|Year : 2020 | Volume
| Issue : 4 | Page : 342-345
Clinico-hematological parameters of sickle hemoglobin hemoglobinopathies and its correlation with ethnicity: A study from Northern Districts of West Bengal
Bidyut Krishna Goswami1, Rajashri Chakrabarty2, Subrata Bhattacharjee1, Ankita Dhanuka1, Sarama Banerjee Goswami3, Sudipta Chakrabarti4
1 Department of Pathology, North Bengal Medical College, Darjeeling, India
2 Department of Pathology, Coochbehar Government Medical College and Hospital, Coochbehar, India
3 Critical Care Unit, North Bengal Medical College and Hospital, Darjeeling, India
4 Department of Pathology, ESI PGIMSR Manicktala, Kolkata, West Bengal, India
|Date of Submission||30-Aug-2020|
|Date of Acceptance||26-Sep-2020|
|Date of Web Publication||30-Dec-2020|
Prof. Sudipta Chakrabarti
Department of Pathology, ESI PGIMSR, Manicktala, 54 Bagmari Road, Kolkata - 700 054, West Bengal
Source of Support: None, Conflict of Interest: None
Background: Inherited disorders of blood include thalassemias and hemoglobinopathies which are one of the major public problems in India. In sickle hemoglobin (HbS) hemoglobinopathies, production of abnormal sickle-shaped red cells results in variable degree of hemolytic anemia along with acute and chronic tissue damage due to vaso-occlusion. The term sickle cell anemia is reserved for homozygous state (SS) for sickle cell gene, while the heterozygous sickle cell trait (AS) has never been considered a disease, has one abnormal gene. Aims: The present study was undertaken to determine the occurrence of HbS hemoglobinopathies in Northern districts of West Bengal and its correlation with ethnicity and different hematological parameters. Methods: A hospital based cross-sectional study was carried out in the Department of Pathology, North Bengal Medical College , along with its thalassemia control unit, over a period of 5 years. Various hematological parameters (Hb, packed cell volume, mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], MCH concentration [MCHC], red cell distribution width) were calculated, and hemoglobin variants were determined by high-performance liquid chromatography. Results: 908 (2.19%) patients of sickle cell disease SCD were diagnosed, among a total of 41,549 cases studied. The distribution of HbS hemoglobinopathies were SS-51 (5.6%), AS-727 (80.1%), HbS/beta thalassaemia-109 (12.0%), compound heterozygisity for HbS/Hb E hemoglobinopathy 10 (1.1%) cases. The study revealed that 769 (84.7%) of such HbS variants occurred among the tribal population. Low values of MCV, MCH, and MCHC were noted in both sickle cell trait and in HbS/beta-thalassemia. Conclusion: There is a high occurrence of sickle cell disease in the socioeconomically backward population groups. Mass screening is required in this region for the assessment of different hemoglobin variants among the diverse ethical groups.
Keywords: Ethnicity hematological parameters, northern districts of West Bengal, sickle hemoglobin hemoglobinopathies
|How to cite this article:|
Goswami BK, Chakrabarty R, Bhattacharjee S, Dhanuka A, Goswami SB, Chakrabarti S. Clinico-hematological parameters of sickle hemoglobin hemoglobinopathies and its correlation with ethnicity: A study from Northern Districts of West Bengal. Biomed Biotechnol Res J 2020;4:342-5
|How to cite this URL:|
Goswami BK, Chakrabarty R, Bhattacharjee S, Dhanuka A, Goswami SB, Chakrabarti S. Clinico-hematological parameters of sickle hemoglobin hemoglobinopathies and its correlation with ethnicity: A study from Northern Districts of West Bengal. Biomed Biotechnol Res J [serial online] 2020 [cited 2022 Jan 25];4:342-5. Available from: https://www.bmbtrj.org/text.asp?2020/4/4/342/305637
| Introduction|| |
Worldwide, the most common abnormal hemoglobin variant is sickle hemoglobin (HbS), and its global distribution among indigenous populations exposed to malaria may reach in high frequencies because of the resistance impart against malaria in the carriers.
In sickle cell hemoglobinopathy, there is the production of abnormal sickled-shaped red cells with variable degree of hemolytic anemia, acute and chronic tissue damage due to vaso-occlusion. The term sickle cell anemia is reserved for homozygous state for sickle cell gene, while sickle cell trait has one abnormal gene. The molecular basis for sickle cell disease is an A to T transversion in the 6th codon of the human β-globin gene. While the carrier leads a normal life, the diseased persons suffer from various complications such as anemia, frequent infections, etc., The occurrence of sickle cell hemoglobinopathy among the different tribal group in India varies between 1% and 40%. The occurrence of HbS is about 20% in Madhya Pradesh, Chhattisgarh, Odisha, Gujarat, and Maharashtra., Only results of a few centers for screening of abnormal variant of hemoglobin is available., A comprehensive screening from Northern districts of West Bengal has reported beta-thalassemia and Hb-E hemoglobinopathies are more commonly observed. The present study was undertaken to determine the occurrence of sickle cell hemoglobinopathies from the northern districts of West Bengal, its correlation with ethnicity, and observed hematological parameters. The study had also investigated the ethnic correlation of SCD as in other cases of hemoglobinopathies.
| Materials and Methods|| |
A hospital based cross-sectional study was carried out in the Department of Pathology, North Bengal Medical College and Hospital along with its Thalassemia Control Unit (TCU), over a period of 5 years. Cases of pallor or weakness who had attended the TCU for screening and from the camps arranged by TCU were selected for this study. Persons who had a history of transfusion in immediate past 3 months were excluded from the study After obtaining the clinical history, clinical examination, including examination of hematopoietic systems, was performed. Laboratory investigations, including complete blood count (CBC), peripheral blood smear study, and reticulocyte count, were undertaken. Blood sample for CBC was collected in vials containing disodium salt of ethylenediaminetetraacetic acid as anticoagulant and performed by using automated cell counter (Sysmax K × 21E-210, Japan). Peripheral smear study and reticulocyte count was also performed. Hemoglobin variant was evaluated by cation-exchange high-performance liquid chromatography principle, using Variant 2 (Bio-Rad, USA) automated (capillary electrophoresis high-performance liquid chromatography [HPLC]). For further determination of abnormal hemoglobin variant, hemoglobin electrophoresis and sickling test were also performed for correlation. All the tests were done under proper quality control measures. Double heterozygous state and homozygous state were corroborated with family screening.
| Results|| |
A total of 908 cases were diagnosed as having sickle cell hemoglobinopathies among 41,549 cases (2.19%) studied. The condition was detected more commonly in females (488 cases, 53.8%) than males (420 cases, 46.2%). Male-to-female ratio was 1:1.16. The condition was most commonly identified in the age group of 11–30 years [Table 1]. The disease was found predominantly in the aboriginal population, particularly in the schedule (Oraon, Murmu, Munda). Tribes, (769 cases, 84.7%) cases [Table 2]. The Muslim population consisted of 8.4% (76 cases) of total cases. Women were more anemic (average Hb 9.47 gm/dl) compared to males (10.63 gm/dl). Among the total 908 cases, HPLC chromatogram revealed 727 (80.1%) persons were of sickle cell trait, and HbS disease was noted in 51 (5.6%) cases [Figure 1]. 109 (12.0%) cases were of HbS/beta thalassemia, while 10 (1.1%) cases showed compound heterozygosity for HbS/Hb E hemoglobinopathy. In 11 (1.2%) persons, HbS hemoglobinopathy with raised HbF which could not be further classified.
|Table 1: Distribution of age group of sickle haemoglobin hemoglobinopathis showing most common age groups are 11- 20 and 21- 30 years|
Click here to view
|Table 2: Distribution of population group of sickle haemoglobin hemoglobinopathis showing most common occurrence was among various tribes|
Click here to view
|Figure 1: High performance liquid chromatography chromatogram of sckle cell disease (above) and sickle cell trait (below)|
Click here to view
Observation of red blood cell parameters in different variant of hemoglobin is given in [Table 3]. Cases having sickle cell disease had an average low hemoglobin of 6.33 g/dl in contrast to sickle cell trait persons (10.82 g/dl) while Hbs/beta thalassemia heterozygous persons had mean hemoglobin of 7.17 g/dl. Mean corpuscular volume (MCV) was low in cases of sickle cell trait and Hbs/beta-thalassemia in contrast to persons with sickle cell disease. The average amount of HbS was 76.6 in cases of HbS disease, whereas in Hbs/beta-thalassemia (Hb S/β-Thal) the mean value of HbS was 70.1% [Table 4].
|Table 3: In cases sickle cell trait and sickle haemoglobin/beta thalassaemia, mean corpuscular volume was low of in contrast to persons with sickle cell disease|
Click here to view
|Table 4: The quantification of haemoglobin variant among different categories of sickle haemoglobin hemoglobinopathies|
Click here to view
| Discussion|| |
The sickle cell hemoglobinopathy is the most common single-gene disorder of which 50% of the world population resides in India. The sickle cell hemoglobinopathies is the most common single-gene disorder. The WHO (2006) has reported an estimate of about 20–25 million individuals for Hb-S diseases, of which 5–10 million are in India.
In India, 73% sickle gene has been reported in tribal people in various studies. In our study, we have observed that sickle cell Hemoglobinopathies in 2.19% of the population screened and we also observed 84.7% of the patients belong to the scheduled tribe community, mostly Lohar, Baraik, Chikbaraik, Kachua., who are coming from different trustees of Tea-gardens, found in this zone. These tribals are actually migrated from Tribal areas of Chhotonagpur (now in Jharkhand). As a result of geographical and social barriers, lack of primary and specialty care health facilities, burgeoning birth rate, and consanguineous marriage practices, there is a dangerously high prevalence of genetic disorders among tribal populations. It is the presence of sickle cell anemia among tribal populations that has surged to the forefront as a critical public health problem among tribal groups. Muslims consisted of 8.4% of total cases and is lower in comparison to other studies,, which is in contrast to the high occurrence of HbE-Beta Thalassemia in the Muslim population of this zone. The occurrence of HbS Hemoglobinopathies as a whole is slightly higher in females in our study, which differs from the study by Pathak et al. and Shrikhande et al. where males outnumbered females. The mean hemoglobin is low in patients suffering from homozygous state as well as in double heterozygous state with beta-thalassemia is due to the severity of the chronic hemolytic process and frequent complications. Mean hemoglobin is also low in female patients may be attributable to the burden of multiple pregnancies and nutritional deficiencies. Distribution of MCV was on the higher side of the normal range in patients with HbS Disease maximum being 121 fl. The observation can be explained by the increase in demand due to increase need for erythropoiesis because of chronic hemolysis or hematuria or pregnancy can precipitate deficiency state leading to macrocytosis, supporting others observations. Red cell distribution width is also raised in all subgroups of HbS Hemoglobinopathies, except in Hb-S carriers, as according to most of the literature HbS carriers are considered to normal or near-normal in all senses., Average HbA2 level in sickle cell disease in the present study (1.63 ± 0.30) is slightly lower than other studies done by Kar et al. (1.89 ± 0.52%) and Shrikhande et al. (2.09(±0.93). MCV, mean corpuscular hemoglobin (MCH) and MCH concentration (MCHC) were low in both sickle cell trait and in HbS/beta thalassemia. In cases of HbS/beta thalassemia, this is well explained. However in some cases of sickle cell disease and trait, this unusual low MCV, MCH, and MCHC may be related to concomitant Iron Deficiency, which is in need of investigations to rule out nutrition deficiencies and the possibility of concomitant alpha thalassemias (As also suspected in cases of HbE hemoglobinopathies, highly prevalent in this zone). Symptomatic HbS Hemoglobinopathies (sickle cell disease, HbS/beta-thalassemia, etc.) are less dependent on regular blood transfusion, which may be related to high mean HbF. Average HbF is significantly higher in our study, particularly in homozygous patients (19.19%), which was similar to the observation by Shrikhande et al. but differs with the study by Hayes et al. and Kar et al. In many asymptomatic cases, significant rise in HbF was noted, though parental screening were not supportive to conclude this group of the patient as HbS/beta thalassemia. Mutation analysis of such cases is necessary for appropriate categorization.
| Conclusion|| |
The present study highlights the substantial occurrence of various categories of HbS Hemoglobinopathies in northern districts of West Bengal, which has a known high prevalence for HbE hemoglobinopathy and beta thalassemia. The HbS variants are found to be mostly confined to some groups of scheduled tribes of the poor socio-economic group, mostly residing at tea-garden bustees. There are noteworthy occurrences of double heterozygous states with beta-thalassemia and even with HbE Hemoglobinopathies, consequently having varying hematological presentations. The existence of genetic modifiers, including co-inheritance alpha thalassemia and quantitative trait loci affecting the production of HbF, cannot be ruled out. These findings indicate a need of vigorous mass screening by hematological investigations and mutation analysis for variant hemoglobin.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Piel FB, Patil AP, Howes RE, Nyangiri OA, Gething PW, Williams TN, et al
. Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis. Nat Commun 2010;1:104.
Mahesh KS, Aggarwal SU, Bhasker A, Vijaya M, Mukhopadhyay R, Saraswathy KN. Distribution pattern of HbS and β-globin gene haplotypes among koya dora tribe of Andhra Pradesh. Int J Hum Genet 2011;11:123-6.
Konotey-Ahulu FI. The sickle cell diseases: Clinical manifestations including the sickle crisis. Arch Int Med 1974;133:611.
Steinberg MH. Sickle cell anemia, the first molecular disease: Overview of molecular etiology, pathophysiology, and therapeutic approaches. Sci World J 2008;8:1295-324.
Sorette MP, Lavenant MG, Clark MR. Ektacytometric measurement of sickle cell deformability as a continuous function of oxygen tension. Blood 1987;69:316-23.
Colah RB, Mukherjee MB, Martin S, Ghosh K. Sickle cell disease in tribal populations in India. Indian J Med Res 2015;141:509-15.
] [Full text]
Flint J, Harding RM, Boyce AJ, Clegg JB. The population genetics of haemoglobinopathies. Baillieres Clin Haematol 1998;11:1-50.
Dolai TK, Dutta S, Bhattacharyya M, Ghosh MK. Prevalence of hemoglobinopathies in rural Bengal, India. Hemoglobin 2012;36:57-63.
Bhattacharyya KK, Chatterjee T, Mondal UB. A comprehensive screening program for β-thalassemia and other hemoglobinopathies in the Hooghly District of West Bengal, India, dealing with 21137 cases. Hemoglobin 2016;40:396-9.
Goswami BK, Pramanik R, Chakrabarty S, Pal PP, Banerjee S, Bandyopadhyay A. Spectrum of hemoglobin variants in the population of northern region of west bengal: An ethnogenetic proposition. J Family Med Prim Care 2014;3:219-23.
] [Full text]
Bain BJ. Sickle cell haemoglobin and its interactions with other variant haemoglobins and with Thalassaemias. In: Bain BJ, editors. Hemoglobinopathy Diagnosis. 2nd
ed. Oxford: Blackwell Publishing Ltd; 2006. p. 139-88.
Ghai OP. Essential Paediatrics. 5th
ed. New Delhi: Interprint; 2000. p. 100.
Rao VR. Variation of HbS frequency in Indian population role of P. Falciparum and other factors. Indian J Hum Genet 1998;4: 23-31. [Full text]
Balgir RS. Scenario of haemoglobin variants in Central-East coast of India. Curr Sci 2006;90:1651-7.
Sinha S, Kumar A, Gupta V, Kumar S, Singh VP, Raman R. Haemoglobinopathies-thalassemias and abnormal haemoglobins in eastern Uttar Pradesh and adjoining districts of neighboring states. Curr Sci 2004;87:775-80.
Pathak K, Kishore S, Anshu , Shivkumar VB, Gangane N, Sharma S. Study of haemoglobin S percentage and haematological parameters in sickle cell trait. Indian J Pathol Microbiol 2003;46:420-4.
Shrikhande AV, Dani AA, Tijare JR, Agrawal AK. Hematological profile of sickle cell disease in central India. Indian J Hematol Blood Transfus 2007;23:92-8.
Wong YW, Elliott-Mills D, Powars D. Renal failure in sickle cell anaemia. Haematol Oncol Clin N Am 1996;10:1321-31.
Sklar AH, Campbell H, Caruana RJ, Lightfoot BO, Gaier JG, Milner P. A population study of renal function in sickle cell anemia. Int J Artif Organs 1990;13:231-6.
Hayes RJ, Beckford M, Grandison Y, Mason K, Serjeant BE, Serjeant GR. The haematology of steady state homozygous sickle cell disease: Frequency distributions, variation with age and sex, longitudinal observations. Br J Haematol 1985;59:369-82.
Forget BG, Bunn HF. Classification of the disorders of hemoglobin. Cold Spring Harb Perspect Med 2013;3:a011684.
Kar BC, Satapathy RK, Kulozik AE, Kulozik M, Sirr S, Serjeant BE, et al
. Sickle cell disease in Orissa State, India. Lancet 1986;2:1198-201.
[Table 1], [Table 2], [Table 3], [Table 4]