Serum ferritin levels, socio-demographic factors and desferrioxamine therapy in multi-transfused thalassemia major patients at a government tertiary care hospital of Karachi, Pakistan
BMC Research Notes
Serum ferritin levels, socio-demographic factors and desferrioxamine therapy in multi-transfused thalassemia major patients at a government tertiary care hospital of Karachi, Pakistan
Haris Riaz 0
Talha Riaz 2
Muhammad Ubaid Khan 0
Sina Aziz 1
Faizan Ullah 0
Anis Rehman 2
Qandeel Zafar 4
Abdul Nafey Kazi 3
0 House officer, Civil Hospital Karachi , Pakistan
1 Associate Professor, Department of Paediatrics, Dow University of Health Sciences , Karachi , Pakistan
2 Medical graduates, Civil Hospital Karachi , Pakistan
3 Medical student, Dow Medical College , Karachi , Pakistan
4 Electives students, Department of Paediatrics, Civil Hospital Karachi, student of King's College , London , UK
Background: Beta thalassemia is the most frequent genetic disorder of haemoglobin synthesis in Pakistan. Recurrent transfusions lead to iron-overload manifested by increased serum Ferritin levels, for which chelation therapy is required. Findings: The study was conducted in the Pediatric Emergency unit of Civil Hospital Karachi after ethical approval by the Institutional Review Board of Dow University of Health Sciences. Seventy nine cases of beta thalassemia major were included after a written consent. The care takers were interviewed for the socio-demographic variables and the use of Desferrioxamine therapy, after which a blood sample was drawn to assess the serum Ferritin level. SPSS 15.0 was employed for data entry and analysis. Of the seventy-nine patients included in the study, 46 (58.2%) were males while 33 (41.8%) were females. The mean age was 10.8 (± 4.5) years with the dominant age group (46.2%) being 10 to 14 years. In 62 (78.8%) cases, the care taker education was below the tenth grade. The mean serum Ferritin level in our study were 4236.5 ng/ ml and showed a directly proportional relationship with age. Desferrioxamine was used by patients in 46 (58.2%) cases with monthly house hold income significant factor to the use of therapy. Conclusions: The mean serum Ferritin levels are approximately ten times higher than the normal recommended levels for normal individuals, with two-fifths of the patients not receiving iron chelation therapy at all. Use of iron chelation therapy and titrating the dose according to the need can significantly lower the iron load reducing the risk of iron-overload related complications leading to a better quality of life and improving survival in Pakistani beta thalassemia major patients. Conflicts of Interest: None
Beta thalassemia major; Ferritin; Desferrioxamine; Socio-demographic factors; Pakistan
Beta thalassemia ranks first amongst the genetic
disorders associated with haemoglobin synthesis in terms of
prevalence and it is the result of an inherited defect in
the synthesis of the beta chain of the adult haemoglobin.
Consequently the erythropoiesis is defective and anemia
is produced [
]. Considering the 5 to 7% carrier rate in
Pakistan, the number of carriers is expected to approach
10 million [
]. This grades thalassemia as one of the
most common inherited disorders in Pakistan [
to lack of appropriate documentation, precise data
pertaining to the incidence and prevalence of the disease
are lacking. However, different studies statistically
estimate that the number of thalassemia major patients
born each year is in the order of 4000 to 9000 [
Due to repeated blood transfusions, all thalassemic
patients require Iron Chelation Therapy (ICT) in order
to reduce the increased iron load that if not eliminated
properly can result in life threatening complications,
including severe cardiac toxicity in the second decade of
life, producing a significant decrease in the total life
expectancy of these patients . However, the practice
of repeated parenteral ICT therapy imposes various
economic burdens in those who cannot afford such a
therapy. Oral chelators such as Deferasirox are much more
expensive than the traditional ICT’s which makes access
difficult for the majority of socio-economically
underprivileged patients [
]. Desferoxamine (DFE), a
parenteral drug used widely as ICT has been employed in the
treatment of beta thalassemia for nearly four decades
and has shown to be effective in reducing the hepatic
and extra-hepatic adverse affects, particularly myocardial
]. However, despite the protracted method of
8- to 10- hours of infusion at least five times a week,
the patients suffering from beta thalassemia are often
not able to achieve the desired threshold of Ferritin
levels in their blood [
]. This study also highlighted the
dismal situation of ICT having a negative impact on
health related quality of life (HRQOL), and that in most
of the cases compliance with ICT being suboptimal,
signifying non-satisfactory provision of chelation therapy
with respect to economic, clinical and quality of life
The aim of the present study is to assess the
sociodemographic factors, serum Ferritin levels and
adherence to iron chelation therapy in multi-transfused
Thalassemia major patients. The series is composed mainly
of Thalassemics children and young patients.
The present study is a continuation of the work on
Thalassemia major patients and is carried out on the same
patients in which the sero-prevalence of viral hepatitis
and HIV was determined, published in the Tropical Dr.
]. However, the objectives are entirely
different from the one published.
This is a descriptive cross-sectional study, conducted
from July to September 2009 at Karachi, Pakistan’s
largest city both in terms of area and inhabitants.
This study was conducted at Civil Hospital Karachi,
one of the largest government tertiary care hospitals of
Karachi. The hospital has a Paediatric Emergency Unit
(PEU) specialized for the treatment of children
presenting with acute medical problems. Patients with
transfusion dependent Thalassemia (Thalassemia
major) also present to the PEU for the routine follow
up and transfusions. The fee structure of the hospital
is such that patients with lower socioeconomic strata
of the city and those referred from other centres are
Diagnosed cases of Thalassemia major that had
undergone at least ten transfusions were included after
obtaining a written consent from their care takers.
Those who did not give consent or had lesser number
of transfusions were excluded from the study.
The sampling technique was non-probability purposive
sampling. The care takers of the Thalassemia major
patients providing consent were interviewed by the
students of Dow Medical College (DMC) through a well
structured questionnaire prepared after literature search
and modified in terms of questionnaire clarity. The first
section comprised of Socio- Demographic variables.
These included age, gender, area of residency, status of
house (whether owned or at rent), monthly house-hold
income and education of the parents. The second part
was pertaining to history of vaccination for Hepatitis B
and blood group. At the completion of interview a
blood sample was obtained by venepuncture from the
patient for serological analysis of serum Ferritin levels.
The ethical approval for the study was obtained from
the Ethical Review Board (ERB) of the Dow University
of Health Sciences (DUHS).
A total of 79 patients were enrolled in the study
duration. The mean age was 10.8 ± 4.5 years. As shown in
Table 1, 46 (58.2%) were males where as the rest i.e. 33
(41.8%) were females. Half of the patients were between
ages 9 and 15 years.
Blood group “O” was found to be the predominant.
The results highlight the education status of the patients
showing that 78.8% of the care takers of the patients
had education less than the Matric (39.4% stating that
they “never went to school”, and an equal number
responding that they left the school during the primary
education). Most of the patients belonged to a poor
socio-economic background reflected from the monthly
house hold income with all the care takers having
income below 20,000 Pakistani Rupees PKR
(Approximately 245 US dollars) per month. The preponderance
(36.4%) lies between 5000-10,000 PKR (61 US
dollars122 US dollars) per month. Approximately three fourths
(75.8%) stated that they owned a house. The vaccination
history revealed that less than half (45.5%) care takers
stated that they vaccinated their children for Hepatitis B
while 12.1% not even knew whether they have carried
out the procedure or not.
The mean serum Ferritin levels were found to be
4236.5 (± 2378.3) ng/ml. The values in males were
similar (4075.2 ± 2440.7) ng/ml compared to females (4461 ±
2306.6) ng/ml. The figure was less than 1000 ng/ml in
just 2 cases, whereas the values were between two to
three thousand ng/ml in 19 cases. Figure 1 displays the
serum Ferritin ranges and the number of patients who
fall within a specified range. 11 cases had serum Ferritin
values exceeding 7000 ng/ml. The values increased
progressively with age above 9 years as suggested in Figure 2.
Desferrioxamine therapy was used by three fifth of the
patients. As expected, serum Ferritin values were much
lower (3319.6 ± 1925.8) ng/ml in the group who
received the therapy compared to those who did not use
the medication (5514.8 ± 2383.0) ng/ml. Monthly house
hold income was associated with use of Desferrioxamine
therapy, with just one third of patients below income of
3000 Rupees per month taking the medication
compared to over two thirds above that income.
Iron overload is an unavoidable complication suffered by
thalassemia major patients as a consequence of excessive
number of blood transfusions. It is so common that it
has been referred to a “second disease” during treatment
of first [
]. Serum Ferritin is an easy and in-expensive
indirect measurement of iron burden, however, a single
measure may not provide reliable indication of iron
levels. The new non-invasive methods of measuring iron
storage in the body such as MRI or SQUID have greater
sensitivity, but they have limited use in developing
countries such as Pakistan because of cost and
complexity. As excessive iron can lead to organ complications,
chelation therapy is employed to lower its levels.
Borgna-Pignatti et al reported that a lower Ferritin
concentration predicted longer survival, and reduced risk of
various complications [
]. Many studies concluded that
cirrhosis of liver is associated with increase in serum
Ferritin level [
Patients with lower socio-economic strata visit the
government tertiary care hospitals as depicted in our
results. All the patient’s care takers had a monthly
income below 20,000 rupees per month. Considering
the average 500 mg vial price of desferrioxamine to be
150-180 rupees (Approximately 5000 rupees per
month), it’s exceedingly difficult for the care takers to
cope with the therapy. These prices do not include
infusion devices, the cost of which is covered by the hospital
through governmental funding. Table 2 depicts the
effect of gender and monthly household income on the
use of Desferrioxamine therapy.
When not provided with desferrioxamine therapy the
patients suffer grave consequences of iron over load, the
spectrum of which lies from generalized weakness,
weight loss, joint pain, abdominal pain to critical illness
such as cirrhosis, hepatoma, diabetes, cardiomyopathy,
arthritis, arthropathy, hypopituitarism with
hypogonadism and death[
]. The organ most sensitive to chronic
iron overload is heart. Chronic iron over load in liver
increases chances of cirrhosis and hepatic carcinoma,
hepatoma. The death occurs mostly due to liver disease,
hepatocellular carcinoma, diabetes or cardiomyopathy
]. However, T2 weighted Magnetic Resonance
Imaging (MRI) studies show that Desferrioxamine is not as
cardio-protective as the oral chelator deferiprone as oral
deferiprone is more effective than desferrioxamine in
removal of myocardial iron [
Desferrioxamine therapy is associated with adverse effects and
demands associated with administration regimen
rendering the compliance sub-optimal. A combination regimen
of Desferrioxamine with Deferiprone is shown to be the
most rapid way of reducing iron-overload in both liver
The mean serum Ferritin level in our study was
4236.5 ng/ml, which is markedly higher when compared
to normal serum Ferritin levels in children in which the
mean serum Ferritin level is considered to be in range
of 12-122 ng/ml [
]. The values in our study are higher
compared with similar regional and international
studies. A study conducted in Islamabad, the federal capital
of our country showed the mean serum Ferritin level in
patients of beta thalassemia was 3390 ng/ml [
Cunningham et al in 2004 reported mean serum Ferritin
levels in beta thalassemia patients of North America to
be 1696 ng/ml [
]. The difference is largely attributable
to the difference in the standards of healthcare between
the 2 regions. For instance, the dosage was not adjusted
with weight in our group of patients, which could
contribute to high Ferritin levels. However, Choudhry VP et
al in India reported mean serum Ferritin levels to be
6723 ng/ml [
], even higher than in our study.
Age and chelation therapy are significantly linked with
Ferritin levels in our study. This is depicted in the graph
(Figure 2) below, which outlines that there is a directly
proportional relationship between age inyears and the
serum Ferritin levels. Approximately four-fifths of the
patients in our study had serum Ferritin values
exceeding 2000 ng/ml, which is almost ten times higher than
the upper limit of normal. As expected, serum Ferritin
values were much lower (3319.6 ± 1925.8) in the group
who received the therapy compared to those who did
not use the medication (5514.8 ± 2383.0). Monthly
house hold income was associated with use of
Desferrioxamine therapy, with just one third of patients below
income of 3000 Rupees per month taking the
medication compared to over two thirds above that income.
Interestingly, female gender was associated with
increased use of Desferrioxamine therapy.
The importance of chelation therapy can be
appreciated from the fact that levels of Ferritin are inversely
linked to the survival in Thalassemia major patients. A
study reported that the 15 year cardiac disease free
survival in patients on iron chelation therapy with Ferritin
levels below 2500 ng/ml was 91% compared to under
20% with levels in excess of this value [
The height and weight (and consequently the body mass
index) of the patients was not obtained. The dose and
frequency of Desferrioxamine infusions is not
ascertained and is also a limitation.
The problems of poverty, low education level and
inadequate provision of health care are the main stumbling
blocks in effective treatment of thalassemic patients of
iron over load, the complications of which are the main
cause of morbidity and mortality in thalassemia major.
Use of Depefirone, routine measurements of serum
Ferritin levels, adherence to guidelines, awareness amongst
the public for prevention of the disease and antenatal
diagnosis are some of the methods which can decrease
the sufferings of not only the patients, but also of their
The authors are grateful to Areeba Ejaz and Muhammad Hasan, House
Officers, Civil Hospital Karachi, Pakistan for their help in data collection.
HR and TR conceived the study. HR, MUK and TR wrote the manuscript
under supervision of SA. FU, QZ, ANK and AR contributed in the study
design and data analysis. All the authors read and approved the final
The authors declare that they have no competing interests.
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