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Prevalence and spectrum of haemoglobinopathies in females of reproductive age group- A first tertiary care center experience in Punjab, North India


1 Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Obstetrics and Gynecology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India

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Date of Submission01-Feb-2022
Date of Decision16-Feb-2022
Date of Acceptance18-Feb-2022
Date of Web Publication02-Jun-2022
 

   Abstract 


Background: Thalassemia and hemoglobinopathies are a group of inherited conditions characterized by abnormalities in the synthesis or structure of hemoglobin (Hb). According to estimates, approximately 7% of the world population is a carrier of Hb disorders, leading to high morbidity and mortality. To reduce the burden of these highly prevalent monogenic disorders, detecting them in the carrier stage is crucial to prevent disease progression. Aim: We aimed to estimate the prevalence and spectrum of hemoglobinopathies in females in the reproductive (20–40 years) age group. Settings and Design: It was a retrospective observational study carried out for 2.5 years (from January 2018 till June 2020). Material and Methods: All the females in the age group of 20–40 years age whose blood samples were received in the department for High-Performance Liquid Chromatography (HPLC) were included. The cases with abnormal HPLC findings were analyzed for hematological parameters including hemoglobin, RBC count, and RBC indices [mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), & red cell distribution width - coefficient of variation (RDW-CV)]. Statistical Analysis: Statistical package for social science (SPSS) statistics 21 version for Microsoft Windows (Chicago, USA) was used for statistical analysis of data. The data were described in terms of range, mean ± standard deviation (SD), frequencies (number of cases), and relative frequencies (percentage) as appropriate. Results: During the study period, 72.2% of the females were affected with β-thalassemia trait, followed by HbD Punjab trait (17.8%), HbQ India trait (2.9%), β-thalassemia major (1.8%), and two cases (1.2%) each of HbS trait, HbD Iran trait, and compound heterozygous of HbD Punjab and β-thalassaemia, whereas HbE trait, compound heterozygous of HbQ and β-thalassemia, compound heterozygous of HbJ-variant and β-thalassemia had one case each (0.6%). Conclusion: Preventive strategies are cost-effective and include population screening, premarital screening, screening of spouses, genetic counseling, and prenatal diagnosis. Educating the carrier females about the potential risk and various screening methods may help in controlling the disease.

Keywords: Hemoglobinopathies, north India, thalassemia, young females


How to cite this URL:
Narang V, Jain A, Grover S, Soni A, Narang M, Taneja A. Prevalence and spectrum of haemoglobinopathies in females of reproductive age group- A first tertiary care center experience in Punjab, North India. Indian J Pathol Microbiol [Epub ahead of print] [cited 2022 Dec 9]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=346511





   Introduction Top


Thalassemia and hemoglobinopathies are a group of inherited conditions characterized by abnormalities in the synthesis or structure of hemoglobin (Hb). According to various estimates, approximately 7% of the world population is a carrier of Hb disorders, leading to high morbidity and mortality. Therefore, it is pertinent to detect the carrier stages as early as possible to prevent disease progression and halt the inheritance to further generations. The clinical presentation of hemoglobinopathies varies from being completely asymptomatic to severe transfusion-dependent anemia. Investigations to determine the genetic burden of Hb disorders during antenatal care are thus the need of the hour. The routine hematological parameters including RBC indices provide significant clues which can help in early diagnosis. Other advanced techniques like high-performance liquid chromatography (HPLC) should also be done to diagnose thalassemia and hemoglobinopathies, especially in antenatal/females of reproductive age group screening.[1],[2],[3],[4]


   Material and Methods Top


This was a retrospective study carried out for 2.5 years (from January 2018 till June 2020). Ethical clearance for the study was obtained from the institutional ethical committee vide IEC no DMCH/P/2018/1099.

All the females in the age group of 20–40 years age whose blood samples were received in the hematology laboratory for HPLC were included. Screening of hospital computer database was done to retrieve records about relevant clinical information and investigations.

HPLC was performed using the Biorad variant D-10 instrument. HPLC report and chromatogram were generated for every case where different peaks were identified in defined windows with relevant information like retention time, the relative percentage of hemoglobin fractions, and total area.

An elaborative hematological workup including hemoglobin, RBC count, and RBC indices [(Mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), & red cell distribution width-coefficient of variation (RDW-CV)] was carried out in all the cases with abnormal HPLC findings. It was performed on a 7-part differential automated hematology analyzer (Coulter LH 750 analyzer) which works on the principle of electrical impedance.

Statistical analysis

Statistical package for social science (SPSS) statistics 21version for Microsoft windows (Chicago, USA) was used for statistical analysis of data. The data were described in terms of range, mean ± standard deviation (SD), frequencies (number of cases), and relative frequencies (percentage) as appropriate.


   Results Top


During the study period, a total of 2509 females (mean age 28.07 ± 4.30 years) were screened. Of the 2509 females, 212 displayed (8.48%) abnormal HPLC patterns concerning Hb A2, Fetal hemoglobin (HbF), or abnormal peaks. Of these 212 patients, 169 patients (79.7%) had been further classified as beta-thalassemia or other specific hemoglobinopathies. The remaining 43 (20.2%) patients had borderline HbA2 levels (3.6%–3.9%).

Out of all 169 cases, the majority (91/169, 53.8%) belonged to the Hindu community, followed by the Sikh community (74/169, 43.8%), and two cases (1.2%) each of Jain and Muslim communities.

Of the 169 females, the majority (n = 122; 72.2%) were affected with β-thalassemia trait, followed by HbD Punjab trait (n = 30; 17.8%), HbQ India trait (5, 2.9%), β-thalassemia major (3, 1.8%) and two cases (1.2%) each of HbS trait, HbD Iran trait, and compound heterozygous of HbD Punjab and β-thalassaemia, whereas HbE trait, compound heterozygous of HbQ and β-thalassemia, compound heterozygous of HbJ-variant & β-thalassemia had one case each (0.6%) as mentioned in [Table 1].


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   Discussion Top


Thalassemia is characterized by reduced synthesis of one or more globin chains, and hemoglobinopathies occur due to the presence of structurally abnormal hemoglobin. The birth of a β-thalassemia major child poses an emotional and financial burden on both family and society. On one hand, heterozygous cases are mostly asymptomatic and get detected during anemia workup, whereas on the other hand, homozygous patients suffer and have significant morbidity with the need for regular blood transfusion along with the increased risk of infections, growth retardation, endocrine dysfunctions, which can affect the quality of life. Therefore, it can be prevented by population screening, premarital counseling, genetic counseling, and prenatal diagnosis. Routine hematological indices along with HPLC can assist in early diagnosis and prevention of birth of an affected child. The variations in the spectrum of different hemoglobinopathies with regards to age, gender, and regions are known, but the data remains limited in this context.[3],[5],[6]

In India, the estimated prevalence of pathological hemoglobinopathies is 1.2/1000 live births with β-thalassemia major (3%–4% with the birth of 8,000 to 10,000 new thalassemia major cases annually), and sickle cell syndrome (approximately 4.3% cases) being the commonest cause of morbidity and mortality, leading to both economical and psychological burden on the individual, family, and society. In Punjab state, approximately 700 to 800 new β-thalassemia major births are reported every year.[2],[5],[7] Yet, only a few studies are available providing data related to various hemoglobinopathies in terms of incidence, prevalence, morbidity, and mortality. Herein, we present the data in terms of the spectrum and prevalence of various hemoglobinopathies at our center. The spectrum of various hemoglobinopathies was in accordance with that of a multicenter study conducted by Mohanty et al.[5] However, the prevalence of the β-thalassemia trait (4.86%) was higher in our study as compared to Mohanty et al. (3.96%). In another study from Punjab, Sharma et al.[6] reported a prevalence of total hemoglobinopathies as 4.53% as compared to 6.73% in our study with that of individual hemoglobinopathy as shown in [Table 3]. The higher prevalence in our study could be due to the selection of all females of reproductive age irrespective of their marital/pregnancy status. An effort was made to compare similar studies from other regions of India [Table 3]. It was observed that beta-thalassemia trait and HbD Punjab were rare in other regions, and HbS was prevalent in the study from Central India.[7],[8],[9]

HbD Punjab was the second commonest hemoglobinopathy detected in the present analysis followed by HbQ India. HbD Punjab syndromes are not uncommon and are relatively under-diagnosed and are clinically heterogeneous, with heterozygous patients being asymptomatic whereas compound heterozygous states like HbS/D and HbD/beta-thalassemia present with chronic hemolytic anemia requiring frequent red cell transfusions. Hb Q India is an uncommon alpha-chain structural hemoglobin variant seen in North and West India. Patients are mostly asymptomatic and often present in the heterozygous state or coinherited with beta-thalassemia. Harrison A et al.[10] reported 0.4% (31/7530) prevalence of Hb Q India in their analysis of over 7 years. Of these, 25 (0.3%) patients had HbQ India trait, and 6 (0.1%) patients had compound heterozygosity for HbQ India and beta thalassemia trait (HbQ India-BTT).[7],[9],[10]

During this present analysis, it was observed that beta thal trait patients had more anemia and low mean lower mean corpuscular as compared to Hb D Punjab and Hb Q India. The anemia was microcytic hypochromic [Table 2]. The findings were comparable to Khera et al., Srinivas et al., and Dhawale et al.[11],[12],[13] Therefore, simple routine hemograms along with peripheral blood smear examinations can give us significant clues in diagnosing hemoglobinopathies.


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Table 3: Comparison of Distribution of various types of hemoglobinopathies amongst Indian studies

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Moreover, public awareness along with various preventive measures may help in the reduction of disease burden. We present this study as additional data about hemoglobinopathies in the reproductive age group female population of Punjab state. We also emphasize that premarital screening should be opted as the mode of a preventive measure as antenatal detection of hemoglobinopathies generates physical and emotional stress for the individual, couple as well as family.


   Conclusion Top


Preventive strategies are cost-effective and include population screening, premarital screening, screening of spouses, genetic counseling, and prenatal diagnosis. Educating the carrier females about the potential risk and various screening methods may help in controlling the disease. In this study, we targeted the females of the reproductive age group (20–40 years) irrespective of their marital/pregnancy status, which are the potential source of amplification of disease magnitude. We think that educating an unmarried female carrier and her family may have a better impact on controlling the disease progression.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Weatherall DJ. Postgraduate Hematology. Hemoglobin and the Inherited Disorders of Globin Synthesis. 5th ed. Vol. 2. Oxford Blackwell Science; 2005. p. 245-55.  Back to cited text no. 1
    
2.
Department of Health and FamilyWelfare Punjab. NRHM State Action Plan; 2010-2011.  Back to cited text no. 2
    
3.
Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 2008;86:480-7.  Back to cited text no. 3
    
4.
Madan N, Sharma S, Sood SK, Colah R, Bhatia HM. Frequency of b –thalassemia trait and other hemoglobinopathies in northern and western India. Indian J Hum Genet 2010;16:16-25.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Mohanty D, Colah RB, Gorakshakar AC, Patel RZ, Master DC, Mahanta J, et al. Prevalence of β -thalassemia and other haemoglobinopathies in six cities in India: A multicentre study. J Community Genet 2013;4:33-42.  Back to cited text no. 5
    
6.
Sharma A, Uppal N, Kukreja S, Kaur M, Kaur S. Screening of thalassemia in pregnant females visiting tertiary hospital in Amritsar. Int J Clin Biochem Res 2020;7:226-31.  Back to cited text no. 6
    
7.
Bhukhanvala DS, Sorathiya SM, Sawant P, Colah R, Ghosh K, Gupte SC. Antenatal screening for identification of couples for prenatal diagnosis of severe hemoglobinopathies in surat, South gujarat. J Obstet Gynaecol India 2013;63:123-7.  Back to cited text no. 7
    
8.
Balgir RS. Hematological profile of hemoglobinopathies in maternal health and reproductive outcome in pregnant mothers at a tertiary hospital in central India. J Hematol Mult Myeloma 2018;3:1012.  Back to cited text no. 8
    
9.
Sur D, Chakravorty R. Prevalence of hemoglobinopathies and thalassemia carriers in women of reproductive age group especially the prospective mothers: A single center study at West Bengal. J Hematol 2016;5:99-102.  Back to cited text no. 9
    
10.
Harrison A, Mashon RS, Kakkar N, Das S. Clinico-hematological profile of Hb Q India: An uncommon hemoglobin variant. Indian J Hematol Blood Transfus 2018;34:299-303.  Back to cited text no. 10
    
11.
Khera R, Singh T, Khuana N, Gupta N, Dubey AP. HPLC in characterization of hemoglobin profile in thalassemia syndromes and hemoglobinopathies: A clinicohematological correlation. Indian J Hematol Blood Transfus 2015;31:110-5.  Back to cited text no. 11
    
12.
Srinivas U, Pati HP, Saxena R. Hemoglobin D-Punjab syndromes in India: A single center experience on cation-exchange high performance liquid chromatography Hematology 2010;15:178-81.  Back to cited text no. 12
    
13.
Dhawle M, Methwani A, Tangde A, Bindu R. HBQ-India: An uncommon hemoglobin variant. Int J Res Med Sci 2018;6:1687.  Back to cited text no. 13
    

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Correspondence Address:
Ankita Soni,
Department of Pathology, Dayanand Medical College and Hospital, Tagore Nagar, Ludhiana - 141 001, Punjab
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_2_22




 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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