Thavorncharoensap et al.

BMC Blood Disorders 2010, 10:1

http://www.biomedcentral.com/1471-2326/10/1

RESEARCH ARTICLE Open Access

Factors affecting health-related quality of life in

Thai children with thalassemia
Montarat Thavorncharoensap1,6*, Kitti Torcharus2, Issarang Nuchprayoon3, Arthorn Riewpaiboon1,
Kaemthong Indaratna4, Bang-on Ubol5

Abstract
Background: Knowledge of the factors associated with health-related quality of life (HRQOL) among patients with
thalassemia is essential in developing more suitable clinical, counseling, and social support programs to improve
treatment outcomes of these patients. In light of the limited research in this area, this study aims to examine
factors associated with HRQOL among children and adolescents with thalassemia in Thailand.
Methods: A cross-sectional survey was conducted in three selected hospitals in Thailand during June to November
2006. PedsQL™ 4.0 Generic Core Scale (Thai version) was used to assess HRQOL in 315 thalassemia patients
between 5 and 18 years of age. Other related clinical characteristics of the patients were collected via medical
record review.
Results: The mean (SD) of the total summary score was 76.67 (11.40), while the means (SD) for the Physical Health
Summary score and Psychosocial Health Summary score were 78.24 (14.77) and 75.54 (12.76), respectively. The
school functioning subscale scored the lowest, with a mean of 67.89 (SD = 15.92). The following factors
significantly affected the HRQOL of the patients: age; age at onset of anemia and age at first transfusion; pre-
transfusion hemoglobin (Hb) level; receiving a blood transfusion during the previous three months; and disease
severity. In addition, iron chelation therapy had a significant negative effect on HRQOL in the school functioning
subscale. In contrast, serum ferritin level, frequency of blood transfusions per year, and gender were not
significantly related to HRQOL among these patients. The results from multivariate analysis also confirmed these
findings.
Conclusions: To improve HRQOL of thalassemia patients, suitable programs aimed at providing psychosocial
support and a link between the patient, school officials, the family and the physician are important, especially in
terms of improving the school functioning score. The findings also confirmed the importance of maintaining a pre-
transfusion Hb level of at least 9-10.5 g/dL. In addition, special care and attention should be given to patients with
a severe condition, and those who are receiving subcutaneous iron chelation therapy.

Background thalassemia traits or are carriers, while 1% of the popu-

Thalassemia is an inherited blood disease. It is a serious lation is afflicted with this disease [4].
public health problem throughout the Mediterranean Thalassemia is a chronic disease that presents a range
region, the Middle East and the Indian subcontinent, as of serious clinical and psychological challenges. The
well as in Southeast Asia [1]. Out of approximately 300 effects of thalassemia on physical health can lead to
million carriers of this hemoglobin disorder worldwide physical deformity, growth retardation, and delayed pub-
[2], 55 million live in Southeast Asia [3]. In Thailand, erty [5-7]. Its impact on physical appearance, e.g., bone
with a population of 65 million, about 40% have deformities and short stature, also contributes to a poor
self-image [6,7]. Severe complications such as heart fail-
ure, cardiac arrhythmia, liver disease, endocrine compli-
cations, and infections are common among thalassemia
* Correspondence: [email protected]
1
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok,
patients [8,9]. The problems mentioned do not only
Thailand affect patients’ physical functioning but also their
© 2010 Thavorncharoensap et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the
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reproduction in any medium, provided the original work is properly cited.
Thavorncharoensap et al. BMC Blood Disorders 2010, 10:1 Page 2 of 10
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emotional functioning, social functioning and school status; while another study [11] found that quality of life
functioning, leading to impaired health-related quality of in the school domain was affected the most.
life (HRQOL) of the patients [6,7,10-14]. Presently, there is limited research examining the fac-
Although thalassemia is recognized as a genetic blood tors associated with HRQOL in children and adolescents
disorder which can be fatal if proper treatment is not with thalassemia. A previous study conducted in adults
received, during the past decades the development of with thalassemia found that treatment and cultural dif-
new treatments and clinical management has markedly ference did not affect HRQOL [7]. Other studies have
improved the prognosis as well as the survival rates of found that age [11] and side effects of iron chelation
the patients [9,15-18]. However, the positive impact of [13,14] are predictors of HRQOL in children with tha-
these treatments is likely to be diminished, especially in lassemia; while gender, ethnicity and household income
terms of HRQOL, if they interfere with daily activities are not [13]. A better understanding of the factors asso-
or are less tolerable. These may be the cases of regular ciated with HRQOL among children and adolescents
blood transfusions that require frequent visits to the with thalassemia could have a direct effect on the devel-
hospital, and nightly subcutaneous injections of iron opment of more suitable clinical, counseling, and social
chelation therapy [14]. support programs to enhance treatment outcomes, espe-
For chronic diseases such as thalassemia, where a cure cially in terms of HRQOL of these patients. In addition,
is not attainable and treatment may be prolonged, at-risk groups of children and adolescents could be
HRQOL is likely to be an essential outcome when con- identified as candidates for proactive care assistance.
sidering options for treatment for individual patients Given the insufficient research in this area, this study
and the allocation of health care resources. In child aims to examine factors associated with HRQOL among
health service research, HRQOL is also recognized as an thalassemic children and adolescents with the focus on
important health outcome [19-21]. As children are less patient perspective.
able to voice their concerns and are more vulnerable
than adults, the assessment of HRQOL in children is Methods
essential for the provision of proper care, since it helps Participants and settings
in identifying the impacts of the disease and treatment The cross-sectional study was conducted among chil-
from the children’s perspective. Moreover, a recent dren and adolescents with thalassemia who received
study found that HRQOL of children can be used as a outpatient treatment at one of three participating hospi-
predictor of health care costs, and can also help identify tals - Phramongkutklao Hospital, King Chulalongkorn
at-risk groups of children who are candidates for proac- Memorial Hospital, and Saraburi Hospital - from June
tive care coordination [22]. to November 2006. Phramongkutklao Hospital and King
Due to the effects of the disease and its treatment, as Chulalongkorn Memorial Hospital are teaching hospitals
mentioned previously, existing evidence indicates that located in Bangkok, while Saraburi Hospital is a regional
thalassemia has a negative impact on HRQOL [6,11-13]. hospital located in Saraburi province (108 km from
A previous study revealed that thalassemia patients Bangkok). Participants in the study were selected based
experienced more depressive symptoms and reported on the inclusion and exclusion criteria specified in
lower HRQOL [6]. In addition, it was found that not Table 1. The demographic characteristics for the sample
only transfusion-dependent patients but also transfu- were later described in Table 2.
sion-independent patients suffered from impaired The sample size required for the study was calculated
HRQOL [12]. By using EuroQoL (EQ-5D), a prior study using the formula by Lemeshow et al. [23]. According to
[13] found that the pain domain of patients was affected the formula, sample size should not be smaller than 30
the most, followed by the depression and mobility times the total number of independent variables. Since
domains, with an equal score. One study [12] found that the number of independent variables in this study is
the most commonly affected domains were feelings such approximately 11, the total sample size required was
as depression, anxiety, and concern about overall health 330.

Table 1 Inclusion and exclusion criteria

Inclusion criteria Exclusion criteria
Patients diagnosed with thalassemia. Patients having impaired cognitive function or having severe clinical
condition, which may limit their ability to participate in the study.
Patients between 5 and 18 years of age. Patients taking oral iron overload treatment.
Patients who had been treated at Phramongkutklao Hospital, King Patients unwilling to participate in the study.
Chulalongkorn Memorial Hospital or Saraburi Hospital since October 1,
2004.
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Table 2 Patient characteristics

N (%)/Mean (SD)
Gender (n = 314)
Male 159 (50.6%)
Female 155 (49.4%)
Age (years) (n = 315) 10.0 (3.3)
Diagnosis (n = 310)
b-thalassemia/Hb E 165 (53.2%)
Homozygous b-thalassemia 15 (4.8%)
Hemoglobin H 130 (42%)
Age at onset of anemia (years) 3.61 (2.6)
(n = 270)
Age at first transfusion (years) 3.91 (2.8)
(n = 191)
Receiving a blood transfusion during the previous 3 months
(n = 245)
Yes 103 (42%)
No 142 (58%)
Frequency of blood transfusion
(n = 312)
None 146 (46.8%)
Occasional (1-5 times/year) 58 (18.6%)
Low (6-12 times/year) 77 (24.7%)
High (13-22 times/year) 31 (9.9%)
Pre-transfusion Hb level 3 months prior to QOL assessment (g/dL) 8.04 (1.2)
(n = 265)
Serum ferritin level (ng/mL) (n = 127) 2509.9(1903.6)
Iron chelation treatment (n = 314)*
Yes 86 (27.4%)
No 228 (72.6%)
Complications (n = 314)
Yes 19 (6.1%)
No 295 (93.9%)
Age at onset of anemia <2 and age at first transfusion <4 years old
(n = 241)
Yes 75 (31.1%)
No 166 (68.9%)
Having a severe condition** (n = 314)
Yes 113 (36%)
No 201 (64%)
* Subcutaneous injection treatment
** Patients whose age at onset <2 and age at first transfusion <4 years, and/or patients diagnosed with homozygous beta-thalassemia, and/or patients with a
pre-transfusion Hb level lower than 7 g/dL.

Study instruments period (the standard recall period is the past month).
In this study, quality of life assessment was performed Item responses are measured on a five-point rating scale
using the Pediatric Quality of Life Inventory™ (PedsQL™) ranging from 0 (never a problem) to 4 (almost always a
4.0 Generic Core Scale (Thai version). A user agreement problem). The 23 items consist of 8 items on physical
was signed with the MAPI research Institute, Lyon, functioning, 5 items on emotional functioning, 5 items
France, prior to use of the questionnaire. The PedsQL on social functioning and 5 items on school functioning,
4.0 Generic Core Scale includes parallel child self- yielding a total score and two summary scores (i.e., Phy-
reports (age ranges 5-7, 8-12 and 13-18 years) and par- sical Health and Psychosocial Health). Each scale has a
ent proxy-reports (age ranges 2-4, 5-7, 8-12 and 13-18 score ranging from 0-100, the higher score indicating
years). PedsQL items ask how much of a problem a par- higher QOL. The original version of PedsQL has
ticular thing has been for patients during a certain demonstrated good internal consistency and validity in
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large samples of children with acute and chronic health mortality [15], for data analysis serum ferritin level was
conditions, as well as in samples of healthy children and classified into two levels: ≤2,500 ng/mL and > 2,500 ng/
adolescents [24-26]. Furthermore, previous use of the mL. With respect to pre-transfusion Hb level, pre-trans-
PedsQL 4.0 Generic Core Scale (Thai version) in Thai- fusion Hb of less than 7 g/dL indicates a need for regu-
land indicated that it could distinguish between normal lar blood transfusions. Also, pre-transfusion Hb level
children and those with attention-deficit hyperactivity should be monitored routinely to maintain an optimal
disorder (ADHD) [27]. level of 9-10.5 g/dL [15,29]. As a result, in this study,
Apart from the PedsQL questionnaire, the other instru- pre-transfusion Hb was classified into three levels (i.e.,
ment used in this study was a clinical record form. This <7 g/dL, 7-9 g/dL, and >9 g/Dl), In the classification of
form consisted of questions concerning demographics of severity, the criteria used to determine severity in this
the patients (e.g., gender, age, type of payment, hospital study were pre-transfusion hemoglobin level, age at
name, etc.), and clinical information (e.g., onset of ane- onset of anemia and age at first transfusion, and type of
mia, diagnosis, age at first transfusion, history of blood diagnosis. Since there was no consensus on classification
transfusion, hemoglobin (Hb) level, complications, serum of severity among thalassemia patients, for this study,
ferritin level, iron chelation treatment, etc.). the patient was classified as having a severe condition if
any of the following applied: 1) his/her age at onset of
Data collection anemia was less than 2 years, and age at first transfusion
All eligible patients and their parents were approached was less than 4 years; 2) a pre-transfusion hemoglobin
as they came in for routine follow-ups at the thalassemia level <7 g/dL; or 3) having been diagnosed with homo-
clinic in the Department of Pediatrics of each hospital zygous b-thalassemia (thalassemia major). Age at onset
during the data collection period. Written parental of anemia and age at first transfusion was used as one
informed consent and the child’s assent were obtained of the criteria, since a previous study [30] found it to be
prior to participating in the study. At the beginning of an important factor in predicting severity among thalas-
the interview, all respondents were informed of the semia patients. In addition, Hb level was also used to
objectives of the study and were assured that all classify severity of thalassemia in previous study [30].
responses would remain confidential. For HRQOL Similarly, patient with homozygous b-thalassemia (tha-
assessment, the PedsQL questionnaires were to be com- lassemia major) was also classified as severe thalassemia
pleted independently by children with a minimum age as they required chronic blood transfusion.
of 8 years. Children aged 5-7 years were interviewed by
trained interviewers. A clinical record form was then Results
completed via medical record review for all patients in Demographic and clinical characteristic of the 315 tha-
the study. The study was approved by the ethics com- lassemic children and adolescents are presented in
mittee of each participating hospital namely, Institu- Table 2. It was found that about 51% of the participants
tional Review Board of the Royal Thai army of Medical were male. The percentages of patients diagnosed with
Department, Institutional Review Board of the Faculty b-thalassemia/HbE, homozygous b-thalassemia, and
of Medicine, Chulalongkorn University, and Institutional Hemoglobin H were about 53%, 5% and 42%, respec-
Review Board of Saraburi hospital. tively. The mean age (SD) of the patients was 10 (3.3)
years. About 42% of the patients had received a blood
Data analysis transfusion during the three months prior to the inter-
Data were analyzed by Microsoft Excel 2003 and SPSS view, while only 27% of them had received iron chela-
(Statistical Package for the Social Sciences) program ver- tion therapy. Mean pre-transfusion Hb level (SD)
sion 13.0. General characteristics of the patients were measured three months prior to the HRQOL assessment
presented in terms of percentage, mean, and standard was approximately 8.04 (1.2) g/dL, while mean serum
deviation. For HRQOL, both total HRQOL score and ferritin level (SD) was approximately 2,510 (1,903) ng/
summary scores were presented in terms of mean and mL. Only 6% of the patients reported having complica-
standard deviation. Pearson’s correlation, chi-square, tions. Approximately 36% of the patients were classified
ANOVA, and T-test were used to examine the relation- as having a severe condition, as defined above.
ship between HRQOL and each demographic/clinical HRQOL scores based on child self-reports are pre-
factor. Nonparametric tests were used if data were not sented in Table 3. Mean (SD) of the total summary
normally distributed. Factors influencing the quality of score was 76.67 (11.40). When looking at the two sum-
life of children with thalassemia were later examined by mary scores, it was found that the means (SD) of the
multiple regression analysis. Physical Health summary score and Psychosocial Health
Since a serum ferritin level above 2,500 ng/mL is asso- summary score were 78.24 (14.77) and 75.54 (12.76),
ciated with cardiovascular disease [15,16,28] and respectively. For the subscales of Psychosocial Health,
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Table 3 Quality of life scores of child self-report years had significantly low total summary scores. With
Scale Child self-report (n = 315) regard to severity, it was found that the patients who
Mean ± SD were classified as having a severe condition had signifi-
Total summary score 76.67 ± 11.40 cantly low total summary score than their non-severe
Physical health 78.24 ± 14.77 counterparts. On the other hand, diagnosis, complica-
Psychosocial health 75.54 ± 12.76 tion, and serum ferritin level were not associated with
Emotional functioning 75.90 ± 16.62 HRQOL scores.
Social functioning 83.71 ± 14.73 For treatment characteristics, receiving a blood trans-
School functioning 67.89 ± 15.92 fusion during the previous three months was signifi-
cantly associated with the total summary score, as
shown in table 6. The study indicated that patients who
the study revealed that school functioning scored the had received a blood transfusion during the three
lowest (mean = 67.89; SD = 15.92), followed by emo- months prior to HRQOL assessment had significantly
tional functioning (mean = 75.90; SD = 16.62) and social lower total summary scores, as compared to those who
functioning (mean = 83.71; SD = 14.73). did not receive a blood transfusion. On the other hand,
Table 4, 5, and 6 present HRQOL scores from the frequency of blood transfusion was not associated with
child self-report, classified by demographic, clinical, and HRQOL scores.
treatment characteristics of the patients, respectively. As When looking at each summary score, it was found
shown in table 4, age was found to be significantly asso- that two factors - age at onset of anemia and age at first
ciated with total summary score. The findings indicated transfusion, and receiving a blood transfusion during the
that older patients were more likely to have significantly previous three months - were significantly related to the
higher HRQOL compared to their younger counterparts. Physical Health summary score; while age and pre-trans-
As displayed in table 4, the means of the HRQOL total fusion Hb level were significantly related to the Psycho-
summary scores (SD) for children aged 5-7, 8-12 and social Health summary score. For the social and school
13-18 years old were 73.91 (11.79), 75.51 (11.34) and functioning subscales, age, pre-transfusion Hb level, age
80.22 (10.44), respectively. On the other hand, gender at onset of anemia and age at first transfusion, and
was not associated with HRQOL scores. severity were significant predictors of HRQOL. In addi-
Regarding clinical characteristics, having severe condi- tion, iron chelation treatment was significantly asso-
tion, pre-transfusion Hb level, age at onset of anemia ciated with impaired HRQOL in the school functioning
and age at first transfusion were found to be significant subscale.
predictors of total summary scores, as indicated in table Relationships between HRQOL score and patient
5. The study revealed that patients whose Hb level was characteristics were presented in Table 7, in terms of
higher than 9 g/dL had significantly higher total sum- Pearson’s correlation coefficient. Similar to what is
mary score (mean = 79.82; SD = 10.21) than those with shown in Table 4, 5, and 6, it was found that age and
Hb levels of 7-9 g/dL (mean = 75.59; SD = 11.09) or pre-transfusion Hb level were significant predictors of
less than 7 g/dL (mean = 73.51; SD = 13.06). In addi- HRQOL, while serum ferritin level was not.
tion, It was found that patients whose age at onset of Table 8 presents the results of multivariate regression
anemia was <2 years and age at first transfusion <4 analysis in examining factors associated with the total

Table 4 Quality of life scores of child self-report classified by demographic characteristics

Child self-report
Total summary Physical health Psychosocial Emotional Social School
score health functioning functioning functioning
Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD)
Age: years (n = 315)
5-7 n = 63 73.91(11.79) 74.80(16.57) 73.44(13.09) 73.17(19.24) 82.06(17.15) 65.08(16.35)
8-12 n = 153 75.51(11.34) 77.81(14.82) 74.17(12.57) 75.03(16.36) 81.70(14.77) 66.11(16.41)
13-18 n = 99 80.22(10.44) 81.09(12.96) 78.99(12.26) 78.99(16.36) 87.88(12.04) 72.42(13.97)
P-value 0.001 0.054 0.003 0.138 0.003 0.003
Gender (n = 314)
Male n = 159 78.87(11.31) 78.79(14.77) 75.86(11.15) 77.42(15.54) 83.58(13.63) 66.51(16.71)
Female n = 155 76.42(11.54) 77.64(14.83) 75.11(14.24) 74.26(17.58) 83.81(15.85) 69.26(15.05)
P-value 0.701 0.460 0.760 0.101 0.434 0.108
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Table 5 Quality of life scores of child self-report classified by clinical characteristics of the patients
Child self-report
Total summary Physical Psychosocial Emotional Social School
score health health functioning functioning functioning
Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD)
Diagnosis (n = 310)
b-thalassemia n = 165 76.23(11.99) 77.46(13.20) 74.74(13.20) 76.03(17.36) 83.60(15.57) 67.06(14.92)
Homozygous b- n = 15 71.81(10.83) 73.54(13.91) 71.89(12.89) 70.00(16.58) 80.00(13.70) 62.67(15.68)
thalassemia
Hb H n = 130 77.54(10.72) 79.49(14.68) 76.63(12.28) 76.23(15.76) 84.04(13.67) 69.23(17.19)
P-value 0.145 0.187 0.234 0.368 0.424 0.103
Age at onset of anemia <2 and age at first transfusion <4 years old (n = 241)
Yes n = 75 72.75(11.33) 73.96(15.95) 73.51(12.64) 74.53(14.71) 78.53(17.10) 63.26(14.94)
No n = 166 77.72(11.08) 79.01(14.67) 76.02(12.73) 76.08(15.99) 85.49(13.45) 69.52(16.15)
P-value 0.002 0.023 0.099 0.228 0.003 0.003
Complications (n = 314)
Yes n = 19 77.52(14.37) 77.14(19.05) 77.81(16.21) 76.32(19.57) 84.21(16.52) 72.63(15.13)
No n = 295 76.60(11.22) 78.30(14.50) 75.34(12.52) 75.83(16.46) 83.66(14.66) 67.56(15.97)
P-value 0.773 0.941 0.169 0.628 0.661 0.228
Having a severe condition* (n = 314)
Yes n = 113 74.07(12.05) 75.97(15.93) 74.12(12.77) 75.53(15.27) 78.89(16.86) 63.73(16.98)
No n = 201 78.10(10.79) 79.49(15.93) 76.26(12.71) 76.04(17.37) 86.39(12.68) 69.63(15.09)
P-value 0.004 0.077 0.097 0.417 <0.001 0.021
Serum ferritin level (n = 127)
<2500 ng/mL n = 79 76.50(12.83) 78.20(15.66) 75.25(13.38) 74.18(18.70) 84.24(15.19) 66.27(14.82)
>2500 ng/mL n = 48 76.61(10.14) 76.88(13.03) 75.76(12.73) 80.42(14.39) 84.06(13.94) 64.89(15.38)
P-value 0.0897 0.426 0.903 0.100 0.726 0.741
Pre-transfusion Hb level 3 months prior to QOL assessment (n = 265)
<7 g/dL n = 49 73.51(13.06) 75.06(17.84) 73.82(13.41) 74.03(14.21) 76.84(16.64) 64.90(18.78)
7-9 g/dL n = 159 75.59(11.09) 77.10(14.61) 73.78(13.21) 87.01(13.09) 84.03(14.08) 66.00(15.55)
>9 g/Dl n = 57 79.82(10.21) 81.03(13.35) 79.18(17.44) 76.49(17.44) 87.01(13.09) 74.03(14.21)
P-value 0.012 0.163 0.016 0.474 0.002 0.008
* Patients whose age at onset <2 and age at first transfusion <4 years, and/or patients diagnosed with homozygous b-thalassemia, and/or patients with
a pre-transfusion Hb level lower than 7 g/dL

summary score. It was shown that age and severity were study [11], the school functioning subscale scored the
significant predictors of HRQOL (i.e., total summary lowest. This could be explained by the fact that frequent
score). The findings revealed a positive relationship absenteeism from school for hospital visits, and a lack of
between age and HRQOL (b = 0.243, p < 0.001). Simi- energy when performing academic activities, had a sig-
larly, a significant relationship was also found between nificant negative impact on the children’s HRQOL
severity and HRQOL (b = -0.162, p = 0.003). [11,31-33].
Although the pattern of HRQOL scores was found to
Discussion be the same as in a previous study [11], HRQOL scores
Since the focus of this study was on patient perspective obtained from this study were somewhat higher. Based
then only HRQOL scores obtained from child self- on the previous study[11], the mean total summary
report were examined. While data on parent proxy- score (SD), mean Physical health summary score (SD),
report were also collected they will be the focus of sub- and mean Psychosocial health summary score (SD) were
sequent manuscript and will be available upon request. 67.70 (12.40), 69.17 (15.34), and 67.39 (13.24), respec-
Similar to what was found in a previous study [11], tively. However, due to the absence of HRQOL scores
the assessment of HRQOL of thalassemia patients in of healthy children in Thailand as well as differences in
this study showed that psychosocial health had a lower country-specific characteristics, direct comparisons
score than physical health. Also, as with the previous could be made with caution. Nevertheless, possible
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Table 6 Quality of life scores of child self-report classified by treatment characteristics of the patients
Child self-report
Total summary Physical Psychosocial Emotional Social School
score health health functioning functioning functioning
Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD)
Receiving a blood transfusion during the previous 3 months (n = 245)
Yes n = 103 74.49(12.58) 75.00(16.19) 74.54(13.12) 74.85(18.37) 82.67(16.04) 65.15(16.90)
No n = 142 78.51(10.55) 80.74(13.07) 76.84(12.53) 76.79(16.10) 85.35(13.18) 69.82(15.47)
P-value 0.027 0.008 0.187 0.615 0.320 0.079
Frequency of blood transfusion (n = 312)
None n = 146 78.05(10.77) 79.77(13.25) 76.76(12.53) 76.30(16.61) 85.68(13.55) 69.42(16.92)
Occasional n = 58 76.52(10.86) 78.50(15.77) 74.37(12.40) 74.91(15.55) 82.33(15.59) 69.14(13.48)
Low n = 77 75.06(11.97) 76.70(15.52) 74.13(13.78) 75.71(17.69) 81.16(15.47) 65.65(15.65)
High n = 31 76.44(12.38) 76.91(16.00) 76.45(17.33) 76.45(17.33) 85.65(13.84) 66.45(14.21)
P-value 0.42 0.62 0.45 0.72 0.13 0.26
Iron chelation treatment* (n = 277)
Yes n = 61 74.39(12.24) 74.59(15.01) 76.64(13.75) 76.64(17.79) 82.62(15.04) 63.61(17.06)
No n = 216 77.01(11.11) 78.73(14.85) 75.64(12.27) 75.21(16.34) 83.84(14.61) 69.21(15.67)
P-value 0.214 0.051 0.759 0.343 0.601 0.026
*subcutaneous injection treatment

reason that could account for the difference in HRQOL mentioned earlier - that pre-transfusion Hb level should
scores between the two studies was that the patients in be monitored routinely to maintain an optimal level of
this study represented milder cases of thalassemia, as 9-10.5 g/dL [15,29] - the findings of this study indicated
compared to those in the previous study [11]. About that patients with a pre-transfusion Hb level >9 g/dL
60% of patients in the previous study were diagnosed had significantly higher HRQOL than patients whose
with homozygous b-thalassemia, and 77% were transfu- pre-transfusion Hb level was <9 g/dL. In the case of
sion-dependent. In contrast, only 4.8% of the patients in blood transfusion, one possible explanation for the sig-
this study were diagnosed with homozygous b-thalasse- nificant relationship between receiving a blood transfu-
mia, and only 42% had received a blood transfusion dur- sion and lower HRQOL is that patients who received
ing the previous three months. blood transfusions during the three months prior to
Consistent with the findings from several studies con- HRQOL assessment were those with low pre-transfusion
ducted on other diseases [34-37], this study found that Hb levels. In contrast, this study found no significant
pre-transfusion Hb level and receiving a blood transfu- relationship between frequency of blood transfusion per
sion during the three months prior to HRQOL assess- year and HRQOL. This non-significant relationship
ment were significant predictors of HRQOL among could be due to the fact that the questions used to
thalassemia patients. This could be explained by the fact assess HRQOL of the patients were related to the feel-
that lower Hb level is associated with a number of ings and conditions of the patients during the previous
symptoms, such as fatigue, general weakness, and month; therefore the number of transfusions per year
decreased mental alertness, which might lead to might not be relevant to the HRQOL score.
impaired HRQOL of the patients in several domains. Consistent with a previous study [11], age was a sig-
Similar to the recommendation for blood transfusion nificant predictor of HRQOL among thalassemia

Table 7 Relationship between quality of life scores and patient characteristics by Pearson’s correlation coefficient
Pearson’s correlation coefficient
Total summary Physical Psychosocial Emotional Social School
score health health functioning functioning functioning
Serum ferritin level (ng/ -0.061 -0.091 -0.052 0.444 -0.043 -0.088
mL)
Pre-transfusion Hb level 0.170* 0.105 0.123** 0.009 0.222* 0.184*
(g/dL)
Age (years) 0.250* 0.163* 0.185* 0.175* 0.217* 0.198*
Thavorncharoensap et al. BMC Blood Disorders 2010, 10:1 Page 8 of 10
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Table 8 Multivariate regression analysis results might limit the extent to which the results could be
b SE (b) P-value extrapolated to patients in other settings. In addition,
Constant 4.231 0.028 <0.001 failure to recruit adequate subjects, as stated in sample
Having a severe condition* -0.162 0.017 0.003 size calculation may be a potential limitation of the
Age (years) 0.243 0.003 <0.001 study. Lastly, as there was no consensus on how to
determine severity of thalassemia patient, the criteria to
R2 = 0.089, Y = Ln (total summary score)
* Patients whose age at onset <2 and age at first transfusion <4 years, and/or assess severity of thalassemia varied across studies, ran-
patients diagnosed with homozygous b-thalassemia, and/or patients with a ging from only referred to patients with homozygous b
pre-transfusion Hb level < 7 g/dL.
thalassemia [39] to other different criteria [30,40,41]. As
the result, the direct comparison across studies should
patients. Although transitioning from adolescence to be made with caution. The definition of severity used in
adulthood presents many new challenges - a more inde- this study was developed based on local expert opinions.
pendent lifestyle, choosing a successful career path, and As only data on type of diagnosis, hemoglobin level, age
marriage [32] - this study found that adolescent patients onset of anemia, and age at first transfusion were
had significantly higher HRQOL than their younger required to assess severity, this definition seemed to be
counterparts. This finding was similar to that of a pre- feasible in less developed countries, where data on
vious study which revealed that older children with tha- laboratory value or genetic information were unavailable
lassemia experienced fewer symptoms of depression, in general practice.
reflecting a process of adjustment and coping [6].
Although existing evidence indicates that long-term Conclusion
iron overload might result in severe morbidity and mor- The findings of this study highlight the significant nega-
tality [15,16,28,38], and that a serum ferritin level higher tive impact of thalassemia and its treatment on HRQOL
than 2,500 ng/dL is associated with cardiac complica- in terms of physical functioning and psychosocial func-
tions and mortality [15], this study found no relation- tioning, especially in the school functioning subscale. In
ship between serum ferritin level and HRQOL. This light of this, and considering the prevalence of thalasse-
contradictory result could possibly be due to the fact mia in Thailand, our study suggested that modification
that damaging, long-term iron overload occurs gradu- of existing thalassemia management could be beneficial.
ally; so short-term iron overload, as represented by an Psychosocial and counseling programs aimed at helping
elevated serum ferritin level, did not cause significant patients discuss and accept their illness, facilitating a
visible symptoms or complications, and hence had no normal lifestyle, and providing a link between patients,
impact on their HRQOL. Similar to the findings of pre- school officials, the family and the physician may be
vious studies [13,14], this study found that, due to the helpful in alleviating these difficulties, especially aca-
burden of nightly subcutaneous injections of desferriox- demic performance. In addition, modification of health
amine 5 to 7 days per week [29], iron chelation treat- care services for children with thalassemia to become
ment was significantly related to impaired HRQOL. more patient-centered, flexible and comprehensive may
Complications and type of diagnosis were not related reduce time spent at hospitals and also improve treat-
to HRQOL level in this study. This could be because ment outcomes, including HRQOL of the patients.
the number of patients having complications was too In the meantime, while stem cell transplantation is not
small (only 6.1%) to detect a significant difference. Simi- considered as a standard treatment, blood transfusion
larly, although patients diagnosed with homozygous b- and iron chelation therapy are required for thalassemia
thalassemia were expected to have significantly lower patients. The findings of this study confirmed the
HRQOL since they were transfusion-dependent, a non- importance of maintaining pre-transfusion Hb level
significant relationship between type of diagnosis and above 9 g/dL. Therefore, effective strategies aimed at
HRQOL was found in this study. This could possibly be promoting access to blood transfusions should be
due to the small number of patients diagnosed with employed in several developing countries, where at pre-
homozygous b-thalassemia (< 5%) that were included in sent there is limited access to this essential treatment.
this study. Concordant with the findings from a previous In addition, given the fact that long-term iron overload
study conducted on children with thalassemia [11], gen- leads to severe complications and increase mortality, a
der was not associated with HRQOL in this study. more convenient regimen of iron chelation that would
One limitation of this study, as previously mentioned, prevent the long-term consequences of iron overload is
is the absence of HRQOL scores of healthy children in essential and could help improve HRQOL of the patient
Thailand. As a result, the true magnitude of thalasse- [40-42], even in the situation where no significant rela-
mia’s impact on HRQOL was hardly estimated. Other tionship between the elevation of serum ferritin and
limitation is that purposive sampling of the settings HRQOL is found.
Thavorncharoensap et al. BMC Blood Disorders 2010, 10:1 Page 9 of 10
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This study has been supported by a grant from the National Research
Vecchio GC, Romeo MA, Forni GL, Gamberini MR, Ghilardi F, Piga A,
Council of Thailand via the Clinical Research Collaboration Network (CRCN),
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Author details
1 death in thalassaemia major. Lancet 1989, 2:27-30.
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok,
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Bangkok, Thailand. 3Department of Pediatrics, Faculty of Medicine,
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Chulalongkorn University, Bangkok, Thailand. 4Faculty of Economics,
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Chulalongkorn University, Bangkok, Thailand. 5Department of Pediatrics,
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Authors’ contributions
predictor of pediatric healthcare costs: a two-year prospective cohort
MT was involved in the study design; data collection, interpretation and
analysis. Health and Quality of Life Outcomes 2004, 2:48.
analysis; and drafting the manuscript. KT, NI, AR were involved in the study
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intellectual content. BU was involved in the study design and data
24. Varni JW, Seid M, Knight TS, Uzark K, Szer IS: The PedsQL 4.0 generic core
collection, and in revising the paper for important intellectual content. KI
scales: sensitivity, responsiveness, and impact on clinical decision-
was involved in the study design and in revising the paper for important
making. J Behav Med 2002, 25:175-193.
intellectual content. All authors read and approved the final manuscript.
25. Varni JW, Seid M, Kurtin PS: The PedsQL: Measurement model for the
Pediatric Quality of Life Inventory. Med Care 1999, 37:126-139.
Competing interests
26. Varni JW, Seid M, Kurtin PS: PedsQL 4.0: Reliability and validity of the
The authors declare that they have no competing interests.
Pediatric Quality of Life Inventory version 4.0 generic core scales in
healthy and patient populations. Med Care 2001, 39:800-812.
Received: 21 September 2009
27. Pongwilairat K, Louthrenoo O, Charnsil C, Witoonchart C: Quality of life of
Accepted: 21 January 2010 Published: 21 January 2010
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Cite this article as: Thavorncharoensap et al.: Factors affecting health-
related quality of life in Thai children with thalassemia. BMC Blood
Disorders 2010 10:1.

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