International Journal of Science and Healthcare Research Vol.2; Issue: 3; July-Sept. 2017 Website: www.gkpublication.in/ijshr.html Original Research Article ISSN: 2455-7587

Prevalence of Sickle Cell in : A Prospective Study in Tertiary Health Center

Dr. Kuntal Devesh Patel1, Dr. Bhavya Saxena2, Dr. Mansi Balar2, Dr. Sahil Parikh2, Dr. Bhavik Shah2, Dr. Vaibhavi Chaudhari2, Dr. Jasmin Jasani3

1Assistant Professor, 2Resident Student, 3Professor, Department of Pathology, S.B.K.S.M.I. & R.C., Sumandeep University, Vadodara, Gujarat. 391760

Corresponding Author: Dr. Kuntal Devesh Patel ______

ABSTRACT Keywords: , Sickle cell anemia, , , Background: Sickle cell disease comprises a trait group of diseases characterized by the presence of HbS. It is classified as sickle cell anemia (Hb INTRODUCTION SS), hemoglobinopathy SC, hemoglobinopathy A group of genetic disorders of SD, S-beta thalassemia (Hb S-beta) and other hemoglobin are termed as associations of mutant hemoglobin with Hb S. . They affect 4.5% of Sickle cell disease is the most common inherited the world population. [1] The prevalence of disorder worldwide. Pregnancy in sickle cell disease is at high risk. β- thalassemia trait and sickle cell in India Methods: This prospective study was conducted varies between 3-17% and 1-44% on pregnant females OPD in DGH from 1st respectively because of consanguinity and [2] January to 1st April 2017. Consenting caste and area endogamy. Every year, ten participants were interviewed using a pre- thousand children with β- thalassemia major structured questionnaire. All the data were are born in India, which constitutes 10% of tabulated according to parameters: age, literacy, the total number in the world. [3] Inherited anemia, gestational age, parity and HPLC hemoglobin disorders are an important findings. cause of morbidity and mortality. The Result: The total numbers of pregnant women curative treatment like bone marrow screened for hemoglobinopathy were 2500. 6.4 transplantation is costly and so prevention is % had positive sickle solubility tests. Further HPLC analysis was done in the second group the cost effective strategy, which includes population screening, genetic counseling and 5.8 % showed hemoglobinopathies. 44.13% [4-6] were in 1st trimester, 28.96 % were in 2nd and prenatal diagnosis. trimester and 26.89 % were in last trimester. Sickle-cell anaemia (also known as Majority of the female (57.24%) attended ANC sickle-cell disorder or sickle-cell disease) is OPD for the first time, out of which 22 (26.50 a genetic blood disorder, where the blood %) were in first trimester, 41 (49.39%) were in cells contain abnormal hemoglobin (Hb S) nd 2 trimester and the rest of 20 (24.09%) were in called sickle hemoglobin. As a result Red last trimester. And there were 62 women visited Blood Cells which are normally discoid in OPD as followup checkup. shape, become sickle shaped when they are Conclusion: In present study, gravid population exposed to low oxygen levels. has higher prevalence of hemoglobinopathy (5.8 %), mainly SCT (94.48 %). More efforts are Sickle cell disease (SCD) comprises required to increase awareness in high risk a group of diseases characterized by the populations concerning sickle cell anemia presence of sickle hemoglobin (Hb S). It is before the dream to control hemoglobinopathy classified as sickle cell anemia (Hb SS), in India. hemoglobinopathy SC, hemoglobinopathy SD, S-beta thalassemia (Hb S-beta) and other associations of mutant hemoglobin

International Journal of Science and Healthcare Research (www.gkpublication.in) 59 Vol.2; Issue: 3; July-September 2017 Kuntal Devesh Patel et al. Prevalence of Sickle Cell Anemia in Pregnancy: A Prospective Study in Tertiary Health Center with Hb S. Sickle cell disease is the most cell births through screening and common inherited disorder worldwide with referring her for genetic counseling. varying clinical severity and potentially serious complications. REVIEW OF LITERATURE Pregnancy in sickle cell disease is at James Herrick, a physician first very high risk. Many reports have described the characteristic sickle shaped documented a substantial maternal risk of red cells in a medical student from Grenada morbidity and mortality and high perinatal in 1910. [10-11] adverse consequences. Women with SCD Linus Pauling and his colleagues presented have an increased risk of pre-eclampsia and that sickle haemoglobin (HbS) had an maternal death, stillbirths, preterm altered electrophoretic mobility and they deliveries, and small-for-gestational-age were the first to define it as a molecular newborns. The prevalence of sickle-cell disease in 1949. [10] anaemia is extremely common in the tribal The first report of sickle hemoglobin belt of Southern and Central parts of India (Hb S) in India was by Lehman and Cut which includes tribal in the states of bush in 1952 in the tribal populations in the Gujarat, Madhya Pradesh, Maharashtra, Nilgiri hills in south India (hills of Chhattisgarh, Orissa, Tamil Nadu and Tamilnadu) and later discovered in other Kerala. [7-9] states. [3] The incidence varies from 5 % to Sickle cell trait individuals are 34 % and it is mainly restricted to the tribal absolutely normal and healthy, unless they [12] have a special blood test investigation for A few years later in 1957, Vernon Hb S electrophoresis or HPLC. Ingram discovered that sickle hemoglobin Confirmation of patient suffering from resulted from a single amino acid sickle cell disease is carried out only by substitution in the hemoglobin molecule. [13- laboratory investigations only. Therefore 14] blood examination in antenatal cases at In the same year, Dunlop and large is needed to estimate the load of cases Mazumderlike wise reported the occurrence and carriers of sickle cell haemoglobin- of sickle hemoglobin in the tea garden opathies. workers of Upper Assam who were migrant The present study was an effort labourers from tribal groups in Bihar and which had been made to assess and identify Odisha. [21] Since then, many population the pregnant women with sickle cell disease groups have been screened and the sickle or the carriers of sickle cell disease and look cell gene has been shown to be prevalent for the prevalence in the selected group. among three socio-economically disadvantaged ethnic groups, the scheduled AIM AND OBJECTIVE tribes, scheduled castes and other backward AIM classes in India. [14-20] To screen samples of ANC women and The prevalence of sickle cell carriers among then to find prevalence of sickle cell different tribal groups varies from 1 to 40 anemia percent. [10] Madhya Pradesh has the highest load with an estimated number of 9,61,492 OBJECTIVES sickle heterozygotes and 67,861sickle To create awareness about genetic homozygotes. [14] Further, 27 of the 45 inheritance of SCD amongst entire districts in Madhya Pradesh fall under the community. sickle cell belt and the prevalence of HbS To survey the common perinatal varies from 10 to 33 percent. [10] It has also problems of future mother having sickle been estimated that 13,432 cell anemia. Prevention of spread of would be at risk of having a child with sickle cell disease by reducing sickle sickle cell disease in this state and the

International Journal of Science and Healthcare Research (www.gkpublication.in) 60 Vol.2; Issue: 3; July-September 2017 Kuntal Devesh Patel et al. Prevalence of Sickle Cell Anemia in Pregnancy: A Prospective Study in Tertiary Health Center expected annual births of sickle For this study, collection of Blood homozygotes would be 3358. [22] samples were done according to practical High prevalence of sickle gene has manual of Dacie. [23] The blood samples been established in various tribal were mixed on electric blood mixture for 8 communities of Gujarat including Bhils and to 10 minutes and subsequently analyzed on Dhodias of Panchmahal, Dhanka, Gamit, the coulter LH750. All EDTA samples will Vasava, Bariya, Varli, Vaghari, Kukna, be screened for PBS(Peripheral blood Halpati,Dublas, Naikas, Koli, Chaudhari smear) examination and Sickling solubility etc. [23] test. Tribal accounts 15 % of the total The positive solubility test samples population of Gujarat and distributed in were further screened for subtyping of various districts of the state such as Hemoglobinopathy. These samples were Sabarkantha, Banaskantha, Panchmahal, analyzed on the Bio-Rad Variant I HPLC Vadodara, Narmada, Bharuch, Surat, system to check for the quantification of Valsad, Dang and Div-Daman [23-24] variants of hemoglobin. The raw data were integrated and chromatograms were MATERIALS & METHODS generated. All the data had been collected This prospective cross-sectional and evaluated. study was conducted on pregnant females Based on hemoglobin level, anemia attending ANC (Anti Natal Care) OPD in was classified as per WHO severity grading Dhiraj General Hospital, Piparia, for a criteria. Thus anemia in pregnancy ranges period of three months from 1st January from mild (>10.0g/dl), moderate (7.0 - 2017 to 1st April 2017. Most of patients 9.9g/dl) to severe (<7.0 g/dl). The typing of were from tribal background and lower anemia was done as per standard PBS socioeconomic status. examination method. Before conducting the study, Statistical analyses were undertaken permission was obtained from the Human using Chi-square test, mean, percentages Research Review Penal (HRRP) of SBKS and proportions. P values less than 0.05 MIRC and Institutional Ethics Committee were considered significant. (SVIEC) of Sumandeep Vidyapeeth for consideration of ethical aspects and final RESULTS approval. The total number of pregnant Women included in this study were women screened for hemoglobinopathy was in their steady state for a long period of time 2500 from ANC OPD of Dhiraj General without any chronic systemic illness or Hospital, Piparia, for a period of three other diseases which could affect the months starting from 1st January 2017 to 1st hematological parameters. Subjects who April 2017. have been transfused in the last 3 months 160out of total screened women (6.4 were excluded from the study and those %) had positive sickle solubility tests. The who are not willing to participate. sickling test is dithionate qualitative Consenting participants were solubility test, which is only for screening. interviewed using a pre-structured Therefore there could be some chances of questionnaire. The information like name, false positive results and that’s why they age, sex, address, education, socio- must be confirmed with HPLC or Hb economic status, previous transfusion electrophoresis. history, sibling history, consanguinity any Further HPLC analysis was done in family history of blood disorders, etc., were the second group and 145, showed filled in according the proforma. Data were hemoglobinopathies (5.8 %). We had collected accordingly and recorded in evaluated 145 samples with positive HPLC Microsoft Excel. results for further studies.

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Additional findings apart from hemoglobinopathies, nutritional anemia was very much prevalent in and largely The following Table 4 is showing neglected due to lack of education amongst hemoglobinopathy based on HPLC finding. pregnant women. But those supplementary findings had not been evaluated further. Table: 4: Distribution of hemoglobinopathy based on HPLC finding. All the data were charted and tabulated Hemoglobinopathy No. of Women Percentage according to mentioned parameters: age, (Sample size- 145) (%) SCT(Sickle cell trait) 137 94.48 literacy, anemia based on Hb level, SCD(Sickle cell Disease) 03 2.06 gestational age, parity and HPLC findings. Thalassemia minor 05 3.44 Thalassemia major 00 00 The demographic profile of the study Other 00 00 population is shown in Table 1& 2.

Table: 1. A: Age of pregnant women in study population. Out of 145 samples, 137 samples Age No. of females Percentage were having HbS level between 30%-45%, (years) (Total-145) (%) <20 20 13.79 HbA between 50%-70% and HbF was <1%. 21-25 83 57.24 This was confirmed by HPLC. The overall 26-30 34 23.44 31-35 06 4.13 prevalence of hemoglobinopathies was 145 >35 02 1.37 (5.8 %), comprised of 137 (94.48%) cases Age (in years), Mean (SD) 23.8 (1.45) - of SCT,3 cases (2.06%) of SCD and 5 cases

Table: 1. B: Education of pregnant women in study (3.44%) of beta thalassemia minor. population. No. of females Percentage (Total-145) (%) DISCUSSION Illiterate 38 26.20 Hemoglobinopathies though are Left schooling midway 68 46.89 Finished schooling 36 24.82 common worldwide, but some geographic Graduation 03 2.06 areas and some populations having higher

Table: 2: Distribution based on parity of the pregnant women prevalence of it comparatively. Parity No. of female Percentage In India, According to hospital based (Sample size- 145) (%) study, average frequency of sickle cell gene 1 82 56.55 2 49 33.79 is around 5%. The highest frequency of 3 10 06.89 sickle cell gene in India is reported in Orissa >3 04 02.75 (9%), followed by Assam (8.3%), Madhya Out of 145 women, 64 (44.13%) were in 1st Pradesh (7.4%), Uttar Pradesh (7.1%), [27- trimester, 42 (28.96 %) were in 2nd trimester Tamil Nadu (7.1%) and Gujarat (6.4%). 29] and 39 (26.89 %) were in last trimester. Majority of the female (57.24%) attended The prevalence of sickle cell trait ANC OPD for the first time, out of which (5.8 %, n= 2500) in our study is in 22 (26.50 %) were in first trimester, 41 concordance with the reported prevalence of [26] (49.39%) were in 2nd trimester and the rest the study by P. Ashwin et al. of 20 (24.09%) were in last trimester. And The majority (50.34%) of anemic there were 62 women visited OPD as follow women demonstrated moderate anaemia up check-up. while mild and severe anaemia were Following table 3 are showing the degree of recorded in 65 (44.82%) and 07 (4.82%) anemia based on the hemoglobin level. pregnant women respectively. The severity of anaemia according to age groups is Table: 3: Degree of anemia in study group. Degree of anemia No. of women Percentage shown in Table 5.The results are concordant [30] (Hb level) (Total -145) (%) with the study by A. Nadeem et al. Mild (>10.0g/dl) 65 44.82 Moderate (7.0 - 9.9g/dl) 73 50.34 according to which 50.86% of anemic Severe(<7.0 g/dl) 07 4.82 women demonstrated moderate anaemia.

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Table: 5: Anemia with its age wise distribution, in pregnant women Sr. No. Age (years) Degree of anemia Mild Moderate Severe Total numbers of women (145) No. (%) No. (%) No. (%) 1 <20 10 (6.89) 8 (5.51) 2 (1.37) 20 2 21-25 50 (34.48) 31 (21.37) 2 (1.37) 83 3 26-30 2 (1.37) 31 (21.37) 1 (0.68) 34 4 31-35 2 (1.37) 2 (1.37) 2 (1.37) 6 5 >35 1 (0.68) 1 (0.68) 0 (0) 2 Total 65 (44.82) 73 (50.34) 7 (4.82) 145

The peripheral smear acknowledged group (χ2=28.38, p<0.001) and educational normocytic hypochromic and microcytic (χ2=19.58, p<0.001). Other factors such as hypochromic blood picture to be most family structure (χ2=1.46, p>0.05) and common morphological variant of anaemia. dietary habits (χ2=2.37, p>0.05) were not These two pictures of PBS are characteristic significantly associated with anemia. All the of iron deficiency anaemia. Underlying β women with multiple pregnancies were thalassemia trait could have been missed in found to be anemic, though it was only this group and investigations for iron moderate in nature. deficiency followed by repeat HPLC after Following table 6 is showing anemia with iron therapy is needed. its correlation with educational status. A highly significant association of anemia was found with the mother‘s age

Table:6: Anemia with its correlation with educational status. Educational status Degree of anemia Total (145) Mild Moderate Severe No. (%) No. (%) No. (%) p<0.001 Illiterate 4 (2.75) 4 (2.75) 30 (20.68) 38 Left schooling 27 (18.62) 33 (22.75) 8 (5.51) 68 Finished schooling/Matrix finished 30 (20.68) 5 (3.44) 5 (3.44) 36 Graduation finished 3 (2.06) 0 (0) 0 (0) 3 Total (145) 64 (44.13) 42 (28.96) 39 (26.89) 145 P<0.001

In this study a high prevalence of educational status and income. [25-26] These anaemia among pregnant women was findings are significantly matching with the observed. The majority had moderate present study. anaemia. Most of the anemic pregnant women were in the younger age group. This CONCLUSION result was in concordant with the results Studied gravid population has higher obtained by similar study in the rural area of prevalence of hemoglobinopathy (5.8 %), Delhi where patients in the age group (20- mainly SCT (94.48 %). 24 years) showed maximum prevalence of One of the limitations of this study is anaemia. [25] small sample size, so that could affect the The prevalence of anaemia was not prevalence of hemoglobinopathy. There is significantly related with structure of also a need for screening of whole family, birth interval and number of population by calculating sample size from abortions. This result corresponds well with the pilot study in high risk community in those of Bentley/Griffiths. [22] Women with near future. first ever pregnancy more often had severe The most effective approach to anaemia. The observed very high prevalence minimize the problem of of anaemia and its severity in the current hemoglobinopathies in females in India is study is similar to earlier studies. [23,24] by increasing literacy rate, sensitization and As in other studies the severity of screening of individual, genetic counseling, anaemia was inversely related to proper health education regarding the nature

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