ORIGINALARTICLE

FACTORS AFFECTING ADHERENCE TO IRON CHELATION THERAPY IN THALASSEMIA

MAJOR PATIENTS

Ghazala¹, Kainaat², Ihtisham Ul Haq³, Bibi Asma⁴, Jawairia Gul³, Anhum Khan³

How to cite this article

ABSTRACT

OBJECTIVES

Ghazala, Kainaat, Haq IU, Asma B,

This study aimed to determine the factors aecting adherence to iron

Gul J, Khan A. Factors Affecting

chelation therapy among patients with thalassemia major.

Adherence to Iron Chelation Therapy

METHODOLOGY

In Thalassemia Major Patients. J

Gandhara Med Dent Sci.

This is a cross-sectional analytical study conducted at a tertiary care

hospital. 97 patients with 97 cases of 2 thalassemia major were recruited

using a non-probability, consecutive sampling method. The structured

questionnaire and medical record review were used to collect data.

Compliance was classied as good, moderate, and poor. SPSS version 25

was used to analyze the data. Associations were tested using the chi-square

test, and p-values of 0.05 or less were considered statistically signicant..

RESULTS

2026;13(3):71-75.

https://doi.org/10.37762/jgmds.13-3.910

Date of Submission: 13-04-2026

Date Revised:

Date Acceptance:

16-06-2026

18-06-2026

¹Consultant, Department of Pediatric

Medicine, Bacha Khan Medical

Complex, Swabi

The mean age of participants was 15.6 ± 7.0 years. Good adherence was

observed in 46.4% of patients, while 53.6% showed suboptimal adherence.

No statistically signicant association was found between adherence and

demographic or clinical variables (p > 0.05). The most common reasons for

non-adherence were forgetfulness (28.8%) and painful injections (25.0%),

followed by high cost of therapy (19.2%) and side eects (17.3%).

CONCLUSION

³PostGraduate Resident, Department

of Pediatric Medicine, Bacha Khan

Medical Complex, Swabi

⁴District Specialist, Department of

Pediatric Medicine, Bacha Khan

Medical Complex, Swabi

Adherence to iron chelation therapy is suboptimal among thalassemia

patients and is mainly inuenced by behavioral and treatment-related factors.

Strategies focusing on patient education, adherence support, and simplied

treatment regimens are essential to improve compliance and clinical

outcomes.

KEYWORDS: Thalassemia Major, Iron Chelation Therapy, Adherence,

Ferritin, Compliance, Pakistan

Correspondence

²Kainaat, Senior Registrar, Department

of Pediatric Medicine, Bacha Khan

Medical Complex, Swabi

+92-332-5062649

emelkainaat@gmail.com

INTRODUCTION

One of the

adherence, including complex treatment regimens,

adverse

drug

eects,

high

cost

therapy,

most

widespread

inherited

psychological factors, and lack of patient awareness. In

addition, injectable therapies such as Deferoxamine are

often associated with discomfort and inconvenience,

further contributing to poor compliance.^7,8The lack of

hemoglobinopathies worldwide is thalassemia major,

which is prevalent in South Asia and the Middle East.¹

The majority of patients with β-thalassemia cannot

survive without regular blood transfusions, which in

turn causes progressive iron overload. An overload of

iron in important body parts like the heart, liver, and

endocrine glands causes serious complications, like

healthcare

facilities,

nancial

limitations,

and

insucient patient education in low and middle-income

countries such as Pakistan only exacerbate this in these

countries. Even though numerous international studies

have examined adherence patterns, little local

information is available on the factors that specically

affect adherence in patients with thalassemia in this

area. Therefore, this study was conducted to assess

adherence to iron chelation therapy and identify key

factors aecting compliance among patients with

thalassemia major.

cardiomyopathy,

liver

cirrhosis,

and

endocrine

dysfunction, posing a signicant risk to morbidity and

mortality.^2,3Iron chelation therapy is important in

preventing iron overload and enhancing survival in such

patients.⁴

Existing

chelating

agents

such

Deferoxamine, Deferiprone, and Deferasirox have

proven eective in lowering serum ferritin levels and

iron load. Despite these treatment improvements,

compliance with iron chelation therapy remains a major

challenge, especially in resource-constrained settings.⁵

Non-adherence to chelation therapy has been widely

METHODOLOGY

This cross-sectional analytical study assessed factors

affecting adherence to iron chelation therapy among

patients with thalassemia major. The study was

conducted at the Thalassemia Care Unit of a tertiary

reported and is associated with poor clinical outcomes

increased risk of complications, and reduced quality of

life.⁶Several factors have been implicated in poor

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J Gandhara Med Dent Sci

Factors Aecting Adherence to Iron Chelation Therapy in Thalassemia

care hospital over 6 months, from May 2022 to SPSS Statistics version 25 was used to enter the data

November 2022. Ethical approval for the study was and analyze it. The mean and standard deviation of

obtained from the Research Evaluation Unit, College of quantitative variables, such as age and serum ferritin

Physicians and Surgeons Pakistan (CPSP) prior to data levels, were provided; the mean and percentage

collection (Ref No: CPSP/REU/PED-2020-022-6040; frequencies of qualitative variables were provided. The

chi-square test was used to determine the relationship

dated May 21, 2022). Written informed consent was

obtained from all participants, and in the case of between

adherence

and

independent

variables,

including gender, socioeconomic status, type of

chelation therapy, side eects, and level of knowledge.

pediatric patients, consent was obtained from their

parents or legal guardians. Condentiality and

anonymity of patient information were strictly Cramer's V was used to determine the strength of

maintained throughout the study. The sample size for association.

p-value

≤

0.05 was considered

this study was calculated using the World Health statistically signicant.

Organization (WHO) formula for estimating

proportion, considering adherence to iron chelation RESULTS

therapy as the primary outcome variable. A condence

level of 95% was used, corresponding to a Z value of A total of 97 patients with thalassemia major were

1.96. Because adherence to iron chelation therapy included in the study. The mean age of participants was

varies across studies, an expected proportion (p) of 50% 15.6 ± 7.0 years (range: 4-28 years). The majority of

was assumed to ensure a maximum sample size.⁹The patients belonged to the 10–18 years age group

(40.2%), followed by >18 years (36.1%) and <10 years

margin of error (d) was set at 10%. Based on these

parameters, the calculated sample size was 96 (23.7%). A slight female predominance was observed

participants. To ensure adequacy and account for (56.7%). Most participants were from urban areas

potential data inconsistencies, 97 patients were included (51.5%), while 45.4% had low socioeconomic status,

in the study. The sampling method used was a non- indicating a considerable burden on lower-income

groups. The clinical prole showed that most patients

had a longer disease duration, with 36.1% each in the 5-

probability, consecutive sampling method, in which

patients who presented to the thalassemia center during

the study period were recruited. The patients were 10 years and >10 years categories. A majority of

eligible if they were 4 years of age or older, had a patients (72.2%) required ≥2 blood transfusions per

confirmed diagnosis of β-thalassemia major, had been month, indicating severe disease burden. Regarding

on iron chelation treatment for at least 6 months, and treatment, Deferiprone (40.2%) and Deferoxamine

(38.1%) were more commonly used compared to

Deferasirox (21.6%). Slightly more than half of the

were willing to take part in the study. Patients with

other hemoglobinopathies not under chelation therapy,

with severe comorbid conditions that may hinder patients (53.6%) had been on chelation therapy for less

adherence assessment, and with incomplete medical than 2 years. The mean serum ferritin level was 3343.8

records were excluded.

structured, pre-tested ± 1053.0 ng/mL (range: 1604-4984 ng/mL), reecting

questionnaire was used to collect data, and medical significant iron overload among the study population.

Assessment of adherence to iron chelation therapy

records were reviewed. Demographic variables (age,

gender, residence, socioeconomic status), clinical showed that fewer than half of patients demonstrated

(duration of disease, frequency of blood transfusions, optimal adherence. A total of 46.4% of patients showed

serum ferritin levels), and treatment-related variables good adherence, while 26.8% each had moderate and

(type and duration of chelation therapy) were collected poor adherence. Overall, 53.6% of patients exhibited

in the questionnaire. The adherence to iron chelation suboptimal adherence (moderate + poor), indicating a

significant gap in eective disease management. The

therapy was evaluated using patient responses and

classified as good, moderate, or poor. Other factors relationship between demographic and clinical factors

such as side eects, level of knowledge, and non- and adherence to iron chelation therapy was evaluated

adherence causes were also recorded. Face-to-face with the Chi-square test. No signicant association was

interviews were conducted during regular hospital visits found between adherence and gender, socioeconomic

status, type of chelation therapy, side eects, or

knowledge level (p > 0.05). Eect sizes were weak

to collect the data. Hospital records and clinical data,

such as serum ferritin levels and treatment history, were

confirmed to achieve accuracy and reduce recall bias. because the variables were associated with small eect

The questionnaire was pre-tested by hematology and sizes. Among patients with suboptimal adherence

medical education experts to ensure validity. A pilot (moderate and poor), the most common reason for non-

study comprising about 10% of the sample was adherence was forgetfulness (28.8%), followed by

painful

injections

(25.0%).

Other

important

conducted to assess the instrument's clarity, feasibility,

and reliability, and required changes were made. IBM

contributing factors included high cost of therapy

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Factors Aecting Adherence to Iron Chelation Therapy in Thalassemia

Table 4: Association of Factors with Adherence to Iron Chelation

(19.2%) and side eects (17.3%), while lack of

awareness (9.6%) was the least reported reason.

Therapy (n = 97)

Variable Category Good Modera Poor χ²

p-va Cramer’s

n(%) te n (%) n(%) value lue

Table 1: Demographic Characteristics of Participants (n = 97)

Male

22(52. 07(16.7 13(31. 3.8880.143 0.20

4%) %) 0%)

Female 23(41. 19(34.5 13(23.

Variable

Category

<5 years

5-10 years

>10 years

<2/month

≥2/month

Frequency (%)

27 (27.8%)

35 (36.1%)

27 (27.8%)

70 (72.2%)

Present 19(51. 08(21.6 10(27. 0.918 0.63 0.09

4%) %)

Absent 26(43. 18(30.0 16(26.

3%) %) 7%)

19(47. 10(25.0 11(27. 0.113 0.94 0.03

5%) %) 5%)

26(45. 16(28.1 15(26.

6%) %) 3%)

0%)

Side

Eects

Good

Poor

Blood Transfusion

Frequency

Knowledge

Level

Type of Chelation

Therapy

Deferasirox 21 (21.6%)

Deferiprone 39 (40.2%)

Deferoxamine 37 (38.1%)

Duration of

Chelation Therapy

Serum Ferritin (ng/mL) -

<2 years

≥2 years

52 (53.6%)

45 (46.4%)

3343.8 ± 1053.0

Table 5: Reasons for Non-Adherence (n = 52)

Frequency (%)

Reason

Forgetfulness

(1604-4984)

15 (28.8%)

13 (25.0%)

10 (19.2%)

09 (17.3%)

05 (9.6%)

Painful injections

High cost of therapy

Side eects

Table 3: Adherence to Iron Chelation Therapy (n = 97)

Adherence Level

Good Adherence

Moderate Adherence

Poor Adherence

Frequency (%)

45 (46.4%)

26 (26.8%)

Lack of awareness

DISCUSSION

26 (26.8%)

The present study evaluated adherence to iron chelation

therapy among patients with thalassemia major and

identified factors inuencing compliance. The ndings

revealed that only 46.4% of patients demonstrated good

adherence,

while

53.6%

exhibited

suboptimal

adherence, highlighting a signicant gap in eective

disease management. These ndings are consistent with

recent international literature, which indicates that

adherence rates among thalassemia patients remain

suboptimal, typically ranging from 40–60% depending

on healthcare access and treatment modalities.^10,11The

study's demographic prole was dominated by

adolescents (10-18 years), a crucial age group for

adherence issues. The results of the studies by

Musallam et al. (2025) and Lee Wan et al. (2023)

demonstrated that adolescents tend to be less adherent

to treatment due to psychosocial factors, caregiver

treatment fatigue, and reliance.^12,13Similarly, the slight

female predominance observed in this study aligns with

regional data; however, no signicant association

between gender and adherence was found, which is

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Factors Aecting Adherence to Iron Chelation Therapy in Thalassemia

consistent with ndings from a multicenter study demographic or clinical variables. The lack of robust

conducted in the Middle East.¹⁴The clinical statistical

correlations

indicates

that

treatment

characteristics revealed that a large proportion of adherence is a multifactorial and complex problem that

patients required frequent transfusions (≥2/month) and needs extensive interventions such as patient

had elevated serum ferritin levels, indicating signicant

iron overload. Despite this, adherence remained

suboptimal. This paradox has also been reported in

recent studies, suggesting that even patients with severe

disease burden fail to adhere adequately to therapy.¹⁵

counseling, simplied treatment regimens, and

psychosocial support.

LIMITATIONS

The mean ferritin level in this study (3343.8 ng/mL) is This study has several limitations. First, it was

comparable to that reported in a Pakistani study by

Khan et al. (2022), in which poor adherence was

associated with greater iron overload.¹⁶In terms of

treatment modalities, Deferiprone and Deferoxamine

were more common than Deferasirox. Even though oral

chelators such as Deferasirox are often associated with

higher adherence due to their ease of use, this study

failed to show a statistically signicant relationship

between chelation therapy type and adherence. Reddy

et al. (2022) have reported similar ndings, indicating

that it depends on factors beyond the type of drug,

conducted at a single tertiary care center with a

relatively small sample size, which may limit the

generalizability of the ndings to the broader

thalassemia population. Second, the cross-sectional

design prevents establishing causal relationships

between identied factors and adherence to iron

chelation therapy. Third, adherence was assessed

primarily through self-reported responses, making the

results susceptible to recall and social desirability bias.

Finally, psychosocial factors such as caregiver support,

mental health status, and health literacy were not

explored in detail and may have inuenced adherence

behaviors.

including

patient

behavior

and

socioeconomic

limitations.

Notably, there were no statistically

signicant dierences in adherence with gender,

socioeconomic status, side eects, or level of

knowledge. Even though socioeconomic status could be

regarded as a key determinant of adherence, the non-

signicant correlation in this study might be explained

by the fact that nancial constraints were relatively

homogenous among the study population. Lee et al.

(2024) also found weak correlations between

socioeconomic variables and compliance, highlighting

the multifactorial nature of compliance behavior.¹⁷The

most fatal results of this research are associated with

the causes of non-adherence, with forgetfulness (28.8)

and painful injections (25.0) as the most common ones.

Recent literature provides strong support for these

findings. Forgetfulness was cited by Locke et al. (2022)

in a systematic review as one of the most frequent

barriers to adherence, especially in pediatric and

adolescent populations.¹⁰Similarly, pain linked to

injectable medications, namely Deferoxamine, has been

recurrently cited as a signicant discouraging factor.¹⁸

The barriers represented by the cost of therapy (19.2%)

indicate the diculties in the low- and middle-income

countries such as Pakistan. South Asian research has

also emphasized that nancial strain has a major impact

on long-term adherence to treatment, particularly in

chronic illnesses that require lifelong treatment (19,20).

Even though the least reported factor in this study was

lack of awareness, its presence still suggests the need to

establish structured patient education programs.

Overall, the results of this research support the idea that

the behavioral and treatment-related factors contribute

more to adherence to iron chelation therapy than the

CONCLUSIONS

Adherence to iron chelation therapy among patients

with thalassemia major was found to be suboptimal,

with more than half of the patients demonstrating

moderate to poor adherence. The study highlights that

adherence is primarily inuenced by behavioral and

treatment-related factors rather than demographic or

clinical characteristics. Forgetfulness and painful

administration methods emerged as the leading barriers,

followed by nancial constraints and treatment-related

side eects. These ndings emphasize the need for

targeted interventions, including patient education,

adherence support strategies, and the promotion of

more convenient treatment options, to improve long-

term compliance and reduce complications associated

with iron overload.

CONFLICT OF INTEREST: None

FUNDING SOURCES: None

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AUTHORS CONTRIBUTION

Ghazala Concept Design; Data Acquisition; Data

Analysis/interpretation; Drafting Manuscript; Critical

Revision; Supervision; Final; Approval

Musallam KM, Cappellini MD, Porter JB, Farmakis D,

Eleftheriou A, Angastiniotis M, et al. TIF guidelines for the

Kainaat

Concept

Design; Data Acquisition; Data

Drafting Manuscript; Critical

Analysis/interpretation;

Revision; Final; Approval

management

transfusion-dependent

β-thalassemia.

HemaSphere.

2025;9(3):e70095.

Ihtisham Ul Haq - Concept & Design; Data Acquisition;

Drafting Manuscript; Critical Revision; Final; Approval

Bibi Asma - Concept & Design; Data Acquisition; Drafting

Manuscript; Critical Revision; Final; Approval

https://doi.org/10.1097/HS9.0000000000007095.

12.

13.

14.

Lee Wan J, Nurul Ain Mohd T, Farida I, Li SC. Adherence

and health-related quality of life of transfusion-dependent

thalassemia patients. Arch Pharm Pract. 2023;14(4):89-95.

Kanwal M, Raza S. Predictors of non-adherence to iron

Jawairia Gul - Concept & Design; Data Acquisition; Drafting

Manuscript; Critical Revision; Final; Approval

chelation therapy in pediatric thalassemia patients.

Rawalpindi Med Coll. 2022;26(Suppl 1):73-78.

Anhum Khan - Concept & Design; Data Acquisition; Drafting

Manuscript; Critical Revision; Final; Approval

Chawsamtong S, Jetsrisuparb A, Kengkla K, Jaisue S. Eect

of drug use calendar on adherence to iron chelation therapy in

young thalassemia patients. Pharm Pract (Granada).

2022;20(1):2570.

The authors accept responsibility for all aspects of the work

and will ensure that any concerns regarding the accuracy or

integrity of any part are properly investigated and resolved.

https://doi.org/10.18549/PharmPract.2022.1.2570.

35464153.

PMID:

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