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ORIGINAL ARTICLE
Year : 2015  |  Volume : 42  |  Issue : 3  |  Page : 170-175

A clinical study of hemoglobin E with special reference to serum ferritin level


1 Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India
2 Department of Medicine, Assam Medical College, Dibrugarh, Assam, India

Date of Web Publication16-Sep-2015

Correspondence Address:
Dr. Umesh Das
Department of Medical Oncology, Room No. 5, OPD Block, Kidwai Memorial Institute of Oncology, Bangalore - 560 029, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-5009.165558

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  Abstract 

Introduction: The spectrum of anaemia is modified in many parts of world, due to prevalence haemoglobinopathies. The common haemoglobinopathies includes HbS, HbC, D (Punjab) and E. In Assam with its population consisting of diverse ethnic groups, is a rich reservoir of abnormal haemoglobin and thalassaemia. The incidence of HbE from various population survey of Assam showed that 20% among Indig Assamese, 57.4% among Ahoms and as high as 80% among Bodo-Kacharis. Iron therapy is hazardous in haemoglobinopathies due to risk of tissue iron toxicity, so needs evaluations of iron status before iron therapy. The size of the stored iron in the body is accurately indicated by serum ferritin estimation, which is single most sensitive and non-invasive method for iron status evaluation. Keeping all in minds the aim of the our study is to study the serum ferritin level of patients with HbE attending AMCH, Dibrugarh.
Materials and Methods: This study was conducted in the department of medicine, AMCH for 1-year. 80 HbE patients of various religions and tribes were selected for study. Patients with HbE having malignancy, end stage renal disease, arthritis, chronic liver disease, and sepsis were excluded from the present study by careful history taking and laboratory investigations. Serum ferritin level was estimated by IRMA technique.
Result and Observation : The incidence of HbE disease (E/E), trait (A/E) and HbE-thalassaemia (E/F) was 47.5%, 42.5%& 10% respectively. Most of the patients were in their second and third decade (57.5%). Male female ratio was 13:7, most being Ahom (60%) and Kochari (12.5%). The haemoglobin concentration in A/E, E/E and E/F were 8.94±0.928, 8.04±0.8840 and 6.02±0.1500; serum ferritin level 24.95±11.90, 162.26±59.5 and 1017±322.19 respectively. E/E patients on blood transfusions have a higher level of serum ferritin (122.85±4.95) than those without transfusions (95.75±9.54). Again those cases of E/F on regular blood transfusions have a higher ferritin (1260±188.14) level than those with occasional transfusions (715±155.80).
Conclusion : Serum ferritin assay IRMA technique is simple and suitable for evaluation of serum iron status. Iron deficiency may be seen among HbE trait but normal or higher serum ferritin in E/E and E/F cases in this study suggests that indiscriminate iron therapy could be harmful in most of the patients without prior evaluation of serum ferritin.

Keywords: Serum ferritin, HbE, HbE trait, HbE disease, HbE thalassaemia


How to cite this article:
Das U, Kakati S, Gogoi GN. A clinical study of hemoglobin E with special reference to serum ferritin level. J Sci Soc 2015;42:170-5

How to cite this URL:
Das U, Kakati S, Gogoi GN. A clinical study of hemoglobin E with special reference to serum ferritin level. J Sci Soc [serial online] 2015 [cited 2022 Dec 1];42:170-5. Available from: https://www.jscisociety.com/text.asp?2015/42/3/170/165558


  Introduction Top


Hemoglobinopathies constitute a imperative causative factor for anemias of childhood and adults. This is especially observed in so in those regions where hemoglobinopathies are prevalent in a higher frequency. They may mimicnutritional anaemia but refractory to the usual corrective measures. Hemoglobinopathies are broadly divided into two groups: One group consists of structural alteration of amino acid sequence in globin chain, and another group consists of thalassaemia syndromes. [1]

The common hemoglobinopathies as per a World Health Organization (WHO) (1972) report includes hemoglobin S (HbS), hemoglobin C (HbC), hemoglobin D (Punjab), and hemoglobin E (HbE). Beta thalassaemia is also prevalent throughout the world in variable frequency. [2]

A broad spectrum of hemoglobinopathies has been documented in India. [3] In Assam with its population consisting of diverse ethnic groups, is a rich reservoir of abnormal hemoglobin and thalassaemia. [4] The frequency of HbE among indigenous Assamese communities varies from 23% to 78%. [5] The incidence of HbE from various populations survey of Assam is 20% among indigenous Assamese, 57.4% among Ahoms, and as high as 80% among Bodo-Kacharis. [6]

HbE was first discovered by Itano, Bergren and Sturgeon in 1954 in a person of Guatemalan origin with Spanish and Hindu ancestry and was the 4 th abnormal hemoglobin variant discovered after HbS, HbC and HbD2. [7] HbE is a beta chain mutant hemoglobin in which glutamic acid B26 is substituted by Lysine. [8] HbE disorders are the most prevalent hemoglobinopathies in Southeast Asia and of the estimated 30 million persons with HbE disorders, more than 80% live on the Southeast Asian mainland. In India, Assam and the neighboring states have been identified as the region where the prevalence of HbE is high.

It is observed that the patient with anemia is always treated with iron supplementation without any investigation. Iron therapy is hazardous in hemoglobinopathies due to the risk of iron toxicity in the tissue, so evaluations of iron status are necessary before iron therapy. The size of the stored iron in the body is accurately indicated by serum ferritin estimation, which is the single most sensitive and non-invasive method for iron status evaluation. Keeping all in minds the aim of our study is to explore the serum ferritin level of patients with HbE attending the Assam medical College and Hospital, Dibrugarh.


  Materials and Methods Top


The present study was carried out at Assam Medical College and Hospital, Dibrugarh, for the period of a year. Both inpatient and outpatients having anemia were enrolled for the study.

Selection of cases

The present study included patients of various religions, tribes, castes, and languages irrespective of their sex. In the anemic cases, patients were either admitted to the wards or treated as outpatients, and electrophoresis of hemoglobin was done on anemic patients who did not respond to usual hematinic therapy. Then, patients with HbE disorders were selected for detailed clinical and hematological study. HbE disorders include HbE disease (HbE/E), hemoglobin E trait (HbA/E) and HbE-thalassaemia (HbE/F). All types of HbE disorder were selected for the study. Patients with a history of blood transfusion were also taken for the study.

Exclusion criteria

Patients with HbE having malignancy, end-stage renal disease, arthritis, chronic liver disease, and sepsis were excluded from the study.

In each case, a thorough history-taking and clinical examinations were done. Various investigations done in all subjects were complete blood counts (CBC), routine examination of urine, peripheral blood film for anisocytosis/poikilocytosis/target cells/basophillia/spherocytes/elliptocytes, malarial parasite, osmotic fragility test, HbElectrophoresis (agarose gel electrophoresis), Alkali denaturation test, Liver function test, radiological-ultrasound (USG) abdomen, and skull, long bone, and chest X-rays. Serum ferritin level was estimated by immunoradiometric assay.


  Results and Observations Top


In the present study, a total 80 cases of HbE disorders (38 HbE/E, 34, HbA/E, and 8 HbE/F) presented with different manifestations were studied in Assam Medical College and Hospital, Dibrugarh for one year.

The relative incidence

The relative incidence of HbE/E in patients presenting with different symptoms was 47.5% and that of HbA/E was 42.5%, while the incidence of HbE/F was found to be 10%.

Age and sex distribution [Table 1]
Table 1: Age distribution of HbE disorders


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The highest number of patients were in their second and third decades of life.

Caste/community distribution [Figure 1]
Figure 1: Bar diagram showing the castes and community distribution


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Most of the patients of HbE disorders were Ahom (60%) and by Kochari (12.5%), reflecting high prevalence of HbE disorders among them.

Haematological findings [Table 2] and [Table 3]
Table 2: Haematological values in HbE disorders


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Table 3: Red cell indices in HbE disorders


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Hemoglobin level in HbA/E patients ranged from 6.9 to 10.4 gm/dl, with total red blood cells (RBC), white blood cells (WBC), and platelet counts were within normal limits. The mean hemoglobin level in HbE/E and HbE/F patients were 7.73 gm/dl and 5.96 gm/dl, respectively. The total RBC count was 2.91 million/cumm. The mean packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) in HbA/E cases was 35.23%, 77.11fl, 23.95 pg and 30.18 gm/dl, respectively. The mean PCV, MCV, MCH, and MCHC in HbE/E cases were 25.49%, 75.62 fl, 25.23 pg and 30.92 gm/dl respectively. It was also observed that the mean PCV, MCV, MCH, and MCHC were 18.5%, 65.14 fl, 21.29 pg and 30.97 gm/dl, respectively, in HbE/F cases. Anisocytosis, poikilocytosis, and target cells were present in almost all cases.

Serum ferritin level in HbE disorder [Table 4] and [Figure 2]
Figure 2: Graph showing the serum ferritin distribution


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Table 4: Serum ferritin distribution in HbE disorders


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It was observed from the present study that the serum ferritin level in case of HbA/E was lowest in contrast to HbE/E and HbE/F. The mean value of serum ferritin in HbA/E was 28.68 ng/ml. But mean value of serum ferritin in HbE/E and HbE/F were normal or high.

Serum ferritin value in HbE trait [Figure 3]
Figure 3: Pie diagram showing SF (ng/ml) in HbE trait cases


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It was observed that in cases of HbE trait serum ferritin value in case of males (20-45 ng/ml) was higher than females (22.07 ng/ml).

Serum ferritin levels in HbE disease [Figure 4]
Figure 4: Bar diagram showing mean SF level in HbE disease cases


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Cases with the history of intake of hematinics or transfused with blood showed serum ferritin values in the higher range (236.81 ng/ml and 189 ng/ml).

Serum ferritin level in HbE/F [Figure 5]
Figure 5: Bar diagram showing mean SF level in HbE-thalassaemia cases


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The mean serum ferritin value in HbE thalassaemia cases 1012.38 ng/ml. Those HbE-thalassaemia patients taking regular blood transfusions had higher serum ferritin values (1309.75 ng/ml) than those with occasional transfusions (715 ng/ml).


  Discussion Top


The prevalence of anemia is highly influenced by the presence of hemoglobinopathies in the regions where hemoglobinopathies are more frequent. Itano et al. (1954) first discovered HbE in a man of Guatemalan-Spanish-Hindi ancestry. HbE is a beta chain mutant hemoglobin in which glutamic acid B26 is substituted by lysine. [7]

The state of Assam, with its population showing diverse racial and linguistic groups, as well as many immigrant tribes from different states of India, is reported to be the rich reservoir of different hemoglobinopathy disorders. [4] Two most common abnormal hemoglobin disorders found in Assam are HbS and HbE. The frequency of sickling disorder ranges from 15 to 29% amongst the different tea garden labor populations in Assam. [8]

The age at the time of diagnosis of HbE/F varied from 1 month to 24 years. [9] The highest numbers of HbA/E patients are present in the age group of 20-30 years, and 30-40 years for HbE/E. [10] In the present study, most of the patients were in the age group of 11-30 years old (62.5%), the highest being in the age group of 21-30 years old (32.5%).

In the present study, the most common symptoms for HbA/E, HbE/E, and HbE/F patients were generalized weakness (67.5%). Patients with HbA/E remain without any clinical disability and anemia. [11] There may be the slight degree of anemia in HbA/E patients. [9],[12],[13] In view of the high rate of parasitism and the incidence of hepatic disturbance and iron deficiency among many of the inhabitants of Asia, it was not surprising to find a number of patients with HbA/E with abnormal hematological findings. [10] HbE state is not a disease entity but as a "tera in hematique fragile" on which malnutrition, parasitism, and thalassaemia lead to severe anemia. [14]

Hemoglobin percentage is ranging from 3.2 gm/dl to 16.5 gm/dl in HbE trait cases. [10] The mean P.C.V. in HbE trait cases are 43% and 37% respectively in male and female. [9] Microcytosis is also a feature in HbE trait cases. [10] The mean M.C.H and M.C.H.C in cases of HbE trait cases are respectively 26 pg and 33%. [9] The finding of low M.C.H.C in our study probably reflects the high incidence of iron deficiency anemia. Anisocytosis, poikilocytosis and target cells are present in most of the cases of HbE. [6],[15]

The hemoglobin level is 9.8 gm/dl in HbE disease cases. [9] It is ranging from 7.9 gm/dl to 13.2 gm/dl. [6] The mean is PCV is 31%. [9] This value is varied from to 37% to 41 ± 4%. [13],[15] Low PCV reflected probable presence of moderate to severe anemia in the group of patients in the present study. The M.C.V. value is in the range between 65 to 72 fl, [10] and MCH is 29.5 pg. [9] The M.C.H. value in HbE disease cases is in the range of 20 to 24 pg, [10] and MCHC is in the range from 29 to 34. [10] Anisocytosis and poikilocytosis and target cells are prominent in all HbE disease. [6],[15]

HbE thalassaemia is a condition of double heterozygous state. Age at time of diagnosis varies from one month to 24 years. [9] The hemoglobin level in HbE thalassaemia patients is in the range of 3 to 7 gm/dl. [10] The mean PCV is 20 ± 6 in HbE thalassaemia cases. [9],[10] The M.C.V. value is low between 65 and 75 fl. [10] The mean value of M.C.H. and M.C.H.C. are 21.29 (±2.84) pg and 27.7%. [9],[10] Anisocytosis, poikilocytosis, moderate hypochromia and presence of target cells are characteristics of HbE thalassaemia. [6],[9],[10],[15]

It was observed from the present study that the serum ferritin range of HbA/E is lowest in contrast to HbE/E and HbE/F. The mean value of serum ferritin in HbA/E was 28. 68 ng/ml with the range of 4 to 45 ng/ml. The mean value of serum ferritin in HbE/E and HbE/F was 175.29 ng/ml and 1012.38 ng/ml respectively. The range of serum ferritin in HbE/F was from 500-1500 ng/ml.

In cases of HbE trait serum, ferritin level in males is higher than females. Serum ferritin level in both sexes of HbE disease is within normal limit those do not receive the blood transfusion.

In the present study, 17.65% of HbA/E serum ferritin levels were ≤20 ng/ml and other 82.35% cases values were in the range of 21-100 ng/ml. Serum ferritin levels in 50% cases of HbE disease 151-399 ng/ml and 39.47% of cases in the range of 101-150 ng/ml. Only 4 cases of HbE/E ferritin level 21-100 ng/ml.

It was observed from the present study that mean serum ferritin values in both sexes in HbE disease were within normal limit (136.8 ± 11.62 in males, 93.5 ± 17.96 in females) in those who do not receive a blood transfusion. Cases with a history of intake of hematinics or blood transfusions showed serum ferritin values in a higher range (236.81 ng/ml and 189 ng/ml).

Saraya et al. found the mean serum ferritin values in untransfused thalassaemia major cases were lower (271.5 ± 244.2 ng/ml) than the transfused thalassaemia major cases (302.8 ± 162.6). [16]

One disastrous effect seen in severe beta thalassaemia (as well as in other causes of ineffective erythropoiesis) is excessive absorption of dietary iron coupled with the iron accumulation due to repeated blood transfusions required in these patients a severe state of iron overload develops. [16],[17]

It was observed in the present study that the mean serum ferritin value in HbE/F cases 1012.38 ng/ml, with ranges from 500 ng/ml to 1500 ng/ml. Those HbE/F patients taking regular blood transfusions had higher serum ferritin values (1309.75 ng/ml) than those with occasional transfusions (715 ng/ml).


  Conclusion Top


From the present study, it can be concluded that age at the presentation of symptoms in HbE disorders is mostly in the age group of 11 years to 30 years. Most of the cases were Ahom reflecting high prevalence among them. HbE disease and HbE thalassaemia are more symptomatic than HbE trait cases. The presence of incidental disorders makes the symptoms more severe. Splenomegaly is the feature in HbE/F (100%) and very common in HbE/E (84.2%) but is found less commonly in HbA/E (47%). Microcytosis is usual finding in HbE disorders. Serum ferritin assay IRMA technique is simple and suitable for evaluation of serum iron status. Iron deficiency may be present along with HbE and iron therapy is to be given if serum ferritin level is low. Serum ferritin level should be estimated routinely in all the cases of HbE presenting with anemia. Normal or higher serum ferritin in HbE disease and HbE thalassaemia cases in this study suggests that indiscriminate iron therapy could be harmful in most of the patients without prior evaluation of serum ferritin.

 
  References Top

1.
Weatherall DJ, Clegg JB. The Thalassemia Syndrome, 3 rd ed. Oxford: Blackwell Scientific Publication; 2001. p. 303.  Back to cited text no. 1
    
2.
Weatherall DJ, Clegg JB, Higgs DR, Wood WG. The hemoglobinopathies. In: Scriber CR, Beaudet AL, Sly WS, Vale D, Childs B, Kinzler KW, et al. editors. The metabolic and molecular basis of inherited disease. 8 th ed. New York: McGraw Hill; 2001;III. p. 4571-36.  Back to cited text no. 2
    
3.
Saha N. Distribution of haemoglobin E in several Mongoloid populations in northeast India. Hum Biol 1990;62:535-44.  Back to cited text no. 3
    
4.
Hundrieser J, Deka R, Gogoi BC, Papp T, Flatz G. DNA haplotypes and frameworks associated with the beta-globin gene in the Kachari population of Assam (India). Hum Hered 1988;38:240-5.  Back to cited text no. 4
    
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Das BM, Deka R, Das R. Hemoglobin E in six populations of Assam. J Indian Anthropol Soc 1980;15:153-156.  Back to cited text no. 5
    
6.
Flatz G, Chakravartti MR, Das BM, Delbrück H. Genetic survey in the population of Assam. I. ABO blood groups, glucose-6-phosphate dehydrogenase and haemoglobin type. Hum Hered 1972;22:323-30.  Back to cited text no. 6
    
7.
Itano HA, Bergren WR, Sturgeon P. Identification of the fourth abnormal hemoglobin. J Am Chem Soc 1954;76: 2278.  Back to cited text no. 7
    
8.
Batabyal JN, Wilson JM. Sickle cell anaemia in Assam. J Indian Med Assoc 1958;30:8-11.  Back to cited text no. 8
    
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Chatterjea JB. Some aspects of hemoglobin E and its genetic interaction with thalassemia. Ind J Med Res 1965;53:377-98.  Back to cited text no. 9
    
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Chernoff AI, Minnich V, Chongchareonsuk S. Hemoglobin E, a hereditary abnormality of human hemoglobin. Science 1954;120:605-6.  Back to cited text no. 10
    
11.
Dacie JV, Lewis SM. Investigations of Abnormal Hemoglobins and Thalassemias Practical Hematology. 10 th ed. Edinburg: Churchill Livingstone; 2006. p. 295.  Back to cited text no. 11
    
12.
Thomas F. Necheles, Donald M. Allen, Harvey E. Finkel. Clinical Disorders of Hemoglobin Structure and Synthesis with a foreword by Sydney S. Gellis, M.D. New York: Appleton-Century-Crofts, Education Division, Meredith Corporation (440 Park Avenue South, New York, New York 10016), 1969, 220.  Back to cited text no. 12
    
13.
Lachant N. Hemoglobin E: An emerging hemoglobinopathy in the United States. Am J Hematol 1987;25:449-62.   Back to cited text no. 13
    
14.
Brumpt L, Brumpt V, Coquelet ML, De Traverse PM. Detection of hemoglobin E in Cambodians. Rev Hematol 1958;13:21.  Back to cited text no. 14
    
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Swarup S, Ghosh SK, Chatterjea JB. Haemoglobin E disease in Bengalees.J Indian Med Ass 1960;35:13-5.  Back to cited text no. 15
    
16.
Saraya AK, Kumar R, Kailash S, Sehgal AK. Iron deficiency in beta-heterozygous thalassaemia. Indian J Med Res 1984;68-75.  Back to cited text no. 16
    
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Mehta BC, Agarwal MB, Varandani DG, Joshi RH, Bhargava AB. Hemoglobin E-thalassemia: A study of 16 cases. Acta Haematol 1980;64:201-4.  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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