Table of Contents    
ORIGINAL ARTICLE
Year : 2018  |  Volume : 9  |  Issue : 2  |  Page : 236-241  

A clinico-epidemiological study of thalassemia cases in India


Department of Community Medicine, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India

Date of Web Publication20-Jun-2018

Correspondence Address:
Nitin Joseph
Department of Community Medicine, Kasturba Medical College, Manipal University, Light House Hill Road, Mangalore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jnsbm.JNSBM_224_17

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   Abstract 

Introduction: Thalassemia is the most common single-gene disorder in India. Hence, care of these patients becomes a priority issue. Objectives: This study was done to assess the clinical presentations and management practices in thalassemia. Materials and Methods: Case sheets of patients with thalassemia admitted over the past 10 years from 2005 to 2014 were examined and recorded in a validated pro forma. Results: Of the total 183 cases, 179 (97.8%) were of beta thalassemia major, 3 (1.6%) of beta thalassemia intermediate, and 1 (0.6%) of beta thalassemia minor category. The median age at diagnosis was 1 year. Hardly, one-fourth of the cases were diagnosed in the first 6 months. Majority of cases were under-fives 58 (31.7%) and were males 116 (63.4%). Fever was the most common presenting symptom 34 (18.6%). Pallor 179 (97.8%) followed by hepatomegaly 172 (94%) were the most common signs. Bone deformities were reported in 13 (7.1%) cases. Among the under-fives, more than one-third were underweight and more than half were stunted. The mean posttransfusion value of hemoglobin after 1 year of transfusion among cases was 10 ± 1.6 g percent. Iron chelation therapy using desferrioxamine was given to 51 (27.9%) cases. The mean age of starting this therapy was 11.1 ± 8.2 years. Splenectomy was done in 4 cases, all of them being cases of beta thalassemia major. The mean age while performing splenectomy was 10.7 ± 4.8 years. Lenticular opacity was present among greater proportion of thalassemia cases on treatment with desferrioxamine (P = 0.022). Conclusion: Several complications were identified among thalassemia cases. A multidisciplinary care approach is therefore required for solving these problems.

Keywords: Clinical features, complications, record-based study, thalassemia, treatment


How to cite this article:
Joseph N, Pai S, Sengupta S, Bharadwaj S, Dhawan S, Khare K. A clinico-epidemiological study of thalassemia cases in India. J Nat Sc Biol Med 2018;9:236-41

How to cite this URL:
Joseph N, Pai S, Sengupta S, Bharadwaj S, Dhawan S, Khare K. A clinico-epidemiological study of thalassemia cases in India. J Nat Sc Biol Med [serial online] 2018 [cited 2018 Oct 22];9:236-41. Available from: http://www.jnsbm.org/text.asp?2018/9/2/236/234713


   Introduction Top


Thalassemia syndromes are caused by inherited mutations that decrease the synthesis of either alpha or beta globin chains of hemoglobin. Imbalance in globin chain synthesis results in anemia, tissue hypoxia, and red cell hemolysis.[1] Individuals with beta thalassemia major or homozygous type manifest with severe transfusion-dependent anemia. Those with beta thalassemia minor or heterozygous genotype present with mild asymptomatic anemia. The heterogeneous variant of moderate severity is called beta thalassemia intermedia.[1]

Thalassemia syndrome is endemic in Mediterranean basin, Middle East, tropical Africa, Indian subcontinent, and Asia.[1] In India, it is the most common single-gene disorder.[2] Every year one-tenth of the world's thalassemic population are born in India.[3] The carrier rate for beta thalassemia gene ranges from 1% to 3% in southern and 3% to 15% in northern parts of India.[4],[5],[6] There is lack of prevention programs in India to contain the incidence of thalassemia births.

Thalassemia affects physical growth and delays maturation. Its management also imposes a huge economic burden on the families of the affected.[7]

Experiences from other endemic countries in Europe have shown that public education followed by screening and genetic counseling can substantially reduce the incidence of thalassemia.[8],[9]

Hospital-based registers give a good approximation of the disease pattern in the community when there is unavailability of formal population-based screening of hemoglobinopathies.

With this background, this study was done in Mangalore city where previous studies have reported a high carrier rate of thalassemia among certain castes.[5],[10] The objectives of this study was to assess the pattern, clinical presentations, complications, and management practices among thalassemia cases.


   Materials and Methods Top


This retrospective record-based cross-sectional study was conducted in January 2015 in two major hospitals affiliated to a medical college. The study was approved by the Institutional Ethics Committee. Permission to do the study was taken from the medical superintendents of the respective hospitals. The secondary data of all confirmed cases of thalassemia within 10 years period from 2005 to 2014 were examined by the investigators. The information regarding sociodemographic details of the patients, type of thalassemia, risk factors such as family history of genetic disorders, history of consanguinity among parents, symptoms, signs, and complications associated with thalassemia, hematological reports, and management practices were recorded in a predesigned validated pro forma. Data were entered and analyzed using SPSS Inc., Chicago, IL version 11.0. Chi-square test, Fisher's exact test, paired t-test, and Mann–Whitney U-test were used to test association between variables. Two-tailed P < 0.05 was considered statistically significant association.


   Results Top


Out of the 183 thalassemia cases, 179 (97.8%) belonged to beta thalassemia major, 3 (1.6%) of beta thalassemia intermediate, and 1 (0.6%) of beta thalassemia minor category.

Mean age of cases was 10.1 ± 9.3 years, and median age was 8 years. Mean age at diagnosis was 2.3 ± 2.4 years, and median age at diagnosis was 1 year. The age at diagnosis ranged from 0.1 to 11 years. Majority of cases were under-fives 58 (31.7%) and were males 116 (63.4%) [Table 1].
Table 1: Sociodemographic distribution of thalassemia patients

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Family history of thalassemia was positive among 7 (3.8%) cases and family history of other genetic diseases was positive among one case.

History of consanguineous marriage was positive among 7 (3.8%) cases, three involving marriages between second degree relatives and four involving third-degree relatives.

Associated genetic disorders were reported in three cases and associated hemoglobin anomalies in two cases each.

Fever was the most common presenting symptom 34 (18.6%). Pallor 179 (97.8%) followed by hepatomegaly 172 (94%) were the most common signs among cases. Bone deformities were reported in 13 (7.1%) cases, all of which were beta thalassemia major cases [Table 2].
Table 2: Distribution of clinical features among thalassemia patients (n=183)

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Data on weight for age were available only among 46 out of 58 under-fives and 32 out of 112 patients aged between 6 and 19 years. 18 (39.1%) out of 46 under-fives were underweight compared to 17 (53.1%) out of 32 among 6–19 years age group (P = 0.222).

Data on height for age were available only among 21 out of 58 under-five patients. Proportion of under-fives with stunting was 11 (52.4%). The anthropometric indices of thalassemia cases did not vary significantly with gender [Table 3].
Table 3: Age- and gender-wise distribution of anthropometric indices among thalassemia cases

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Among those aged above 20 years, anthropometric data were available only of three cases. It comprised of an underweight male and a male and female of normal weight. Therefore, the total proportion of under-weight cases in this study were 36 (44.4%) out of 81.

Hemoglobin electrophoresis was the method of diagnosis in all the cases. Blood transfusion was given to all cases except for the lone case of beta thalassemia minor. The mean number of blood transfusions over the past 1 year was 10.8 ± 3.3 ranging from 6 to 17. 44 (24%) cases underwent transfusion at least once a month in the past 1 year.

The baseline pretransfusion value of hemoglobin was mentioned for 168 cases, and its mean was 7.3 ± 1.7 g/dl. With respect to beta thalassemia major patients (n = 165), the mean baseline hemoglobin value was 7.3 ± 1.7 g/dl [Table 4]. Among beta thalassemia intermediate patients (n = 2), baseline hemoglobin values were 5.8 g/dl and 8.9 g/dl, and in the lone beta thalassemia minor patient, it was 8.6 g/dl.
Table 4: Distribution of hemoglobin values before blood transfusion among beta thalassemia major patients

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The posttransfusion value of hemoglobin after 1 year of transfusion was mentioned for 151 patients, and its mean was 10 ± 1.6 g/dl. It was found to significantly increase compared to mean baseline values (paired t-test t = 19.3, P < 0.001) [Table 5].
Table 5: Distribution of hemoglobin values among thalassemia cases during pre- and 1-year posttransfusion phase

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Peripheral blood picture findings were mentioned for 23 cases. Among them, microcytic red blood cells (RBCs) were seen in 22, hypochromic RBCs in 9, anisocytosis in 4, and poikilocytosis in 2 cases.

Analysis of various blood parameters showed HbF, HbA2, serum ferritin, aspartate transaminase, and alkaline phosphatase to be on the higher side while mean corpuscular volume (MCV) and HbA on the lower side among majority of thalassemia cases [Table 6].
Table 6: Distribution of various laboratory investigation parameters among thalassemia cases

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Among beta thalassemia major patients, the mean values of MCV (n = 27) was 70.5 ± 17.1 fl, MCH (n = 26) was 23.9 ± 7.6 pg, HbA2 (n = 179) was 6.5%, HbA (n = 179) was 21.6%, and HbF (n = 179) was 64.6%. The HbF values ranged from 4.9% to 97.8% among cases of beta thalassemia major.

Serum ferritin ranged from 154.7 to 11086 pmol/L among 68 cases with a mean of 3572.9 ± 2426.1 pmol/L.

Iron chelation therapy using desferrioxamine was given in 51 (27.9%) cases. It was given to 50 (27.9%) out of 179 cases with beta-thalassemia major. Among cases (n = 51) in whom desferrioxamine was given, mean serum ferritin values at the start of therapy was 3832.9 ± 2393.3 pmol/L. The mean age at starting desferrioxamine therapy was 11.1 ± 8.2 years with a median age of 10 years.

Other medications such as folic acid were given to 93 (50.8%) cases. Splenectomy was done in 4 cases, all of which were cases of beta thalassemia major. The mean age of cases while performing splenectomy was 10.7 ± 4.8 years, with a median age of 11 years and minimum age of 5 years.

Complication in the form of hemosiderosis as a result of repeated blood transfusion was reported in one case.

Lenticular opacity was reported in five cases. It was associated with treatment history of desferrioxamine (P = 0.022) [Table 7].
Table 7: Association between iron chelating agent and development of lenticular opacity among thalassemia cases

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There was no association of serum ferritin levels with development of lenticular opacity among cases (Mann–Whitney U-test, P = 0.395).

All the thalassemia cases included in this study were reported to have survived.


   Discussion Top


The proportion of cases diagnosed within first 6 months in this study was much lesser than the proportion ranging from 46.7% to 60.7% in other parts of India.[7],[11],[12] Hence, awareness of this condition needs further improvement at this setting.

Fever was the most common symptom among cases probably due to associated infections. Pallor was the most common sign in this study similar to the findings of other studies.[13],[14]

Hypertrophy of maxilla was present in 7 cases, all of which were beta thalassemia major cases. Their mean age of starting blood transfusion was 7 ± 3.4 years. This emphasizes the need of routine dental care in all thalassemia patients, along with initiation of blood transfusions from an early age to prevent maxillary deformities, in accordance to standard guidelines.[15]

In this study, 44.4% patients were underweight compared to 23.6%[16] and 45.7%[17] reported in other studies. Proportion of cases with stunting in the Iranian study was 65.7% which was more than our observations.[17] Failure to thrive results from feeding problems, irritability, and intercurrent infections.[15] Hence, nutritional care is very important in the management of thalassemia.

The mean number of blood transfusions in a Sri Lankan study was 10.4 in the past year which was similar to our observations.[18] In the study done at Ahmedabad, India, the frequency of transfusion was once or more in a month among 25.6% cases which was also similar to our findings.[19] This was in accordance with guidelines where the usual frequency of one transfusion every 2–4 weeks is recommended among thalassemia cases so that hemoglobin level is maintained more than 9–10.5 g/dl.[15],[20] This blood transfusion regimen promotes proper growth and prevents bone marrow expansion and iron overload among most patients.[21] The posttransfusion hemoglobin also should not be >14–15 g/dl, as it can lead to greater risk of hyperviscosity and stroke.[21] In this study, the mean posttransfusion level of hemoglobin was 10 g/dl indicating appropriate transfusion practices as per guidelines.[21] Furthermore, transfusion in severe thalassemia genotypes as per the guidelines usually starts within the first 2 years of life.[15] It was observed here that in only 22 (12%) cases (all of major variety), blood transfusion was initiated within the age of 2 years. The median age at the start of transfusion among severe cases was 6 months in the study done in Iran which was much earlier than our observations.[17]

Peripheral blood picture findings such as anisopoikilocytosis observed in few cases were also reported in a Pakistani study.[22] In the Saudi Arabian study, microcytosis was more frequently seen among adults than children.[23] This was also similar to our observations wherein out of 22 cases with microcytosis, 20 were reported among patients aged ≥15 years (P = 0.425).

In this study, all cases which underwent splenectomy were of major type. As per guidelines when the annual transfusion requirements rise above 200 ml/kg/year, splenectomy may be considered to reduce the rate of iron loading.[15] These splenectomized patients in this study had a mean weight of 21.4 kg and had an average of 15 transfusions/year which was thus in accordance to the guidelines. All these cases were operated after the age of 5 years. As per standard guidelines, splenectomy is to be avoided in children <5 years due to increased risk of fulminant postsplenectomy sepsis.[15] In other studies, splenectomy was performed in 18%[18] and 37%[24] thalassemia cases.

Serum ferritin correlates well with body iron stores and is an easier and reliable method to monitor iron overload and evaluate the efficacy of chelation therapy.[15],[25] The Hong Kong-based study [24] reported the mean serum ferritin level as 5140 pmol/L (range 468–48490 pmol/L) and a New Delhi, India-based study [11] reported mean value as 5262.5 pmol/L (range 2471.7–14156.1 pmol/L) among all cases of thalassemia which was more than our findings. Previous studies reported better prognosis of thalassemia following the control of serum ferritin levels in the body.[26],[27]

Ferritin levels <2500 ng per mL or 5617.5 pmol/L are associated with improved survival.[28] In the present study, 13 (19.1%) out of 68 and in the Sri Lankan study [18] almost 50% cases had serum ferritin levels above the potentially cardiotoxic level.[28]

Complication in the form of hemosiderosis as a result of repeated blood transfusion was reported in one case in this study. Moderate-to-severe hemosiderosis was observed in 35% thalassemia cases in the Hong Kong-based study.[24]

Use of iron binders or chelators is the only solution to remove this excess iron as the body cannot do so by itself. Patients who have had 10-20 transfusions or those with serum ferritin levels >2247 pmol/L should be started on iron chelation therapy as per standard guidelines.[15]

In the present study, injectable iron chelation therapy in the form of desferrioxamine was given to more than one-fourth of the patients and their mean serum ferritin values at the start of therapy was 3832.9 ± 2393.3 pmol/L. This chelating agent was used between 42.2% and 100% cases in other studies.[11],[17],[18],[24] Desferrioxamine which is given subcutaneously or intravenously is an expensive and cumbersome treatment but being relatively nontoxic has been the treatment of choice.[15],[29] It was started below 3 years of age among 5 cases in this study. The median age of initiating desferrioxamine therapy was 3.5 years in the Hong Kong-based study.[24] There has been reports of skeletal abnormalities such as abnormal linear growth and metaphyseal dysplasia in children treated with desferrioxamine before the age of 3 years that have prompted recommendations for later therapy.[15],[30] The Sri Lankan study also reported desferrioxamine-induced arthropathy in 8 cases.[18] Oral chelating agents such as deferasirox or deferiprone were not used among any cases in this study.

The study done in New Delhi, India [11] reported lenticular opacities among 40% thalassemia patients which was much more than our observations. Its significant association with history of use of desferrioxamine reported in the same study,[11] and this study, indicates its occurrence as a complication of iron chelation therapy. The former study [11] found that lenticular opacities were significantly more among females and those with higher serum ferritin level, which was different from our observations. All the cases with lens opacities were below the age of 20 years in this study as also reported among most cases in the former study.[11]

Folic acid deficiency has been reported in thalassemia major and intermedia because of increased erythropoiesis. Daily oral supplementation with 1 mg of folic acid is recommended for persons with low hemoglobin levels.[15] Supplementation also reduces the risk of thrombosis.[15] Therefore, in this study too, folic acid was given in more than half of the cases.

With the medical advances in conventional management practices in the recent years, the prognosis of thalassemia cases has improved to a large extent.[31] Survival of patients has crossed 40 years with regular blood transfusion and with appropriate chelation therapy.[31],[32] In this study, all cases with thalassemia survived. However, in the study done in Hong Kong, 8.6% of cases died, with cardiomyopathy as the leading cause of death.[24]


   Conclusion Top


Most of the cases belonged to severe variety of beta thalassemia. However, the proportion of cases diagnosed within first 6 months was hardly one-fourth. Hence, awareness of this condition needs improvement at these settings. This will improve carrier identification, genetic counseling, and prenatal diagnosis among high-risk groups carrying thalassemia traits for minimizing its incidence.

Among the under-fives, more than one-third were underweight and more than half were stunted. Hence, good nutritional care along with calcium and Vitamin D supplement needs to be given among the diseased to prevent growth impairment.

Hypertrophy of maxilla was seen in few cases, and their mean age of starting blood transfusion was 7 years. This emphasizes the need of routine dental care in all thalassemia patients and initiation of blood transfusions within 2 years of age in severe thalassemias.

Serum ferritin levels were above the potentially cardiotoxic level in 19.1% cases in this study. Hence, its periodic monitoring followed by timely initiation of iron chelation therapy is a must to improve prognosis among cases.

Desferrioxamine was given in more than one-fourth of the cases. However, it was started within 3 years of age in few cases. In such patients, monitoring of bone and growth development is required added with controlled doses of chelating agents.

Lenticular opacity was significantly associated with usage of desferrioxamine among patients. Hence, cases on this therapy need to be periodically screened for ocular morbidities.

Although the survival rate has improved, the quality of life of these patients needs to be improved by a multidisciplinary care approach to cater to their nutrition, dental, orthopedic, and ophthalmic problems identified in this study.

Limitations

Findings were limited to the availability of information stated in the medical records.

Acknowledgments

We thank the medical superintendents of the respective hospitals for their cooperation in the conduct of this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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