Demographic and clinical profiles of patients with β-thalassemia major treated at Dubai Thalassemia Centre: A retrospective study

Rabah Almahmoud; Amal Hussein; Fatheya Al Khaja; Ahmed Farrag Soliman; Hany Dewedar; Sarah Mathai

doi:10.4103/abhs.abhs_41_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 1 | Issue : 4 | Page : 237-241

Demographic and clinical profiles of patients with β-thalassemia major treated at Dubai Thalassemia Centre: A retrospective study

Rabah Almahmoud¹, Amal Hussein², Fatheya Al Khaja³, Ahmed Farrag Soliman³, Hany Dewedar³, Sarah Mathai⁴
¹ Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
² Department of Family and Community Medicine and Behavioral Sciences, Sharjah, United Arab Emirates
³ Dubai Thalassemia Centre, Dubai Health Authority, Dubai, United Arab Emirates
⁴ Department of Pediatrics, Christian Medical College, Vellore, Tamil Nadu, India

Date of Submission	20-Jun-2022
Date of Decision	13-Sep-2022
Date of Acceptance	21-Sep-2022
Date of Web Publication	18-Oct-2022

Correspondence Address:
Rabah Almahmoud
Clinical Sciences Department, College of Medicine, University of Sharjah, PO BOX 27272, Sharjah
United Arab Emirates

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/abhs.abhs_41_22

Abstract

Background: β-thalassemia major (BTM) is one of the hereditary anemias that is inherited as autosomal recessive. It is complicated by iron overload in different organs including the heart, liver, and endocrine glands. This study aimed to look at the demographic of patients with BTM treated at Dubai Thalassemia Centre. Methods: Demography and clinical data for all thalassemia patients between 2 and 45 years of age were collected. Data such as age, gender, nationality, frequency of blood transfusion, and ferritin level among different groups were calculated. Results: A total of 351 patients were studied; men constituted 50.7% (n = 178) compared with women 49.3% (n = 173). Young children (2–9 years) made up 11.1% (n = 39) of the total population studied, whereas older children and adolescents (10–18 years) made 20.2% (n = 71), and adults (19–45 years) made 67.7% (241). UAE nationals constituted 38% of the total population compared with 44% in previously published studies. Also, the percentage of Emirati children has dropped significantly from prior years (46.3% to 19.9%). The mean pre-transfusion hemoglobin ranged between 9.69–10.2 g/dL in all age groups indicating a successful hyper-transfusion policy. The median Ferritin level was significantly higher among women aged 19–45 years (3255 µg/L) as compared with men (2160 µg/L; U = 5488, P = 0.034) in the same group, and this was not observed in the other groups. Conclusion: The success of the premarital screening program implemented by the UAE government was evident in the drop in the percentage of Emirati children affected by BTM in our study.

Keywords: Demography, ferritin, pre-transfusion hemoglobin, thalassemia

How to cite this article:
Almahmoud R, Hussein A, Al Khaja F, Soliman AF, Dewedar H, Mathai S. Demographic and clinical profiles of patients with β-thalassemia major treated at Dubai Thalassemia Centre: A retrospective study. Adv Biomed Health Sci 2022;1:237-41

How to cite this URL:
Almahmoud R, Hussein A, Al Khaja F, Soliman AF, Dewedar H, Mathai S. Demographic and clinical profiles of patients with β-thalassemia major treated at Dubai Thalassemia Centre: A retrospective study. Adv Biomed Health Sci [serial online] 2022 [cited 2023 Jun 9];1:237-41. Available from: http://www.abhsjournal.net/text.asp?2022/1/4/237/358843

Background

The first description of a patient with β-thalassemia in modern medicine dates back to 1925 when Dr. Cooley described a series of children with splenomegaly and distinct facial features [1]. β-Thalassemia major (BTM) is a group of autosomal recessive inherited blood diseases that arises because of pathological transformation (β⁺) and/or deletion of the β globin gene (β⁰), resulting in rapid red blood cells breakdown and anemia. This happens because of the unpaired accumulation of α globin, which is damaging to the cell membranes and leads to ineffective erythropoiesis [2]. There are three main clinical phenotypes of thalassemia: thalassemia major, thalassemia intermedia, and thalassemia minor. Thalassemia major is the most severe form of thalassemia syndromes and children with this disorder usually present in the first two years of life with failure to thrive, progressive pallor, and distended abdomen due to splenomegaly [3]. They develop severe anemia and become dependent on frequent and likely regular blood transfusions throughout their life. As the disease progresses, patients develop distinct thalassemia facies that includes frontal bossing, depressed nasal bridge, maxilla hypertrophy, and prominent malar eminence, along with growth failure and massive hepatosplenomegaly [3]. When left untreated, the natural course of the disease is death during the first decade, mostly from congestive heart failure. With the progression of thalassemia, and with a combination of blood transfusion and increased iron absorption from the gastrointestinal system, patients develop multiple complications from iron deposition in various organs, for example, heart, liver, and endocrine glands [4]. This pathological process is responsible for the systemic manifestation of the disease in the form of growth failure, hypogonadism, hypothyroidism, diabetes mellitus, and heart failure or arrhythmias, which is the most common cause of mortality [5,6].

β-thalassemia is more common in certain regions of the world including the Mediterranean, Middle East, South East Asia, and Indian Subcontinent region [7]. The United Arab Emirates (UAE)) is an Arab country located in the Middle East region. In a study that was carried out in 2011, the prevalence of β-globin gene defects was reported as 8.5% in the UAE [8]. More recent studies reported a similar rate which is considered as one of the highest in the Middle East and North Africa (MENA) region [9]. This high prevalence is attributed largely to the consanguineous marriage in the country, as this was found to be as high as 50% of the marriages which has driven the government to launch a premarital screening program in 2011 [10,11]. In the UAE, Dubai thalassemia centre is regarded as the largest centre for treating patients with BTM. A retrospective study was carried out with the aim to describe the demographic and clinical characteristics of thalassemia patients in the UAE.

Materials and methods

Study design and collection of data

In this study, demographic and clinical data pertaining to all patients with BTM, above 2 years of age attending the Dubai Thalassemia Centre, were collected from November 2019 to May 2021. Data that were extracted from the patients’ medical records included patient’s name, date of birth, nationality, and diagnosis. The diagnosis of BTM was based on clinical presentation and confirmed by hemoglobin electrophoresis and DNA analysis.

Data analysis

Patients’ data were entered into Excel and were then imported into the Statistical Package for Social Sciences (SPSS) software program, version 28.0 for data coding and statistical analysis. Descriptive statistics, including frequencies, percentages, means, and medians were reported as appropriate to the type of data. The measures of dispersion standard deviation (SD), and interquartile range (IQR reported as Q1–Q3) were reported for quantitative data showing normal or skewed distributions, respectively. Normality of continuous data was tested graphically using histograms and Q–Q plots and statistically using the Kolmogorov–Smirnov test. Chi-square test was used for studying the association between categorical variables. The independent t-test was used to investigate the relationship between a normally distributed outcome and a dichotomous factor, whereas Mann–Whitney U test was used when the outcome variable had a skewed distribution. One-sample Wilcoxon signed-rank test was used to compare a median value to a hypothetical value. One-way analysis of variance (ANOVA) was used to compare three or more means, whereas Kruskal–Wallis test was used to compare three or more medians. Levene’s test was used to check for the equality of variances. The level of significance was set at 5% and thus a value of P ≤ 0.05 indicates statistical significance.

Ethical approval

The study was approved by Dubai Scientific Research Ethics Committee at Dubai Health Authority, Reference (DSREC-06/2019-10).

Results

The study included data pertaining to a total of 351 thalassemia patients visiting the Dubai Thalassemia Centre between November 2019 and May 2021. Among the patients, 11.1% (n = 39) were aged from 2 to 9 years, 20.2% (n = 71) were 10 to 18 years, 57.0% (n = 200) aged 19 to 35, and 11.7% (n = 41) were from 36 to 45 years. Male patients represented 50.7% (n = 178) of the total study sample, whereas 49.3% (n = 173) were women.

Patients 2–9 years

A total of 39 patients were between 2 and 9 years, of whom 48.7% (n = 19) were men, whereas 51.3% (n = 20) were women. The mean age in this group was 5.4 years (SD = 2.14). Forty-one percent (n = 16) of patients were UAE nationals, 25.6% (n = 10) were Arabs and 30.8% (n = 12) were non-Arabs. In this age group, all patients were diagnosed with BTM and started blood transfusions at a median age of 244 days (IQR: 182 - 455). The frequency of receiving blood transfusion was either once every three weeks (70.6%, n = 12) or once every three to four weeks (29.4%, n = 5). Over the last 12 months, their mean pre-transfusion hemoglobin level was 9.69 g/dl (SD = 0.83) and the median ferritin level was 2212.5 µg/L (IQR: 1636.5–3180.7) [Table 1].

Table 1: Demographic and clinical characteristics of patients by age group.

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Patients 10–18 years

In this study, there were 33 male patients between 10 and 18 years old with a mean age of 15 (SD = 2.45). Of these patients, 48.5% (n = 16) were UAE nationals, 27.3% (n = 9) were Arabs and 21.2% (n = 7) were non-Arabs. The majority of male patients in this age group (93.9%, n = 31) had BTM. The median age, in days, at starting blood transfusion was 292 (IQR: 164–1108) and the majority (87.9%, n = 29) had transfusions once every 3–4 weeks. Over the past 12 months, their mean pre-transfusion hemoglobin level was 9.71 g/dL (SD = 0.76), whereas the mean ferritin level was 2700.19 µg/L (SD = 1344.48) [Table 1].

A total of 38 female patients between the ages of 10 and 18 were enrolled in this study with a median age of 16.30 (IQR: 13.81–16.78). The majority of these female patients were UAE nationals (39.5%, n = 15), and 92.1% (n = 35) were diagnosed with BTM. Blood transfusion was started at a median age of 335 days (IQR: 108–1255), with transfusion every three or four weeks (89.4%). Over the past 12 months, the mean pre-transfusion hemoglobin was 9.96 g/dl (SD = 1.18) and the median ferritin level was 2384.5 µg/L (IQR: 1613.2–4493.6) [Table 1].

Patients 19–45 years

A total of 241 patients, of age between 19 and 45, participated in this study (52.3% were men and 47.7% were women). Among these patients, 83% (n = 200) were 19–35 years old, whereas the rest (17%, n = 41) aged between 36 and 45.

Male patients had a mean age of 28.8 years (SD = 5.55) and were from different nationalities (34.9% UAE nationals, 23.8% Arabs, and 39.7% non-Arabs). BTM was the most commonly reported diagnosis for male patients in this age group (94.4%, n = 119). For the female patients, the mean age was 29.9 years (SD = 6.18), 37.4% (n = 43) were UAE nationals, 26.1% (n = 30) were Arabs, and 33.0% (n = 38) were non-Arabs. 93.9% (n = 108) of all women were diagnosed with BTM.

The median age for starting a blood transfusion was 270 days for men and 365 days for women. Among the male patients, 51.6% (n = 65) had blood transfusion once in 3 weeks, whereas 23.8% (n = 30) patients required transfusion once in 3–4 weeks. On the contrary, 77.4% (n = 89) of female patients required blood transfusion once in 3 weeks. The median Ferritin level was significantly higher in women (3255 µg/L) as compared with men (2160 µg/L; U = 5488, P = 0.034). Although the level of hemoglobin was higher among women when compared with male patients, with mean values of 10.2 and 9.73g/dL, respectively, yet, this difference was not found to be statistically significant (t test = –1.530, df = 238, P = 0.127) [Table 1].

Discussion

BTM poses a global medical concern. According to the World Health Organization, the annual incidence of BTM is reported in more than 40,000 live births of whom more than 25,500 are blood transfusion dependent [12]. Due to the large population of expatriates, UAE has a variety of patients with BTM from different ethnic backgrounds. The impact of migration has been well recognized and it has changed the natural distribution of BTM across the globe [13]. In a previous study published by the Dubai Thalassemia Centre with data up until 2007, 60% of the subjects were Arabs with UAE nationals constituting 44% of the cohort and the remaining patients were from different parts of the world [14]. In our study, we found that Emiratis constituted 38% of the total BTM population. This drop in the percentage of UAE nationals could be contributed to the success of the premarital counseling program.

A fascinating observation was the striking difference in the young population between this study and the previous study from the same center reported in 2007. Although close to half of the cohort (46.3%) in the previous study were children under 15 years, only 19.9%% of subjects in this study were aged <15 years [14]. This once again may reflect the effect of education and the implantation of pre-marital counseling launched for more than a decade [9]. The vision of the UAE government to reduce the incidence of BTM has paid off and this will definitely set a precedent for other neighboring countries with similar health concerns. Other countries with premarital program have also reported a drop in the prevalence of BTM and other hemoglobinopathies [15].

Till 2007, the standard of care of β-thalassemia patients registered at the Dubai Thalassemia center included frequent blood transfusions and Desferrioxamine as an iron chelator [12]. Desferrioxamine is administered as an infusion thereby limiting patient compliance and putting BTM patients at risk of developing complications of iron overload including cardiomyopathies and endocrinopathies [16,17]. Patients on oral iron chelators were shown to have lower serum ferritin levels [18,19]. In addition, good compliance with iron chelation resulted in better survival [20]. In our study, the median serum ferritin level in the 2–18 year age group was 2361.45 µg/L and was found to be significantly higher than the value reported in a previous study (1943 µg/L) [14]. Although oral chelators have shown to be effective in reducing serum ferritin level [21], the serum ferritin level did not show significant improvement after the introduction of oral chelators despite the expectation, compliance might be a reason behind that, especially in the young population. Our study found no significant difference between men and women in serum ferritin levels in the children and adolescents group. However, women were found to have higher serum ferritin compared with men for which the exact reason could not be pinpointed but it may be due to the fact that women were more compliant with regular blood transfusion.

Further studies are needed to be conducted to look into improving compliance or other early interventions such as bone marrow transplants. Other options especially for adults with BTM may include the use of Luspatercept, an erythroid maturation agent, which is showing promising results in reducing the transfusion burden in this group of patients [22].

Conclusion

In summary, this study provides a follow-up to the previous study describing the changing demographics and the impact of premarital counseling in reducing the prevalence of BTM among the Emiratis population.

Limitations

The main limitation of the study is that it is a retrospective study with its inherent problems.

Acknowledgement

We would like to thank all the patients at Dubai Thalassemia Centre and their families.

Authors’ contribution

RA and SM conceived the research concept. RA, SM, and FA developed the research design. RA, AH, FA, AFS, and HD performed fieldwork and data analysis. Finally, the RA, AH, and SM prepared the first draft and all reviewers reviewed and approved the final draft of the manuscript.

Ethical statement

The study was approved by Dubai Scientific Research Ethics Committee (DSREC)- Dubai Health Authority on July 9, 2019. Reference: DSREC_06/2019_10.

Financial support and sponsorship

The study was funded by a seed grant from the University of Sharjah-United Arab Emirates.

Conflict of interest

There are no conflicts of interest.

Data availability statement

The entire data are available with the principal investigator (RA).

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