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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 31  |  Issue : 4  |  Page : 741-745

Effect of iron therapy on red cell indices and hemoglobin subtypes on patients with beta-thalassemia trait who developed iron-deficiency anemia: a tertiary center experience


1 Department of Internal Medicine, Clinical Hematology Unit, Faculty of Medicine, Assiut University, Assiut, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt

Date of Submission06-Mar-2019
Date of Acceptance13-Jun-2019
Date of Web Publication18-Aug-2020

Correspondence Address:
Dr Sawsan M Moeen
MD Clinical Hematology, Faculty of Medicine, Assiut University, Assiut, Egypt, Postal code 71515
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejim.ejim_38_19

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  Abstract 


Background The combination of beta-thalassemia trait (BTT) and iron-deficiency anemia (IDA) is an interesting common issue in our country. However, treatment of this condition is challenging.
Objectives This prospective observational study was designed to evaluate the effect of oral iron therapy on red cell indices, iron status, and hemoglobin A2 levels in patients with BTT who developed IDA.
Patients and methods A total of 50 patients with BTT who developed IDA were included. A complete blood count, iron status, and follow-up hemoglobin electrophoresis by high-performance liquid chromatography were done. The patients with BTT received oral iron therapy of 60 mg elemental iron three times/day for a period of 5 months, and the investigations were repeated after 3 and 5 months of treatment.
Results There was a statistically significant increase in hemoglobin level (P<0.001 each), mean corpuscular volume (P<0.001 each), mean corpuscular hemoglobin (P=0.004 and P<0.001, respectively), mean corpuscular hemoglobin concentration (P=0.007 and P=0.001, respectively), serum iron (P<0.001 each), serum ferritin (P<0.001 each), and hemoglobin A2 levels (P=0.001 and P=0.005, respectively), whereas significant decrease in the total iron-binding capacity (P=0.001, and P=0.005, respectively) after the third and fifth month of oral iron therapy.
Conclusion It is important to suspect, recognize, and correct IDA in patients with BTT and to repeat hemoglobin electrophoresis after iron therapy.

Keywords: anemia, beta-thalassemia trait, iron deficiency, serum ferritin


How to cite this article:
Moeen SM, Thabet AF, Thabet MM. Effect of iron therapy on red cell indices and hemoglobin subtypes on patients with beta-thalassemia trait who developed iron-deficiency anemia: a tertiary center experience. Egypt J Intern Med 2019;31:741-5

How to cite this URL:
Moeen SM, Thabet AF, Thabet MM. Effect of iron therapy on red cell indices and hemoglobin subtypes on patients with beta-thalassemia trait who developed iron-deficiency anemia: a tertiary center experience. Egypt J Intern Med [serial online] 2019 [cited 2020 Sep 27];31:741-5. Available from: http://www.esim.eg.net/text.asp?2019/31/4/741/292227




  Introduction Top


Iron-deficiency anemia (IDA) and beta-thalassemia are the most common causes of microcytic hypochromic anemia [1],[2]. In some cases, it is challenging to distinguish IDA from hemoglobinopathy. On the contrary, patients diagnosed with beta-thalassemia trait (BTT) can develop iron deficiency with the subsequent need for iron therapy [3]. However, some studies reported lower hemoglobin levels in patients with coexisting IDA and BTT [1]. Diagnosis of BTT depends on increased levels of hemoglobin A2 (HbA2), which is found at low levels (<3%) in normal healthy individuals and elevated levels (≥3.5%) in BTT [4]. The classical phenotype of heterozygous beta-thalassemia includes high HbA2 level and red cell count a markedly decreased mean corpuscular volume (MCV) (60–75 fl) and mean corpuscular hemoglobin (MCH) levels (18–24 pg) [5]. Deficiency of iron can modulates the synthesis of HbA2 resulting in decreased HbA2 levels [6], making the diagnosis of BTT more challenging. Heterozygous beta-thalassemia is usually silent clinically. So, accurate detection of the carrier is important [5]. Iron deficiency results in changes in red blood cell indices, serum iron, ferritin, and total iron-binding capacity (TIBC) [7]. Moreover, IDA may decrease HbA2 levels and interfere with diagnosis of BTT. There are few studies, about concomitant BTT and iron deficiency [8],[9]. Some of these studies have assessed the effect of iron therapy on hemoglobin subtypes and iron status [10].

The aim of the present study was to evaluate the effect of treatment with oral iron therapy of 60 mg elemental iron three times/day for a period of 5 months on red blood cell indices, iron status, and HbA2 and HbF levels in patients diagnosed as having BTT who developed IDA.


  Patients and methods Top


This prospective observational study included 50 patients diagnosed with BTT who developed IDA (23 females and 27 males). Participants were included in the study if their HbA2 level more than 3.7%, hemoglobin level less than 10 g/dl, low serum ferritin levels less than 12 ng/ml, no evidence of other hemoglobinopathy, and normal random blood sugar levels. Cases with other hemoglobinopathies, have normal or high ferritin level, and refuse to participate in the study were excluded. Patients were invited to participate in the study after explaining objectives and steps of the research to them. The study was approved by the Committee of Medical Ethics of the Faculty of Medicine. Written consents were obtained from all participants. The study patients were recruited from Clinical Hematology Unit, Internal Medicine Department and Health Insurance, from July 2017 till September 2018.

All patients were subjected to full history taking including age, sex, with special stress on nutritional history and family history of thalassemia; thorough clinical examination, with careful assessment of clinical signs relevant to thalassemia such as pallor, jaundice, and splenomegaly; and laboratory assessments.

For all participants, laboratory investigations including complete blood count, serum iron, TIBC, serum ferritin, and hemoglobin electrophoresis were done.

An automated cell counter (ADVIA 120 Hematology System, Siemens, Germany) was used to perform complete blood count. Serum iron and TIBC were determined calorimetrically, and ferritin was measured turbidimetrically by using Hitachi-911 Automatic Analyzer (Boehringer Manheim, Tokyo, Japan) and commercially available kit. Hemoglobin electrophoresis was done by high-performance liquid chromatography by D10 system, where 5 μl of blood was withdrawn and hemolyzed before injection in 1-ml buffer. The analytes are eluated at a flow rate of 2 m/min. There are established windows with specific retention times for the most frequently occurring hemoglobin, and the results of patients were interpreted according to it.

Participants received an oral iron therapy 60 mg three times/day for a period of 5 months, and all laboratory investigations were repeated after 3 and 5 months of oral iron therapy.

Statistical analysis

Data entry and analysis were performed using a statistical software package SPSS. P value less than 0.05 was considered statistically significant. Descriptive statistics as mean and SD were calculated. Test of significance as paired t test was used to compare the mean difference before and after therapy.


  Results Top


This study included 50 patients with BTT who developed IDA (23 females and 27 males). Their mean age was 17.48±0.89 years, body weight was 47.72±3.76 kg, and body height was 156.14±4.29 cm. The baseline demographic and laboratory parameters of the studied patients with BTT who developed IDA are shown in [Table 1].
Table 1 Baseline demographic and laboratory data of the studied 50 patients with beta-thalassemia trait

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In the present study, we found a statistically significant increase in mean levels of hemoglobin (P<0.001), red blood cell indices [MCV (P<0.001 each), MCH (P=0.004 and P<0.001, respectively), and mean corpuscular hemoglobin concentration (MCHC) (P=0.007 and P=0.001, respectively)], serum iron (P<0.001 each), and serum ferritin (P<0.001 each), in patients with BTT who developed IDA after 3 and 5 months of oral iron therapy.

Interestingly, mean HbA2 levels were significantly increased after 3 and 5 months of oral iron when compared with their baseline (P=0.001, P=0.005, respectively). However, there was no significant difference between HbF levels before and after iron therapy. However, a statistically significant decrease of the mean levels of TIBC (P<0.001) and red cell distribution width (P=0.004, P=0.009) was observed after 3 and 5 months of treatment ([Table 2], [Figure 1]a–c).
Table 2 Follow-up of red cell indices, iron status, and hemoglobin A2 levels among studied 50 patients with beta-thalassemia trait after 3 and 5 months of oral iron therapy

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Figure 1 (a) Follow-up of Hb levels of the studied patients with BTT. (b) Follow-up of HbA2 levels of the studied patients with BTT. (c) Follow-up of HbF levels of the studied patients with BTT. BTT, beta-thalassemia trait; HbA2, hemoglobin A2.

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Oral iron therapy was well tolerated with minimal adverse effects, such as abdominal pain and constipation in four (8%) patients and occasional nausea in six (12%) patients, but these adverse effects were tolerated by the patients.


  Discussion Top


IDA and thalassemia traits are common causes of hypochromic microcytic anemia that a clinician faces in the blood picture, so it is important for a hematologist to differentiate between both conditions [11]. Interestingly, both IDA and BTT may present in the same individual, and such cases should be identified and treated properly to improve and recover their anemia [12].

The morphological findings in both IDA and BTT are so close that it is really hard to differentiate [13]. Thus, prompt measures should be taken to prevent and treat anemia in those patients to reduce associated morbidity [14] and to have better quality of life.

Understanding the role of thalassemia trait in iron balance and metabolism is still a hot area need to be explored. Moreover, appropriate evaluation of iron status in patients with BTT is needed [1].

Some studies have reported lower levels of hemoglobin and HbA2 in patients with concomitant IDA and BTT, which improved after oral iron treatment [1],[15], whereas other studies found no significant difference in HbA2 levels in these patients [16].

In the present study, we reported a statistically significant increased mean levels of hemoglobin (P<0.001 each), red blood cell indices [MCV (P<0.001 each), MCH (P=0.004 and P<0.001, respectively), MCHC (P=0.007 and P=0.001, respectively);; serum iron (P<0.001 each), and serum ferritin (P<0.001 each) in patients diagnosed with BTT who developed IDA after 3 and 5 months of oral iron therapy.

Moreover, in this study, we reported a significant elevation of mean HbA2 levels after 3 and 5 months of oral iron therapy (P=0.001 and P=0.005, respectively). However, there was no statistically significant difference in HbF levels between before and after oral iron therapy (P=0.112 and P=0.697, respectively).

These results are in concordance with the study by Verma et al. [10], who found a significant increased mean levels of hemoglobin of the studied 20 patients with BTT with concomitant IDA after oral iron therapy for a period of 20 weeks (P<0.001). Additionally, increased mean levels of MCV (P=0.01), MCH (P=0.04), MCHC (P=0.04), serum iron (P<0.001), and serum ferritin (P<0.001) were noted, and they added that assessment of iron status in patients with BTT becomes more interesting, as formerly iron overload had been found in patients with thalassemia major, but lately iron deficiency was found in patients with BTT.

Our results are in similar to those of Dolai et al. [1], who assessed iron levels among Indian patients with BTT (n=150). Of 150 patients with BTT, 29 patients had IDA. Those patients with BTT who had iron deficiency had lower levels of hemoglobin (9.78±0.19) and MCH (20.18±0.4) compared with those patients without IDA (P<0.0, for each). Hence, they concluded that iron deficiency is a common existing condition in BTTs. Moreover, the study suggested that assessment of iron level among patients with BTT should be done and iron deficiency if detected should be treated. Patients with BTT have severe IDA, and if recognized and treated, they will have better prognosis. Moreover, Saraya et al. [17] found iron deficiency in patients with BTT, and they suggested that, iron deficiency in patients with BTT may leads to lack of hematopoietic nutrients as well as imbalance in globin chain synthesis, resulting in further reduction in hemoglobin production.

Similar findings were reported by Hinchliffe and Lilleyman [18], who analyzed the frequency of coincident iron deficiency and BTT, and they reported that, the two can coexist. They also suggested that BTT does not prevent ID.

However, in a study by Mehta and Pandya [19], it was observed that patients with BTT had an advantage of maintained iron balance. They suggested that BTT produces slight ineffective erythropoiesis associated with increased iron absorption. Thus, it is likely to give some degree of protection against deficiency of iron.

In a study by Hoorfar et al. [20], who assessed iron status in patients with BTT, they stated that BTT may play a role in improving iron status in females, but in men, it can lead to iron overload. They concluded that, iron level should be examined in patients with BTT especially in men, to avoid iron overload.

Our results are in agreement with Arshad et al. [15], who studied the effect of iron deficiency in patients with BTT (n=23) on HbA2 levels, and the selected patients had lower initial levels of serum ferritin less than 20 ng/ml, and HbA2 levels were less than 3.5%. They added that lower levels of HbA2 were observed in association with iron deficiency in their patients with BTT. They suggested that the presence of iron deficiency in BTT may mask the diagnosis of BTT.

Consistent with our results, a previous study by El-Agouza et al. [7] analyzed the effect of IDA on the levels of Hb, MCV, MCH, serum ferritin, HbA2, and HbF in patients with BTT with IDA (n=4), where patients were treated with oral ferrous sulfate (325 mg/day) for a period of 20 weeks. They reported a significant increased levels of Hb (10.96±1.12 before and 13.20±0.65 after treatment, P<0.001), MCV (72.38±5.15 before and 81.30±5.22 after treatment, P<0.001), MCH (23.35±2.23 before and 25.52±1.70 after treatment, P<0.001), serum ferritin (3.45±1.73 before and 28.77±14.13 after treatment, P<0.001), and HbA2 (1.89±0.45 before and 2.19±0.53 after treatment, P<0.001). However, HbF levels were not significantly different after iron therapy (0.94±0.18 before and 0.95±0.17 after treatment, P>0.05). They concluded that iron deficiency may interfere with diagnostic tests of HbA2, and it must be identified and treated before any diagnostic or therapeutic procedure.Our results are in agreement with a study by Usman et al. [21], which included patients with combined BTT and IDA (n=8). Patients with the copathological conditions of BTT and IDA were treated with oral ferrous sulfate (325 mg/day) for a period of 20 weeks. They reported that patients with combined BTT and IDA responded to treatment with significant increase in HbA2 levels at the end of oral iron therapy.

Consistent with our results, a previous study by Keramati and Maybodi [8] evaluated the effect of iron deficiency on HbA2 levels in patients with BTT and those with coincident BTT and IDA. They found significant differences in HbA2 values between patients with BTT (5.6±0.9%) and patients with coincident BTT and IDA (4.7±1%). They concluded that IDA can decrease HbA2 level, which may interfere with diagnosis especially in cases with coincident IDA and BTT. Thus, when BTT with IDA is suspected, it is better to do hemoglobin electrophoresis after treatment of iron deficiency.

However, Passarello et al. [16] reported that there could be some problems in the presence of silent beta-thalassemia carrier with ID, as HbA2 shows normal levels. They stated that lower levels of hemoglobin and MCV, and persistent low levels of MCV and MCH after iron therapy, required further molecular analysis of α and β genes, especially if the partner is a carrier of BTT.


  Conclusion Top


Our results showed that patients with BTT who developed IDA can successfully treated with oral iron therapy for a better quality of life. Oral iron has a good role in improving anemia by significantly increasing hemoglobin levels, red blood cell indices, serum iron, serum ferritin, and HbA2 levels.

Limitations

The study has some limitations such as the small number of patients with BTT who had IDA.

Recommendations

Further trials with larger number of patients and longer follow-up are recommended.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Karim MUA, Moinuddin M, Babar SU. Cap+ 1 mutation; an unsuspected cause of beta thalassaemia transmission in Pakistan. Turk J Haematol 2009; 26:167.  Back to cited text no. 2
    
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Abdul Hafeez K, Watshara S, Virapong P, Pornlada N. New bioinformatics-based discrimination formulas for differentiation of thalassemia traits from iron deficiency anemia. Lab Med 2017; 48:230–237.  Back to cited text no. 11
    
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Passarello C, Giambona A, Cannata M, Vinciguerra M, Renda D, Maggio A. Iron deficiency does not compromise the diagnosis of high HbA2 β thalassemia trait. Haematologica 2012; 97:472–473.  Back to cited text no. 16
    
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