In the absence of clinical decompensation, transfusion was not pursued. According to current practice, transfusions in non–transfusion-dependent thalassaemia are reserved for specific clinical indications such as pregnancy, cardiac strain, or severe symptomatology [2]. This case also highlights an important clinical paradox relevant to current gene therapy strategies in β-thalassemia. While many gene therapy approaches aim to increase HbF production as a therapeutic target to compensate for defective adult hemoglobin , this patient demonstrates that elevated HbF levels alone may not ensure adequate oxygen delivery. Despite achieving HbF levels of 83.6% -a concentration that would be considered a therapeutic success in gene therapy trials-the patient experienced clinically significant functional anemia with symptomatic fatigue. This observation underscores that the high oxygen affinity of HbF, while beneficial in utero, translates to impaired oxygen release in peripheral tissues under physiologic conditions . Therefore, therapeutic strategies must consider not only the quantity of hemoglobin produced but also its functional oxygen-carrying capacity.
Comment:
High-Performance Liquid Chromatography (HPLC) is crucial for the diagnostic assessment of hemoglobinopathies, permitting both the identification and measurement of functionally active haemoglobin [3]. In cases with homozygous δβ-thalassemia Lepore, functional haemoglobin may be significantly decreased despite almost normal total levels. It is essential to recognise the difference in order to achieve the most optimal clinical management.
Figure 1: HPLC Chromatogram Showing a Dominant HbF Peak and Elevated HbA2; HbA isAbsent. Minor Peak in the S-window (3.45 min), Consistent with δβ Hybrid Chains
References
- Zhou Y, Liu J, Chen X, et al. Functional contribution of fetal hemoglobin in adult patients with compound hemoglobinopathies: implications for transfusion strategies. Br J Haematol. 2024;206(4):577–586.
- Taher, A. T., Musallam, K. M., & Cappellini, M. D. (2023).Guidelines for the Management of Non-Transfusion-Dependent β-Thalassaemia.
- Giordano, P. C. (2013). Strategies for basic laboratory diagnostics of the hemoglobinopathies in multiâ?ethnic societies: interpretation of results and pitfalls. International Journal of Laboratory Hematology, 35(5), 465-479.