Introduction

Thalassaemia is the commonest inherited blood disorder in Malaysia with a total population of 8681 in 2018. This condition is characterised by low haemoglobin levels, due to defects in either the alpha- or beta-globin chain of the red blood cells, leading to an imbalance in globin chain, thus destruction of the red blood cell and ultimately, low haemoglobin presenting as anaemia [1]. The commonest clinical subtype of thalassaemia in Malaysia is Hb E-beta thalassaemia (34.37%), followed by beta thalassaemia major (33.52%), Hb H disease (18.26%), beta thalassaemia intermedia (9.37%) and others (4.48%) [2]. People with a more severe spectrum will require 3– 4-weekly blood transfusions for survival and are categorized as havingtransfusion dependent thalassaemia (TDT).

Beta thalassaemia major followed by HbE-beta thalassaemia have the most serious clinical presentation with poor growth, chronic lethargy and organ failure from chronic anaemia [3]—taking its toll on a person's physical capabilities when medical management is inadequately provided. Life-long regular blood transfusion is required for survival from a young age, when they have to endure hours of blood transfusion and later in life, when iron overload occurs due to transfusion, hours of chelation with Deferoxamine, the infusion type of iron chelating agent. Otherwise, they would have to ingest oral iron chelating agents which could be unpalatable or unaffordable to some. The required medical attention causes their daily activities to be disrupted with a life bound by activities that required their presence at the hospital. This disruption in life is also costly. They have to be responsible for themselves in managing their own health, finances and family when they reach adulthood—which had been a huge burden experienced by their caretakers when they were young [4]. Without optimal treatment and responsibility, not only will their growth be affected in terms of distorted body images such as short stature, thalassaemic facies and 'child-like' appearance [4], they could also face social stigmatization from 'frequent absenteeism' or poor physical performance, which then lowers their self-esteem and causes mental stress [5].

The prolongation of life expectancy for people with TDT through advancement and availability of necessary treatment has enabled them to experience adulthood [6,7,8]. In 2018, 92% of thalassaemics registered in the National Registry were still alive in Malaysia and around 44% have reached adulthood. They have been receiving assistance such as provision of free medical treatment and mass community screening [9, 10]. The TDT population continues to grow. Although there is a decline in the number of new cases, many more will be entering adulthood soon [9].

A report has shown that the global disability-adjusted life years increased by 40% for non-communicable diseases when life-expectancy is prolonged [11]. This could be a warning of the future that people surviving with TDT will have to face. People with TDTs are known to have expressed their concerns about how they have struggled with life and how they have been marginalized [5, 12], but there were limited studies, if any, about their actual adulthood needs, employment and perception of healthcare services. The perception of having thalassaemia has also been negative since childhood, a burden to the patient, family and nation [4, 13]. The social media continue to publish their challenges intermittently despite the government’s contemporary assistance [14,15,16,17]. Therefore, it is timely to explore how they fare during adulthood in the era when much medical assistance is provided. We conducted this study to determine their clinical and psychosocial burden, including employment status and their actual needs during adulthood. We also aimed to assess if there is another area of focus for the healthcare team to support TDTs during their transition to adulthood.

Methods

Study design

This was a cross sectional study and eligible participants were recruited through convenient sampling.

Patients from the thalassaemia units of two hospitals in Penang, Malaysia and or members from all registered regional thalassaemia societies in Malaysia were approached face-to-face by their attending doctor, nurse or selected regional site coordinators who worked for the regional thalassaemia society from all over Malaysia between August 2016 and December 2016.

Those in-charge of recruitment (research assistants, RA) were briefed about the aims and conduct of the study, and trained on recruitment process. Once a written consent was obtained, participants were given an option to complete the questionnaire either by an electronic link to Google form or a hard printed copy. The questionnaires were to be self-completed without any assistance or interference from RA. Participants were given up to an hour to complete the questionnaire. The completed questionnaires in hard copies were then sealed by the participant in an envelope, which would then be collected, compiled and send as bulk mail back to the investigators by the RA. As for the electronic questionnaires, all submissions were done online and the responses were automatically stored at a pre-set google form which could only be accessed by investigators.

Sample size estimation

We used a survey sample size calculator according to sample size formula for a finite population. A sample size of 344 respondents was determined from a level of confidence set at 95%, a margin of error at 5%, a population proportion of 0.5, and a population size of 3200 (from the estimated adult TDT registered in Malaysia [18, 19]. A total of 450 questionnaires were distributed to account for the possibility of incomplete information.

Participants (inclusion and exclusion criteria)

Participants were recruited when they fulfilled the inclusion criteria of having transfusion dependent thalassaemia (TDT) as diagnosed by their doctors at the time of recruitment, and aged 18 years and above. Those who were not capable of answering the questionnaire independently were excluded.

Assessment and outcome measures

The structured questionnaire consisted of four sections on (a) socio-demographics characteristics, (b) their health status and well-being, (c) quality of life and (d) free text on employment, challenges and healthcare systems.

Details of the self-administered questionnaire are as follows:

  1. (a)

    Socio-demographic characteristics: Age, gender, race, type of thalassaemia, co-morbidity, medication, marital status, education, income and occupation.

  2. (b)

    Healthy Days Core Module (CDC HRQOL-4) [20, 21]: This is part of the National Health and Nutrition Examination Survey (NHANES) used in the National Commission for Quality Assurance's (NCQA) Healthcare Effectiveness Data and Information Set (HEDIS), and in this study, the focus was on thalassaemia. There are 4 self-rated questions. The first question is on respondent's perception of own general health in a 5-point Likert scale and the subsequent questions require the respondents to estimate the number of days they felt unhealthy physically, mentally and when daily activities were limited, for the past 30 days.

    This set of questionnaires is only available in English and was translated to Malay and Chinese languages. The translations were cross-checked and back translated to ensure accurate and true representation of the original document.

  3. (c)

    WHOQOL-BREF [22]: This is an abbreviated version of the World Health Organization Quality of Life questionnaire (WHOQOL 100) which comprised of two individual questions on perception and satisfaction in QOL, and questions that assessed four QOL domains (physical health, psychological health, social-relationship, environmental health). Responses are graded on a scale 1–5. Each response for a particular domain was then added up to form a cumulative score that has a maximum value of 100. A higher score indicates a better QOL for a particular domain. This set of questionnaires is available in three languages: English, Malay and Chinese, which were used.

  4. (d)

    Perception of healthcare services and employment: The questions included job descriptions, job’s satisfaction, monthly salary, monthly off-days, support at work, discrimination at work, disclosure of disease and willingness to disclose disease with colleagues. Participants were given the opportunity to elaborate on any questions asked including areas which could be related to healthcare services in the form of free field texts.

Both the questions on biodata and perception of healthcare services and employment were developed by the investigators using an iterative process, piloted on a small sample of adult thalassaemia patients and modified according to feedback obtained. The questionnaire was made available in the three major languages used in Malaysia: English, Malay and Chinese.

Participants were given a choice to choose depending on their language literacy.

Endpoints

The study endpoints focused on the participants perception of general health and quality of life, and their perception on healthcare services and employment. This study then further identified factors that were significantly associated with the quality of life of these TDT participants.

Statistical analysis

In reporting descriptive statistics, continuous data was presented as mean with standard deviation (SD) and categorical data presented as frequency (n) with percentage (%). Chi-square analysis (X2) was conducted to compare the baseline characteristics according to the age at diagnosis and the age receiving first blood transfusion. Data obtained from Healthy Days Core Module and WHOQOL-BREF were displayed using the respective intended unit or scores.

Linear regression analysis was used to determine potential factors associated with their QOL. All study factors were identified as clinically important variables. Simple linear regression was used to identify possible factors associated with QOL. The factors were then fitted into multiple linear regression models based on each QOL domain, adjusting to the effect of other study factors. The results from linear analysis were reported as coefficient, its 95% confidence interval (CI) and p-value. All statistical analysis was done using Stata-13 [23]. A p-value of less than 0.05 was taken as a statistically significant finding.

Results

Of the 450 questionnaires distributed to 13 states of Malaysia, 217 were returned which accounted for 43.6% response rate. Twenty-one responses were excluded because of less than 80% completion of the questionnaire. The final number of questionnaires analysed was 196. The responders came from nine out of the 13 states.

There were fairly equal proportion of males (44%) and females (56%) participants. The mean age was 27 (SD 7.4). They were mainly of the Malay ethnicity (62%). The majority of them suffered from beta thalassaemia major (64%), followed by HbE beta thalassaemia (30%) and HbH disease) (6%) (Table 1).

Table 1 Socio-demographic characteristics (n = 196)
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We found that 45% of the participants were suffering from at least one complication of thalassaemia or the treatment they had received (Table 1). Highest co-morbidity on the list was musculoskeletal problems (13%) such as osteoporosis-osteopenia syndrome, bone pain or fractures or disfigurements, followed by endocrine issues (12%) such as diabetes mellitus, hypothyroidism or infertility and cardiac abnormalities (3%). Other health issues included transfusion related infections (2%) and psychological problems (2%) such as depression and anxiety. Among the participants, 8% had various types of complications and another 9% did not make any disclosure. Hence, 82% of participants were on some form of medication in addition to their regular blood transfusion and folate supplements. Almost all (97%) participants were on iron chelating agents to prevent iron overload (Table 1).

Effects of having chronic anaemia and dependency on blood transfusion

We found 62% of those participants with beta thalassaemia major to be diagnosed and transfused before the age of 2 years. Another 12% were diagnosed as having thalassaemia before the age of 2 years but started their first transfusion after 2 years old and the remaining 26% were diagnosed and had first transfusion after 2 years (Table 2). The majority of those with thalassaemia intermedia (HbE beta thalassaemia and HbH disease) manifested much later and 3.5% needed medical care before age of 2 years. At the time of this study, all participants were transfused at least once a month and these transfusions were conducted at hospitals only on weekdays during office hours. Further hospital visits were expected for various reasons such as doctor/pharmacist consultations and investigation procedures, thus causing 58% of the participants to require hospital visits twice or more per month. There were significantly more singles among those who were diagnosed and were transfused blood earlier (p ≤ 0.001) but no significant association between the timing of diagnosis and transfusion with co-morbidity, education and employment status. (Table 2).

Table 2 Chronic anaemia and dependency on blood transfusion (n = 196)
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Perception of general health and quality of life

In general, the participants considered their health to be between 'Good' and ''Very Good'. Within 30 days, the participants experienced an average (mean (SD)) of 5.6 (5.2) unhealthy days, whereby a mean (SD) of 3.1 (3.0) days could be due to being physically unwell and 2.6 (3.5) days being mentally unwell. We found a mean (SD) of 2.5 (3.3) days when their daily activities were affected and limited.

The overall perception of QOL rating and health satisfaction was 3.7 (0.8) and 3.5 (0.7) on a Likert scale of 1–5 with the value 5 as excellent or very satisfied. For perception in QOL ratings, majority of the participants rated themselves to be in a very good QOL state (53%), followed by good (33%), excellent (11%), very poor (2%) and poor (1%). Most of them were satisfied with their health (47%), another 41% were neither satisfied nor dissatisfied, the remaining rated very satisfied (7%), dissatisfied (4%) and very dissatisfied (1%). Their quality of life across all 4 domains was above 60 out of a maximum score of 100, with psychological health obtaining the highest score at 64.7 (15.7) and environmental health getting the lowest score at 60.8 (16.7) (Table 3).

Table 3 Perception of healthy days and quality of life (QOL)
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Perception on healthcare services and employment

At the time of the study, 64% participants held a job. Majority (44%) earned between RM1000 and RM2000 a month, followed by 38% earning below RM1000 a month and 3% participants did not disclose their monthly earnings. 6% of the working participants were not confident in retaining their current employment. The remaining (36%) participants were not earning a living because they had never held any job (27%), had been retrenched for the past 2 years (39%) or were students (34%). Of those participants with working experiences, 41% were willing to disclose their thalassaemia status, 82% had shared their thalassaemia condition with colleagues, 34% had received satisfactory workplace support, 77% had experienced difficulties in their job because of thalassaemia and 57% reported discrimination for having thalassaemia. There was no significant association between their perception of employment difficulties because of thalassaemia and the number of overall unhealthy days (p = 0.32), or between the number of days when activities were affected by physical and or mental issues and their perception of employment difficulties because of thalassaemia (p = 0.06). Among those with working experience, at least 12% have chosen not to give a response to at least one of the questions in this section.

There were 67 responses to the free text comments on their healthcare services and employment. The main response was a negative perception of having thalassaemia and how it had affected their job potentials (35 responses), followed by 21 responses which pleaded for more employment opportunities or promotions for people with thalassaemia and less workforce discrimination. The reasons for the discrimination were their frequent absenteeism from work, easy fatigue and being short or ugly. There were six responses expressing dissatisfaction with health service provision such as non-flexi treatment hours or no dedicated clinics, 20 responses on conflicting judgement or ability in prioritising between health and job, and 18 responses about poor public empathy were expressed. Six participants wanted more community awareness and support together with a better health professional-patient relationship in order to enable them to cope with having thalassaemia and another five participants wanted assistance in planning for their future.

Factors associated with quality of life (WHOQOL-BREF)

Table 4 showed the factors associated with QOL. Results from the simple linear regression showed that there were three main factors significantly associated with QOL: having days with mental issues (reduced the scores for all four domains), higher education (increased the physical health, social relationship and environmental health scores) and higher monthly income (increased the physical health and social relationship scores) (Table 4).

Table 4 Linear regressions on sociodemographic, CDC healthy-days and employment associated with WHOQOL-BREF scores
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When multiple linear regression was applied, having a higher monthly income remained a significant factor which increased the scores for physical health and social health, and additional significant result for environmental health. The other factors that continued to play a role on QOL domains were: days when activities were affected by physical and or mental issues (associated with physical health and psychological health), Malay ethnicity (associated with psychological health and environmental health), being single (associated with social relationship) and days affected by mental issues (associated with social relationship).

Discussion

This study has shown that despite having thalassaemia, the majority of the participants perceived their general health status as good. Their quality of life (QOL) scores for all domains were above 60 out of a 100 (maximum score). Our scores were almost comparable with the scores from other similar studies [24, 25]. When compared the age- and sex-matched WHOQOL-BREF scores between TDTs and non-thalassemic adults in Italy, Floris 2018 reported that thalassemia subjects had scores which were at least as good as those of non-thalassemic subjects in all domains; with TDTs obtaining the highest score (SD) at 73(19) in social relationships domain and the lowest score at 63 (14) in environmental health domain. A study by Gan 2016 reported its highest score with environmental health domain at 67.38 and lowest score with physical health domain at 62.03.

Our findings suggested that the participants most likely could have received adequate and appropriate medical treatment early in life because the majority have no other co-morbidities, have gained employment and have completed at least secondary education. Such achievements would be their main concerns and struggles in life seven to ten years ago [4, 26]. The ability to obtain higher educational level has also been used as a benchmark towards a higher social level, better QOL and a better income [25,26,27,28]. Our multiple linear regression of factors has shown that having good income may lead to an increased QOL in physical health, social health and environmental health. These predictors to a better QOL were similar to another study which reported higher odds of higher income, more financial resources, better access to healthcare and lower co-morbidities to higher education [25].

The number of unhealthy days measured by CDC HRQOL-4 in this study were lower when compared with other chronic diseases such as diabetes, respiratory problems, arthritis, heart disease and mental disorders [29, 30]. Although comparatively lower, the participants in this study needed to spend at least four days every month to care for their illness. Based on our multiple regression, any additional unhealthy days with or without limitation to activities may significantly lower the QOL scores.

The participants in this study could be considered relatively young and unmarried. Hence, this could have contributed to the comparatively “higher” QOL scores. We are uncertain whether they are able to maintain or improve their QOL further as they grow older especially when some people with TDT could have been using defective coping strategies since teenage years as reported in some studies [13, 31]. They have to learn to juggle between staying healthy with the disease and doing well with normal activities. Life-training skills, self-care management and psychological treatment have been suggested as healthcare management strategies to people with TDTs to lead an independent life with good QOL and health [32,33,34]. These should start during their childhood and perhaps be extended to their caregivers as indicated by other studies [35, 36]. With proper training and guidance, they may fare as well as the people without the disease [37].

Based on the small number of responses to the open question, a number of participants in this study perceived having thalassaemia as a burden to their employment and working life. Their expressions, from being discriminated against, having unsupportive colleagues and friends, being inhibited from developing to their full potentials, getting a lower salary to and being fearful of losing their employment due to their frequent time-away from work, described some restrictions they have been facing. Such challenges were similarly voiced in their thalassaemia social media platform [38]. These concerns seemed to contradict the participants' perception of a good health and QOL. Therefore, there is a need for qualitative studies such as focused group interviews to assess the validity of these concerns, their actual needs and the root cause of the issue.

Meanwhile, perhaps shared consultations with other specialized teams in the healthcare system would enable people with thalassaemia to seek support and treatment, all occurring within a same hospital visit [39,40,41]. This may help to reduce the demand for time off from work, and financial and transportation issues experienced by many participants. Healthy social and professional integration such as anti-stigma campaigns for mental illness [42] could be considered to create a better social and environmental support for TDTs. By recognizing this group of people as valuable assets to the community and provide them equal opportunities, they could move at a faster rate towards a full social and professional life [43]. In addition, publishing the success stories of some patients could boost not only their self-esteem but also perhaps change the degree of stigmatization on them that is still present in some communities, just like in cases of AIDS and obesity [44, 45]. As one of the participants said "I am as capable like everyone else, it's just that I need a little extra blood every month".

Strength of the study

This study provides some insight about the well-being of the adult population with TDT in Malaysia using validated questionnaires and semi-structured questions on employment status and working life. Although there are other studies on this matter, the population of interest in these studies was more focused at selected regional places. This study captured some voices of people with TDTs with regards to the challenges they were still facing.

Limitations of the study

The main limitation in this study is the small sample size and unequal distribution of samples collected. We faced difficulties reaching most TDTs due to various reasons such as participatory refusal, poor internet coverage and lost mails. Nevertheless, we have managed to collect some data from the two regions with the largest number of registered people with thalassaemia (31%) in Malaysia, according to the latest registry [2]. Another limitation is that we could not do any comparison with healthy adults matched by age and gender. The WHOQOL-BREF questions were also rather lengthy and sensitive, probably causing some participants to choose not to answer some questions in the sections relating to social relationship and environmental health. Perhaps another healthcare and QOL tool specially tailored for thalassaemia such as ThALI should be used [46].

Conclusion

The majority of the participants in this study seemed to be coping with the disease, and moving into adulthood with a fairly good quality of life and comparatively lower number of unhealthy days with limitation to daily activities. Some continued to face suppression of their potential capabilities and other challenges. Their future now not only depends on how to stay healthy but also how to live a near normal life just like the general population without chronic illnesses. Future qualitative studies are needed to focus on their perceived needs and to look for more tailored supportive approaches.