Thalassemia syndromes and iron deficiency anemia (IDA) are the two most common etiologies of microcytic hypochromic anemia in children and adults. It has long been considered that iron deficiency does not exist in thalassemia syndromes, including thalassemia major as well as trait. However, studies have shown the occurrence of iron deficiency in patients with beta thalassemia trait (BTT). Earlier authors have demonstrated lower initial hemoglobin levels in patients with coexisting IDA and BTT [
HbA2 levels have been reported to be lower in patients with coexisting IDA and BTT, with improvement in levels after iron therapy [
An extensive search of the available indexed English literature yielded only few Indian reports of concomitant BTT and iron deficiency [
The present study aimed at an extensive analysis of the effect of iron therapy on various red cell parameters and iron status in patients with concomitant IDA and BTT in our country. The study was approved by the institutional ethics committee.
This prospective study included patients attending the hematology clinics of departments of pediatrics and medicine at a tertiary care centre over a period of two years (Dec 2006–Nov 2008). Patients with HbA2 levels >3.7% with low serum ferritin (<10 ng/mL for females and <16 ng/mL for males), normal random blood sugar levels, and no evidence of other hemoglobinopathy were included in the study. Cases with lower HbA2 levels, other hemoglobinopathies, abnormal blood sugar levels, and normal or high ferritin levels were excluded from the study. Written informed consent was taken from the patients/guardian (in case of pediatric patients).
All the included patients underwent complete blood counts using an automated hematology analyzer, thalassemia screening by high performance liquid chromatography (HPLC) using BIORAD Variant hemoglobin testing system (BIORAD Laboratories, Hercules, USA), and serum iron studies, including serum iron and total iron binding capacity, TIBC using a kit (POINTE SCIENTIFIC Inc., USA), and serum ferritin by a microtiter ELISA kit (DiaMed EuroGen, Belgium).
After the initial investigations, these patients were initiated on oral iron therapy (tab ferrous sulphate: children 1.5–2 mg/kg body weight elemental iron tds; adults 60 mg/day elemental iron tds) for twenty weeks. On completion of therapy, all the investigations were repeated.
The pre- and posttherapy data was analyzed using appropriate statistical tests. The change in hematological parameters, serum iron, TIBC, and hemoglobin subtypes were analyzed using paired “
Over the study period, 30 patients of BTT with concomitant iron deficiency were included. Majority of our patients (28, 93.3%) were adults with a mean age of
The mean hemoglobin level was
Pre- and posttherapy hematological and biochemical parameters.
Parameter | Pretherapy | Posttherapy |
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Hemoglobin (g/dL) |
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RBC count (million/mm3) |
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0.35 |
Mean corpuscular volume, MCV (fL) |
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Mean corpuscular hemoglobin, MCH (pg) |
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Mean corpuscular hemoglobin concentration |
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Red cell distribution width, RDW-CV (%) |
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Serum iron ( |
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TIBC ( |
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Ferritin (ng/mL)* | 6.75 | 25.9 |
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(QD 1.175) | (QD 10.96) | ||
HbF (%) |
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0.98 |
HbA2 (%) |
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HbF values ranged from 0.0 to 3.7% (mean
The mean hemoglobin level rose to
HbF levels remained largely unchanged after iron therapy while HbA2 values showed significant rise after therapy (
Graphs demonstrating the change in hemoglobin values (a), serum iron (b), HbA2 levels (c), and TIBC values after iron therapy.
Peripheral smear from a patient with concomitant iron deficiency and beta thalassemia trait before iron therapy (a, Giemsa ×400). HPLC graph of the same patient before iron therapy (b). Peripheral smear of the same case as in an after iron therapy (b, Giemsa ×400). HPLC graph of the same patient after iron therapy (d).
Iron deficiency anemia and thalassemia syndromes, especially beta thalassemia trait (BTT), are the two most frequent microcytic hypochromic anemias highly prevalent in countries like India [
Iron status in BTT has been an area of interest for many authors. Due to the frequent iron overload in thalassemia major patients, it was earlier believed that iron deficiency does not exist in BTT also. However, a study by Alperin et al. in 1976 included 33 patients of BTT with evidence of iron deficiency and showed lower initial hemoglobin levels, which improved after iron replacement therapy [
The parameters of iron status, as expected, improved after sufficient iron replacement therapy. In our patients, serum iron increased significantly with values reaching the normal range. TIBC, which was high prior to iron therapy, normalized indicating good compliance to iron therapy. We used serum ferritin levels <15 ng/mL as a cutoff for iron deficiency, as in previous studies [
Among hemoglobin subtypes, HbF values did not show any significant change after iron therapy. This is similar to previous studies by El-Agouza et al. and Wasi et al. [
HbA2 levels, in our patients, improved significantly after iron replacement therapy. Similar results have been reported by earlier authors [
An extensive search of the available indexed English literature yielded only few Indian reports of concomitant BTT and iron deficiency [
A recent study from Pakistan reported low HbA2 levels in BTT with concomitant iron deficiency leading to diagnostic difficulties. The authors suggested that such patients, who may be diagnosed as normal on hemoglobin electrophoresis or HPLC, could marry a person with BTT and lead to birth of children with beta thalassemia major. Such an occurrence poses a serious hindrance for the thalassemia prevention program. Hence, the authors concluded that coexisting pathological conditions should be identified before reporting the hemoglobin electrophoresis or HPLC as normal, especially in countries with high incidence of both iron deficiency and BTT [
In conclusion, the present study highlights the coexistence of iron deficiency anemia and beta thalassemia trait in Indian patients. The diagnosis of beta thalassemia trait in such patients may be confounded by reduction in HbA2 levels. Hence, iron deficiency should be identified and corrected in patients with high suspicion of beta thalassemia trait, especially if HbA2 levels are within normal range.
The authors declare no conflict of interests. The authors alone are responsible for the content and writing of the paper.