Menoufia Medical Journal

ORIGINAL ARTICLE
Year
: 2021  |  Volume : 34  |  Issue : 1  |  Page : 197--203

Detection of thalassemia trait and iron-deficiency anemia among relatives of thalassemic patients – Menoufia Governorate


Seham M Ragab1, Mohamed A Soliman2, Sameh A Abd El Naby1, Amr Mohammed R.I. Nassar3,  
1 Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Pediatrics, Ministry of Health, Tala, Menoufia, Egypt

Correspondence Address:
Amr Mohammed R.I. Nassar
Department of Pediatrics, Ministry of Health, Tala, Menoufia
Egypt

Abstract

Objective To detect thalassemia trait and iron-deficiency anemia (IDA) among children relatives of thalassemic patients. Background Beta-thalassemia represents a major public health problem in Egypt. β-thalassemia trait (BTT) often shows microcytosis and an elevated level of hemoglobin A2. Despite the start of iron fortification, the prevalence of iron deficiency is still rather high in the Middle East countries. Patients and methods A cross-sectional study was conducted on 200 pediatric relatives of β-thalassemic pediatric patients attending the Hematology Unit of the Pediatric Department, Menoufia University Hospitals, during the period from October 2015 to April 2018. Full history, clinical examination, complete blood count, serum iron, serum ferritin, and total iron-binding capacity were investigated. Results Overall, 20.5% of patients had BTT and 12.5% had IDA. However, 66 (33%) of the studied children had microcytic hypochromic anemia. Pallor was found in 40.9% of total group, pica found in 19.7%, and easy fatigue in 25.8% of them. All IDA cases responded to oral iron therapy. Conclusion The frequency of BTT among pediatric close relatives of thalassemic patients is higher than in general population. IDA group had significantly higher Mentzer, Sirvastava, England and Fraser, Sirdah, Shine and Lal scores than BTT groups. BTT group had significantly higher red blood cells count, serum iron, serum ferritin, and hemoglobin A2 than IDA group. IDA group had significantly higher mean cell volume, mean cell hemoglobin, red cell distribution width, total iron-binding capacity, and hemoglobin A than BTT groups.



How to cite this article:
Ragab SM, Soliman MA, Abd El Naby SA, Nassar AM. Detection of thalassemia trait and iron-deficiency anemia among relatives of thalassemic patients – Menoufia Governorate.Menoufia Med J 2021;34:197-203


How to cite this URL:
Ragab SM, Soliman MA, Abd El Naby SA, Nassar AM. Detection of thalassemia trait and iron-deficiency anemia among relatives of thalassemic patients – Menoufia Governorate. Menoufia Med J [serial online] 2021 [cited 2021 Aug 4 ];34:197-203
Available from: http://www.mmj.eg.net/text.asp?2021/34/1/197/312005


Full Text



 Introduction



β-thalassemia major is a serious health problem, in which children are in need of regular blood transfusions from a very young age to survive [1]. They also need to receive iron chelation therapy to remove excess iron from their bodies, which imposes serious risk on their health and quality of life (QOL) [2]. Patients with β-thalassemia have poor QOL. High hemoglobin level and low iron overload were associated with improved QOL scores [3]. β-thalassemia trait (BTT) often shows microcytosis, a normal or an increased red blood cell (RBC) count, and an elevated level of hemoglobin A2 (HbA2), which provide the basis for laboratory screening. BTT is an important differential diagnosis of iron-deficiency anemia (IDA). The cutoff values of mean cell volume (MCV) 73 fl or less, RBC count above 5 × 10 6/mm3, and red blood cell distribution width (RDW) 14.5% or less were suggested to be associated with a high probability of BTT [4]. RDW is an automated laboratory determination of RBC anisocytosis. Evaluation of RDW as screening test to detect microcytic anemia had sensitivity of 71.42% and specificity of 40%, and evaluation of RDW as a screening test for IDA had sensitivity of 67.9% and specificity 25%. There was uniform increase in RDW in all cases of microcytosis. It has been concluded that RDW adds useful but limited information in classifying microcytic anemia [5]. Iron deficiency is considered to be the main cause for anemia: it is responsible for more than 50% of all cases. Iron deficiency results, amongst others, in impaired activity of several enzymes. Therefore, iron depletion may result in serious health problems such as retarded growth, mental irritability, reduced resistance to infection, and impaired intellectual development, particularly in case of infants in the growth phase [6]. Despite the start of iron fortification, the prevalence of iron deficiency is still rather high in the Middle East countries. The prevalence of IDA in the Middle Eastern countries is equal to the prevalence in developing countries (25–35%), which is much higher than in industrial countries [7]. Hemocytometric parameters like RBC count, MCV, reticulocyte count, RDW-SD, and zinc protoporphyrin are frequently established for discrimination between IDA and thalassemia in patients with microcytic erythropoiesis. However, no single marker or combination of tests is optimal for discrimination between IDA and thalassemia. This is the reason why many algorithms have been introduced [8]. The aim of this study was to detect thalassemia trait and IDA among children relatives of thalassemic patients.

 Patients and methods



A cross-sectional study was performed on 200 pediatric relatives of β-thalassemic pediatric patients attending at Hematology Unit of the Pediatric Department, Menoufia University Hospitals. This study was done over the period from October 2015 to April 2018.

Ethical consideration

The study was approved by the ethical committee of Menoufia Faculty of Medicine, and an informed consent obtained from all patients' guardians before the study was commenced.

Study group

The study included 200 children who were close relatives of β-thalassemic patients. Complete blood count and blood film were done for all participants.

Selected group

For those with microcytic hypochromic anemia, iron profile and high-performance liquid chromatography were done.

Inclusion criteria

The following were the inclusion criteria: age from 6 months to 5 years, both male and female children, Hb level more than 2 SD below the mean for age and sex and with cutoff point of 11 g/dl, and MCV and mean cell hemoglobin (MCH) levels more than 2 SD below the mean for age and sex with microcytosis with cutoff point 75 fl for MCV.

Exclusion criteria

Children who were previously diagnosed as having chronic hemolytic anemia, children with normocytic normochromic and macrocytic anemias, and patients with a history of acute or chronic illnesses were excluded from the study.

Methods

The first stage was performed on 200 children who were relatives of thalassemic patients who attended the outpatient clinic in the duration from October 2015 to April 2018. These children were screened for microcytic hypochromic anemia by complete blood count using Sysmex KX-21 automatized hematology analyzer (Sysmex Corporation, Japan) 1 Chome-5-1 Wakinohamakaigandori, Chuo Ward, Kobe, Hyogo 651-0073, Japan. Anemia was diagnosed when Hb less than 11 g/dl. Microcytosis and hypochromia were diagnosed when MCV and MCH levels more than 2 SD below the mean for age and sex with microcytosis with cutoff point 75 fl for MCV.

The second stage included all children with microcytic hypochromic anemia, representing 66 cases. They were subjected to the following: full history taking, clinical evaluation (anthropometric measurements, general examination, and abdominal examination), and laboratory investigations, including iron profile [serum iron, total iron-binding capacity (TIBC), and serum ferritin] using ELISA Kit 'EIA-01-Ferritin' (New England Immunology Associates Inc., Cambridge, Massachusetts).

This stage was performed for microcytic hypochromic anemic children who could not be diagnosed by stage 2, representing 41 children. These children were subjected to the following test to search for thalassemia trait cases: high-performance liquid chromatography, which diagnosed 41 cases of BTT.

Statistical analysis

Results were tabulated and statistically analyzed by using a personal computer using Microsoft Excel 2016 and SPSS version 21 (SPSS Inc., Chicago, Illinois, USA). Statistical analysis was done using descriptive, for example, percentage, mean, and SD, and analytical, including χ2, t test, Mann–Whitney test, and receiver operating characteristic curve. A value of P less than 0.05 was considered statistically significant.

 Results



In the current study, there were no statistically significant differences between IDA and BTT groups regarding age, weight, height, and sex (P > 0.05). There were statistically highly significant differences between IDA and BTT groups regarding consanguinity (P < 0.0001) [Table 1].{Table 1}

Moreover, there were statistically highly significant differences between IDA and BTT groups regarding pica and bad dietary habits (P < 0.001 for each). There were statistically significant differences between IDA and BTT groups regarding easy fatigue (P = 0.046), and past history of iron intake (P = 0.004). There were no statistically significant differences between IDA and BTT groups regarding pallor, jaundice, change in color of urine and stool, previous surgery, past history of blood transfusion, and palpable liver and spleen (P > 0.05) [Table 2].{Table 2}

The present study showed that BTT group had significantly higher RBCs count, serum iron, serum ferritin, and HbA2 than IDA group. IDA group had significantly higher MCV, MCH, RDW, TIBC, and HbA than BTT groups. There were no statistically significant differences between IDA and BTT groups regarding hematocrit, platelet count, white blood cells, Hb, and HbF (P > 0.05) [Table 3].{Table 3}

Moreover, IDA group had significantly higher Mentzer, Sirvastava, England and Fraser, Sirdah, and Shine and Lal index scores than BTT groups. There were no statistically significant differences between IDA and BTT groups regarding Ricerca index and Green and King index scores (P > 0.05) [Table 4].{Table 4}

 Discussion



In our results, 20.5% had BTT and 12.5% had IDA. However, 66 (33%) of the studied children had microcytic hypochromic anemia. The study by Soliman et al. [4] found that the prevalence of BTT was 6%, whereas IDA represented 4.5% of total 200 samples investigated. In a Yemeni study by Al-Nood [9], BTT was detected in 31 patients, representing 4.43% of all tested samples and 30% of microcytic samples. In the study by Ali et al. [10], of the 181 patients studied, diagnosis of BTT was made in 10 (5.5%) patients. The study by Parthasarathy [11] found IDA in 120 samples, representing 60% of their study population. In the current study, pallor was found in 40.9% of total group, pica was found in 19.7%, and easy fatigue in 25.8% of them. None of them had jaundice, hepatosplenomegaly, or change in color of urine or stool. The study done by Yadav and Chandra [12] showed that pallor was found in 81.5% of total group, and pica was found in 47% of them. None of them had jaundice, hepatosplenomegaly, or change in color of urine or stool. Various forms of pica have been associated with iron deficiency, including pica for clay or dirt, starch, or raw rice. Moreover, Carvalho et al. [13] found that pica occurs variably in iron and zinc deficiency but is neither sensitive nor specific to the problem, so is of little diagnostic help. The present study showed that BTT group had significantly higher RBCs count, serum iron, serum ferritin, and HbA2 than IDA group. IDA group had significantly higher MCV, MCH, RDW, TIBC, and HbA than BTT groups. There were no statistically significant differences between IDA and BTT groups regarding hematocrit, platelet count, white blood cells, Hb, and HbF. Supporting our results, Yaish et al. [14] found that the RBC count is almost always higher in patients with thalassemia trait than in those with IDA. Moreover, Abdel-Rasoul et al. [15] found that the values of MCV and MCH were decreased in thalassemia patients as compared with patients with iron deficiency. Another study done by Soliman et al. [4] found that IDA group showed a highly significant reduction in their mean Hb levels when compared with the normocytic group, whereas the mean Hb of the BTT group showed no significant difference compared with the normocytic group. A lower mean value of MCV for the BTT group than the IDA group was detected with highly significant statistical difference. In addition, MCV less than 73 was able to differentiate between the two groups with 91.7% sensitivity and 100% specificity. RBCs count showed a highly significant elevation in BTT than in IDA. The study by Mousa et al. [16] reported that RDW can be considered significant in differentiating between IDA and BTT. Nesa et al. [17] found that RDW can be used as an index for screening of BTT. Moreover, Piplani et al. [18] found that RDW was elevated in both the groups, though it was slightly higher in the IDA group. Trivedi and Shah [19] found that RDW-SD is significant in differentiating between IDA and BTT. However, Hoffmann et al. [20] found that RDW had low value in differentiating between BTT and IDA. However, El-Agouza et al. [21] reported significant increase in HbA2% among their patients following iron therapy, and thus concluded that iron deficiency must be corrected before making any diagnostic or therapeutic decisions based on HbA2 level. In our study, IDA group had significantly higher Mentzer, Sirvastava, England and Fraser, Sirdah, and Shine and Lal scores than BTT groups. However, there were no statistically significant differences between IDA and BTT groups regarding Ricerca index and Green and King index scores. In the study by Singh and Gautam [22] on applying different rules on suspected cases of thalassemia patients, JM England rule proved to be superior among these by having 100% specificity, but sensitivity was less. Shine's rule had sensitivity of 85.7%, but specificity was only 28.6%. So application of Shine's rule detected 71.4% false-positive cases. Mentzer's law had sensitivity and specificity of 71.4 and 57.1%, respectively, and among all other rules, it was more accurate, having good sensitivity and specificity both. Controversy continues regarding the ideal red cell indices and their cutoff values for differentiating BTT and IDA. Kotwal et al. [23] conducted a study with 640 adult patients with microcytosis (MCV <80 fl), plotting receiver operator characteristic curves and recalculating the cutoff values for the Indian setting. The cutoff values of MCV less than 76 fl, RBC count at least 4.9 × 1012/l, and RDW 18% or less were suggested to be associated with a high probability of BTT. However, Parthasarathy [11] in India concluded that cutoff values of MCV below 76 fl, RBC count at least 4.9 × 106/mm3, and RDW 18% or less were suggested to be associated with a high probability of BTT. Another Indian study by Bermejo F et al. [24] had cutoff values of MCV 78.0 fl or less, MCH 28 pg or less, and HbA2 more than 3.8% for BTT diagnosis.

Finally, we noted that there were no similar studies done on relatives' group. and all the previous studies were done to detect thalassemia trait among general pediatric population and not relatives.

 Conclusion



The frequency of BTT among pediatric close relatives of thalassemic patients are higher than in general population. The most common type of anemia present in the studied children is microcytic hypochromic anemia. IDA group had significantly higher Mentzer, Sirvastava, England and Fraser, Sirdah, and Shine and Lal scores than BTT groups. BTT group had significantly higher RBCs count, serum iron, serum ferritin, and HbA2 than IDA group. IDA group had significantly higher MCV, MCH, RDW, TIBC, and HbA than BTT groups. Genetic counseling is the key point to decrease the incidence rate of beta-thalassemia in the next generations.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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