|Year : 2022 | Volume
| Issue : 4 | Page : 490-495
A study of spectrum of sickle cell anemia and thalassemia in a teaching institute of South India
SS Sabitha Rani1, IS Vamshidhar2, S Bangaru3, NA John2, J John4
1 Department of Pathology, ESIC Medical College and Hospital, Sanathnagar, Hyderabad, Telangana, India
2 Department of Physiology, All India Institute of Medical Sciences (AIIMS), Bibinagar, Telangana, India
3 Department of Pathology, Government Medical College and Hospital, Nalgonda, Telangana, India
4 Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Nagpur, Maharashtra, India
|Date of Submission||16-Aug-2021|
|Date of Acceptance||06-Dec-2021|
|Date of Web Publication||19-Apr-2022|
Dr. I S Vamshidhar
Postal Address: H. No: 30-2-701/A, West City, Kazipet, Madikonda, Warangal Urban - 506 142, Telangana
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background and Aim: Sickle cell syndrome is a group of inherited hematological disorders with varying degrees of anemia, jaundice, fatiguability along with hepatomegaly and splenomegaly. The clinical presentations can be may vary and therefore require thorough investigations. We tried to evaluate the spectrum of sickle cell anemia and thalassemia in pediatric patients of our hospital. Patients and Methods: In this cross-sectional study, A total of n = 200 consecutive cases were detected during the period of study. A thorough history and detailed clinical examination were done. Hb electrophoresis was done in the present study using HYDRASYS ® Electrophoresis Systems from Sebia. Results: The overall prevalence of SCD in our study was 6.83% the existence of this is found to be greater in the males as compared to females which is in agreement with prevalence across India with more male than female. Thalassemia was prevalent at the rate of 3.96%, sickle cell anemia had a prevalence of 1.98% sickle thalassemia was 0.89%. N = 20 pairs of Parents recognized genetic counseling i.e., with a single child or who wanted further children readily underwent HPLC analysis. Conclusion: The existence of SCD in our study group is lesser as compared to the South India average. Preventive programs consisting of public education, population screening, genetic counseling, and prenatal diagnosis have been very effective in reducing both rates of β-Thalassemia major. Sickle cell anemia is of prime importance because of its high prevalence, morbimortality and the absence of curative treatments.
Keywords: Hemoglobinopathies, sickle cell anemia, sickle cell thalassemia, thalassemia
|How to cite this article:|
Sabitha Rani S S, Vamshidhar I S, Bangaru S, John N A, John J. A study of spectrum of sickle cell anemia and thalassemia in a teaching institute of South India. Niger J Clin Pract 2022;25:490-5
|How to cite this URL:|
Sabitha Rani S S, Vamshidhar I S, Bangaru S, John N A, John J. A study of spectrum of sickle cell anemia and thalassemia in a teaching institute of South India. Niger J Clin Pract [serial online] 2022 [cited 2022 May 18];25:490-5. Available from: https://www.njcponline.com/text.asp?2022/25/4/490/343457
| Introduction|| |
Sickle cell anemia is an inherited disorder an autosomal recessive inheritance that is characterized by sickle-shaped red blood cells (crescent shape). It is the most common type of hemoglobinopathy and is the result of a mutation in the β-globin chain gene that results in creating sickle hemoglobin (HbS) instead of the normal adult hemoglobin (HbA). Sickle cell disease is a term used in a generic sense to identify all of the sickling syndromes and include sickle cell anemia and Thalassemia. Herrick first described sickle cell in 1910. It was proven by Ingram et al., that sickle cell disease was caused due by a mutation (Glutamine → Valine) substituted at the 6th globin polypeptide. Sickle cell disease because of its prevalence and worldwide distribution, the disorders resulting from sickle Hb (HbS) are of enormous clinical importance. The genetic basis of sickle cell disease and each major hemoglobinopathy occurs in both a heterozygous and a homozygous form. In the heterozygous state, red cells contain both normal adult Hb (HbA) and the variant Hb. It is a recessive gene consequently heterozygotes are carriers and in such cases about half of the HbA will be replaced by HbS whereas, homozygotes have exclusively HbS. In a homozygous state, HbA is completely absent, and clinical manifestations of variable severity, individuals so affected have sickle cell anemia. Apart from these, the disease also results from a combination of two variants of hemoglobin or a variant Hb and an interacting thalassemia gene. The double heterozygous states are named as Hb SC disease, Hb S/β-Thalassemia based on the presence of both aberrant gene products.
As per WHO, 4.5 to 5% of the world's population are carriers of hemoglobinopathies. In India, 30 million carriers and a mean prevalence is 3.3%., The incidence of sickle cell anemia in India varies between 1 to 44% and beta-thalassemia trait ranges from 3 – 17% the possible cause could be because of a higher rate of consanguinity., The sickle cell trait is particularly higher in Maher, Pradhan, Kurmi, Panka, and Otkar communities where it is >20%. The Higher incidence of sickle cell anemia is particularly found in the tribal population of central and South India. The prevalence of thalassemia is more common in Parsee, Sindhi, Lohana, Punjabi and Gujarati communities of India.,,, Hemoglobin S; is so-called because of the sickle shape it imparts to deoxygenated red cells, is responsible for a wide spectrum of disorders with high variability in the degree of anemia, frequency of crisis, extent of organ injury and duration of survival. Some of the sickling syndromes lack significant pathologic potential, but they are easily confused with clinically aggressive disorders based on laboratory evaluation, consequently precision in diagnosis is essential both to proper clinical management and to meaningful genetic counseling.
| Material and Methods|| |
Institutional Ethical permission was obtained for the study after following the due protocol for human research. The study was conducted on patients between the age groups of 1-month-old to 60 months old presenting with anemia and those who presented with other complaints but were incidentally found to have anemia.
- Consecutive samples of children under 5 years admitted to the Department of Pediatrics with anemia.
- Children with anemia attending the outpatient department.
A total of n = 200 consecutive cases were detected during the period of study. A thorough history and detailed clinical examination were done for each patient and the data was recorded in the standard case record form. The venous blood sample was collected in vacutainers and the samples were analyzed using an Autoanalyzer (Sysmex KX-21) Hematology Analyzer, Japan. The Complete hemogram with RBC indices and Reticulocyte count was done. Peripheral smears were prepared on glass slides and stained with Leishman's stain. The reticulocyte count was done by the supravital staining technique using Brilliant cresyl blue. The hemolytic anemia cases, which were suspected on clinical and peripheral blood examination, were taken up for a complete hematological workup including Hb electrophoresis, osmotic fragility, and Coomb's test depending on the specific requirement. Other ancillary tests including urine examination, liver function tests, radiological investigations like chest x-ray, skeletal survey, ultrasonography and CT scan were done whenever required. Hb electrophoresis was done in the present study using HYDRASYS ® Electrophoresis Systems from Sebia. which is a multiparameter semi-automated instrument in which hydrogel agarose gels are used. It is based on the principle that Hb when placed in an electric field, migrates towards one of the electrodes. Alkaline Hb electrophoresis on an agarose gel was used as a screening procedure for Hb A, F, S and C and further differentiation was done using a gel with an acidic pH. HbA2: 4-5.8% (β-thalassemia minor) and Under 2% (Hb H disease). HbF: 2-5% (β-thalassemia minor), 10-90% (β-thalassemia major), 5-35% (Heterozygous hereditary persistence of fetal hemoglobin or HPFH) 100% (Homozygous HPFH), 15% (Homozygous Hb S). Homozygous HbS: 70-98% (Sickle cell disease).
The blood sample of the patient is collected in an EDTA tube and a few drops are added to a glass slide. This blood sample on the slide is mixed with sodium Meta bisulfate and stored in anaerobic conditions for 30 min followed on by transferring the contents to a new glass slide. These contents are covered by a Vaseline strip and by the oil immersion method, the sickle cells are seen.
The obtained data were entered and analyzed using Windostat 9.2 Software. Percentage, proportions and contingency tables were used for the description of the data. The clinical and the laboratory profile of the various anemias reported were analyzed. A P value less than 0.05 was considered significant.
| Results|| |
T total of 200 inpatient children with Sickle cell anemia and Sickle thalassemia trait from age 1 – 60 months were taken up for the present study. The total number of admissions in the pediatric medical ward during the study period is n = 10,232 (excluding neonates). Under 5 years age group pediatric admissions (excluding neonates) during the study period was n = 2928 of which n = 200 were suffering from Thalassemia, Sickle cell anemia and sickle cell trait. The mean age of boys was 29.8 ± 15.6 months, mean age of the girls was 24.5 ± 15.04 months [Table 1]. Ninety-five (47.5%) were in upper-lower, 60 (30%) in lower-middle, 35 (17.5%) were in lower, 10 (5%) were in upper-middle-class as per modified Kuppuswamy scale. 83% of the entire sample were from rural areas and 17% of the from the urban areas.
Of all the patients in the study sample, only n = 23 (12.5%) of the sample reported had fatigue as the chief complaint. Though the activity levels were decreased significantly during hospitalization, only 7 (3.5%) of the parents of these children complained of tiredness. The frequency of the patients reporting various chief complaints was 20% fever, 7% cough, 6% cold, 3% vomiting, 3% loose bowel motions, 4% abdominal distention, 2% anorexia, 2% joint pains and 7% jaundice. The cases of consanguinity were found in 68.1%, 82.7% and 69.2% of thalassemia, sickle cell anemia and sickle thalassemia respectively.
Positive history in Thalassemia, sickle cell anemia, and sickle thalassemia was significantly more. 116 siblings siblings with thalassemia, sickle cell anemia and sickle thalassemia were investigated with HPLC, n = 36 (31.1%) of were traits with no clinical disease or had normal HPLC. The number of patients who underwent transfusions were 87% in Beta-Thalassemia and 71% in sickle cell anemia and this was found to be statistically significant [Graph 1]. Hepatosplenomegaly was found in 67 (57.7%), Hepatomegaly in (15; 12.9%) and Splenomegaly (24; 20.6%) in Thalassemia Patients. Thalassemia major was commonly diagnosed in cases below 2 years of age. Sickle cell anemia and Sickle Thalassemia were diagnosed mostly between 3 – 5 years of age as depicted in [Table 2].
In this study we were able to diagnose Beta-thalassemia major in n = 85 (42.5%) cases, beta-thalassemia minor in n = 34 (17%) cases. The sickle cell anemia was found in n = 46 (23%), sickle cell trait was present in n = 17 (8.5%) and sickle cell thalassemia was in n = 18 (9%) of cases. The study of hemoglobin, RBC count, reticulocyte count and red cell morphology was done in all the cases, the results are depicted in [Table 3].
|Table 3: Mean hemoglobin, RBC Count, HCT, MCV, MCH, MCHC, RDW and reticulocyte count|
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The study included n = 200 inpatient children of pediatric wards. In the cases diagnosed with Hemoglobinopathies, parents were offered to undergo screening with Hb Electrophoresis. However, majority of parents refused to get investigated. N = 20 pairs of parents underwent HPLC investigations the results have been depicted in [Table 4].
|Table 4: Hb Electrophoresis results of the parents of the cases included in the study|
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| Discussion|| |
Sickle cell hemoglobinopathies are a group of disorders that includes SCA, SCT and sickle/beta-thalassemia. Sickle cell anemia (SCA) and sickle cell trait (SCT) are the familiar forms of Hb defect (HbS gene) that are inherited by children from their parents., The sickle cell gene was first found in the Nilgiri Hills of north Tamil Nadu in the year 1952., It has now been found to be widespread among the people of the Deccan plateau of central India with small foci in North Kerala and Tamil Nadu., Since the gene frequency is high in our region of Telangana, we focused on the study of sickle cell hemoglobinopathies at our Tertiary care Institute at MGM Warangal with special emphasis on the clinico-hematological profile of patients. In the current study, a significant association was found between the age of the infant and the occurrence of sickle cell anemia. Thalassemia major was commonly diagnosed in cases below 2 years of age. The detection of Thalassemia major at early age is due to severe impairment of formation of hemoglobin which manifests earlier as compared to other form of hemoglobinopathies. Sickle cell anemia and sickle thalassemia were diagnosed mostly between 3 – 5 years of age. Akodu et al.,, in Nigeria found Children older than six months were at a higher risk of sickle cell anemia. The infants below 6 months would not show clinical signs because of HbF predominance. The higher levels of HbF tend to inhibit sickling. The overall prevalence of SCD in our study was 6.83% the existence of this is found to be greater in males as compared to females which is consistent with the prevalence of the disease across India. Thalassemia was prevalent at the rate of 3.96%, sickle cell anemia had a prevalence of 1.98% sickle thalassemia was 0.89%. Some earlier studies done across India have reported prevalence for sickle cell genes in tribal populations to range from 0 –37.79%.,,, The Indian Council of Medical Research ICMR in the year 2000 extensive multicenter study under the 'Jai Vigyan' project to create awareness in the population and to determine the prevalence of beta-thalassemia and other hemoglobinopathies in six States from different regions of the country. Subsequently the National Rural Health Mission (NRHM) of Government of India implemented Cost effective population screening programs for detection of carriers, as low-cost screening tests with high negative predictive value are available for detection of carriers of β-thalassemia (also referred to as β Thalassemia Trait (BTT)), HbS Carriers (HbS Trait) and HbE carriers (HbE Trait) in accordance with WHO report on services for prevention and management of genetic disorders in developing countries. However, Genetic counseling, community education and awareness plays a very important role in successful implementation of prevention programs. Services and screening programs were sensitive to cultural and social practices and religious beliefs. In many rural areas with lower education and strong cultural beliefs act as impediments. Our results show decrease awareness among parents and only few agreed for HPLC investigations as depicted in [Table 4]. The values of HbA2 were found in this study to be significantly elevated and HbF mildly elevated in those with thalassemia minor, whereas the reverse was with thalassemia major where HbF was significantly elevated and HbA2 shows marginal elevation [Table 5]. The increase in hemoglobin A2 is considered a significant parameter in the identification of beta-thalassemia carriers.,
In this study, we found beta-thalassemia major in 42.5% of cases and a beta-thalassemia minor in 17% of cases. Abdul Karim et al., in their study also found the prevalence of beta-thalassemia major greater than beta-thalassemia intermedia and least was beta-thalassemia minor.
In this study, the clinical signs and symptoms expressed by the patients diagnosed with Thalassemia revealed gastrointestinal tract disturbances were common. It appears that in cases of thalassemia there is an increase in extramedullary hematopoiesis affecting the liver and spleen therefore such patients report with gastrointestinal problems commonly. A comparison between the laboratory findings and symptoms presented between sickle cell anemia and sickle thalassemia, MCV and MCH levels were found to be low in sickle thalassemia but HbA2 levels were found to be increased as also seen in a study by Zago et al.,
In this study, the clinical signs and symptoms expressed by the patients diagnosed with Thalassemia revealed gastrointestinal tract disturbances were common. A comparison between the clinical signs and symptoms presented between sickle cell anemia and sickle thalassemia, MCV and MCH levels were found to be low in sickle thalassemia but HbA2 levels were found to be increased as also seen in a study by Zago et al.,
| Conclusion|| |
The hemoglobinopathies constitute a significant health care burden in developing countries with lesser resources. The existence of SCD in our study group is lesser as compared to the South India average. Preventive programs consisting of public education, population screening, genetic counseling and prenatal diagnosis have been very effective in reducing both rates of β-Thalassemia major. Sickle Cell Disease is of prime importance because of its high prevalence, morbimortality and the absence of curative treatments. Thus, a detailed analysis was necessary to not only reduce the incidence of Sickle Cell Disease in this group of the population but also highlight the prevalence, importance of understanding the genetic basis of the hemoglobinopathies.
The authors thank the Dept of Pathology, and Pediatrics, Mahatma Gandhi Memorial Hospital, Kakatiya Medical College, Warangal, Telangana State, India, for their support in the conduction of this study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ballas SK, Lieff S, Benjamin LJ, Dampier CD, Heeney MM, Hoppe C, et al
. Definitions of the phenotypic manifestations of sickle cell disease. Am J Hematol 2010;85:6-13.
Forget BG, Bunn HF. Classification of the disorders of hemoglobin. Cold Spring Harb Perspect Med 2013;3:a011684. doi: 10.1101/cshperspect.a011684.
Balgir RS. The burden of hemoglobinopathies in India and the challenges ahead. Curr Sci 2000;79:1536-47.
Ingram VM. Gene mutations in human haemoglobin: The chemical difference between normal and sickle cell haemoglobin. Nature 1957;180:326-8.
Julia Zhe Xu, Swee LT. The carrier state for sickle cell disease is not completely harmless. Haematologica 2019;104:1106-11.
Thein SL. The molecular basis of β-thalassemia. Cold Spring Harb Perspect Med 2013;3:a011700. doi: 10.1101/cshperspect.a011700.
Verma IC, Choudhry VP, Jain PK. Prevention of thalassemia: A necessity in India. Indian J Pediatr 1992;59:649-54.
Balgir RS. The genetic burden of hemoglobinopathies with special reference to community health in India and the challenges ahead. Indian J Hematol Blood Transfus 2002;20:2-7.
Ashley Koch A, Yang Q, Olney RS. Sickle hemoglobin (HbS) allele and sickle cell disease: A HuGE review Am J Epidemiol 2000;151:839-45.
Saha N, Banerjee B. Incidence of abnormal hemoglobins in Punjab. Calcutta Medi J 1965;62:82-6.
Balgir RS. Genetic epidemiology of the three predominant abnormal hemoglobins in India. J Assoc Physicians India 1966;44:25-8.
Jawahirani A, Mamtani M, Das KK, Rughwani V, Kulkarni H. Prevalence of beta-thalassemia in subcastes of Indian Sindhi: Results from a two-phase survey. Public Health 2007;121:193-8.
Frank F, Coli C, David P, Brayan R. De Gruchy's Clinical Haematology in Medical Practice. 5th
ed. Oxford Scientific; 1989. p. 133.
Kumar N, Shekhar C, Kumar P, Kundu AS. Kuppuswamy's socioeconomic status scale- Updating for 2007. Indian J Pediatr 2007;74:1131-2.
Lehman H, Cutbush M. Sickle cell trait in southern India. Br Med J 1952;1:404-5.
Colah R, Mukherjee M, Ghosh K. Sickle cell disease in India. Curr Opin Hematol 2014;21:215-23.
Akodu SO, Diaku-Akinwumi IN, Njokanma OF. Age at diagnosis of sickle cell anaemia in Lagos, Nigeria. Mediterr J Hematol Infect Dis 2013;5:e2013001.
Naidu JM, Mohrenwiser HW, Nee JV. A serobiochemical genetic study of Jalari and Brahmin caste populations of Andhra Pradesh, India. Human Hered 1985;35:148-56.
Banerjee S, Roy M, Dey B, Mukherjee BN, Bhattacharya SK. Genetic polymorphism of red cell antigen, enzyme, haemoglobin and serum protein in 15 endogamous populations of South India J Indian Anthrop Soc 1988;23:250-9.
Colah RB, Mukherjee MB, Martin S, Ghosh K. Sickle cell disease in tribal populations in India. Indian J Med Res. 2015 May;141:509-15.
Rao VR. Genetics and epidemiology of sickle cell anemia in India. Indian J Med Sci 1988;42:218-22.
Blake NM, Ramesh A, Vijayakumar M, Murty JS, Bhatia KK. Genetic studies on some tribes of the Telangana region, Andhra Pradesh, India. Acta Anthropogenet 1981;5:41-56.
Abdul-Karim ET, Abdul Jalil FH, Al Azawi TN. Study of different clinical and demographic characters of patients with thalassemia and their relation to hemoglobin, some minerals and trace elements, and albumin levels in their blood. Iraq J Med Sci 2005;4:21-37.
Zago MA, Costa FF, Freitas TC, Bottura C. Clinical, hematological, and genetic features of sickle-cell anemia and sickle cell-beta thalassemia in a Brazilian population. Clin Genet 1980;18:58-64.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]