LIMITATION ON SUPPORTING EXAMINATION FACILITIES FOR THALASSEMIA B MAJOR

PATIENT MANAGEMENT ON ABDUL MANAF HOSPITAL

Nindya Aryanty1), Mustarim2), dan Huntari Harahap3)

1)
Universitas Jambi
nindyaaryanty@unja.ac.id
2)
Raden Mattaher Hospital
mustarim12@yahoo.com
3)
Universitas Jambi
huntariharahap@gmail.com

ABSTRACT

Thalassemia B Major is a genetic illness characterized by anemia from an early age resulting in a lifelong
dependency on routine blood transfusions that increase the risk of multi-organ dysfunction due to iron
overload. To standardize the management of thalassemia, the Ministry of Health, in 2018, published the
National Guidelines for Thalassemia Medical Service Management. Until now, research evaluating the
implementation of these guidelines in Indonesia has not been recorded. This research qualitatively
evaluates the management of children with Thalassemia in Abdul Manaf Hospital in Jambi. The study
was conducted through an in-depth-interview with 13 children with Thalassemia who were treated at
Abdul Manaf Hospital and their caregivers. The data triangulation was carried out through interviews
with the pediatricians and paramedics involved in the thalassemia services and by using field notes. This
research found the limitations on the supporting examination facilities in the Thalassemia services at
Abdul Manaf Hospital as a center for thalassemia management in Jambi province. Unavailability in
examining hemoglobin electrophoresis and DNA analysis hinder diagnostic conclusion. Evaluation of
iron overload through ferritin measurement also not available. Considering an expensive cost for ferritin
examinations in a private laboratory, Ferritin measurement is only recommended once a year and
encouraged through facilitated cost-sharing by other parties. Evaluation of the side effect of iron chelation
drugs on liver and kidney function is conducted once a year instead of every three months. MRI T2* to
examine heart complications due to iron overload also not available at the hospital hence
echocardiography examination is conducted to substitute the evaluation of heart function. Another
problem arose since the Social Security Administrator for Health declare a policy to limit the payment of
echocardiography examination only for those with the abnormal result so then echocardiography is no
longer used for heart complication screening for thalassemia patient. Limitations on the supporting
examination facilities in the Thalassemia services at Abdul Manaf Hospital affect the quality of the
thalassemia management hence negatively influence the children's health. Hospital directors need to
urgently discuss with Jambi province government to fulfill all the equipment needed to be able to deliver
high-quality thalassemia management for the patient.

Key word: limitation, supporting examination, health influence

 Thalassemia is an inherited hemoglobin disorder that has already become a pervasive
disease worldwide. It is highly prevalent in sub-Saharan Africa, the Mediterranean region and
the Middle East, the Indian subcontinent, east and southeast Asia, called the Thalassaemia belt,
so that over 90% of patients were coming from low-income and middle-income countries. 1,2
Indonesia, located along the belt, bear the burden of enormous thalassemia cases. It is estimated
that 5% of its 260 million population carrying these thalassemia genes. With a birth rate of
around 20% annually, there will be approximately 2500 new thalassemia major cases per year, 2
contribute to increasing economic burden for the country due to its lifelong management with
blood transfusions and iron chelation therapy.3

World Bank Data considers Indonesia as an emerging middle-income country.

Thalassaemia medical costs to health services which are ranged from $US 873 to almost $40,000
per patient year4 surely become a huge burden for the country. To standardize the management
of thalassemia in Indonesia, the Ministry of Health, in 2018, published the National Guidelines
for Thalassemia Medical Service Management.5 An article that discussed thalassemia care in
Cipto Mangunkusumo Hospital which is located in the nation's capital still found many
limitations on thalassemia patient management. It is presumed that many rural areas in Indonesia
might suffer from substandard health facilities hence affecting healthcare quality. This article
reviews the limitation on supporting examination facilities for thalassemia B major patient
management on Abdul Manaf hospital which is located in the capital city of Jambi Province.

The study was conducted qualitatively through an in-depth interview with 13 children
with Thalassemia who were treated at Abdul Manaf Hospital and their caregivers. The data
triangulation was carried out through interviews with the pediatricians and paramedics involved
in the thalassemia services and by using field notes. A purposeful sampling method was used
until data saturation was achieved. The interview was recorded and then transcripted. Data
analysis was performed with a qualitative analysis method using content analysis. Interview
transcripts were reviewed several times, and then, data were extracted into open coding which
was then categorized into related theoretical code. Data were then summarized into several main
categories.

Results
 This study was conducted through interviews with 13 children with Thalassemia and
their caregivers who were present at the time of data collection while undergoing treatment at the
Children's Clinic and/ or the transfusion room at Abdul Manaf Hospital. Data were collected
through interviews with two Pediatricians, a pediatrician nurse, four nurses in the transfusion
room, and a pharmacist at Abdul Manaf Hospital.
RSUD Abdul Manaf was designated as a Thalassemia service center in 2013 in Jambi
Province. Outpatients data show an increase in the number of pediatric thalassemia patients at
Abdul Manaf Regional Hospital, from 2011 until 2012 as many as 16 people and increased in
2013 by about 252 people. RSUD Abdul Manap has become a referral center for Thalassemia
patients from almost every district in Jambi City since 2013, Restriction policy regarding
medical services by the Healthcare and Social Security Agency (BPJS) was implemented in 2019
so it's returning thalassemia patients from the regions to the respective district hospitals.
Currently, the majority of pediatric thalassemia patients who seek treatment at Abdul Manaf
Hospital are mostly from Jambi City, only a small number of patients from other districts came
for treatment due to limited blood transfusion facilities in their home districts. Pediatric
Thalassemia patients respondents in this study from districts outside Jambi City including from
Tanjung Jabung Timur and Merangin, which are respectively 3 hours and 8 hours drive to Abdul
Manaf Regional Hospital.

As a management center for Thalassemia, RSUD Manaf is certainly expected to provide

Thalassemia medical services according to predetermined standards. However, this study found
several conditions that contributed to inadequate management, including the limitations of
supporting facilities.

The unavailability of hemoglobin electrophoresis and DNA analysis in laboratory

services causes obstacles in the diagnosis of Thalassemia. The Abdul Manaf Hospital laboratory
can only perform routine blood tests with peripheral blood smears to support the diagnosis.
Generally, parents of patients with suspected thalassemia are motivated to be willing to pay
independently for the cost of Hb electrophoresis examination in a private laboratory. However,
several patients who could not afford the examination fees were forced to postpone the
examination or even not undergo the examination.

Most of them do their best so at least we can carry the peripheral blood when advice from
the clinical pathologist has done, and the clinical sign is pointing towards hemolytic,
usually, the pathologist writes down Hb electrophoresis advice, so we will ask the family
for the agreement ...

With a few notes that Hb electrophoresis at least possible for 3 months later after the first
admission, parents must effort so that Hb doesn't get lower anymore. Usually, the new
patient came with a moderate Hb level, so they can wait for their turn, so once the blood
test result comes out, we can do Hb electrophoresis and we just need to call the lab and
asked for the cost. After the parents give their agreement, the laboratory staff will check
them. Sometimes we can get discount vouchers right by coincidence, for example, the lab's
birthday, at that time I had been coming at Prodia's birthday and received a discount.
Fortunately, (Doctor 2) If it's an emergency, we are supposed to do a transfusion later..

Another diagnostic examination using DNA analysis which also cannot be done in hospital
laboratories causes only some children from families who are affordable to undergo the
examination. "... In one or two cases they went alone to Jakarta because they were capable
of financial" (Doctor 1)

One of the parents of a Thalassemia patient who was clinically diagnosed with
Thalassemia at the age of 1.5 years, and now their child is 4 years old, admitted that he
still had not brought the child to undergo a diagnostic Hb electrophoresis examination due
to cost constraints. "I have no funds temporarily. I must have Rp 700.000 for each check…
"(M's parent). The patient comes from Tanjung Jabung Timur Regency who must head
overland about 3 hours to arrive at Abdul Manaf Hospital with the cost of public
transportation around Rp 700,000. The patient's parents work as casual daily laborers
with an average income of Rp. 50,000 per day.

Temporarily, I didn't have enough cost. For every check(Hb Electroforesist) I need at least
Rp 700.000. It's the fact that a day I must prepare Rp 1.000.000 for my round-trip ticket of
the transportation. (Respondent 01)
Patients who required a blood transfusion at least once a month were only able to be admitted to
the hospital once every three months with an average pre-transfusion Hb level of 4 g / dl per
arrival. Three months before the interview, the patient received a blood transfusion at RSUD X
which is the provincial referral hospital. Because the patient had not done a diagnostic
examination of Hb electrophoresis, the patient could not get iron-chelating drugs. Currently, in
treatment at Abdul Manaf Hospital, patients can still get iron chelation drugs but the drugs given
are not enough for 3 months of use because for one time taking deferiprone is only limited for a
month's needs. Unlike the case with deferasirox prescription, which can only be prescribed for
15 days of use.

... once taking the drug [deferiprone] per month, ration for one month ...

… Exjade [deferasirox] is more expensive, even though they drink it once a day they only g
et 15 days (Doctor 2)

Apart from the limitations of diagnostic tests, there is also difficulty in evaluating iron
deposits because Ferritin testing is also not available in hospital laboratory services. Abdul
Manaf Hospital's Thalassemia patients are motivated to pay independently to undergo Ferritin
examination in a private laboratory. The high cost of examinations in private laboratories means
that Ferritin examinations are only recommended once a year which is sought by receiving fee
relief assistance..

"Nothing, serum ferritin isn't there. I usually got from the laboratory. I strive to get it from
the pharmacy so that they can help support the serum ferritin check by giving a voucher
once a year, but now they couldn't do it (Doctor 1)

Checking ferritin once a year is a guideline in choosing iron chelation treatment. Patients with
high ferritin levels, for example,> 2000 ng/ ml, will receive a combination of oral drugs with
deferoxamine. Some patients were informed that they were not taking adequate oral iron
chelation drugs due to the constraints that the distance from the house to the hospital was too far
so that the parents had difficulty bringing the control patient to seek treatment for iron chelation.
The administration of intravenous deferoxamine administration is also hampered by a single
syringe pump, which is a grant from the Indonesian Thalassemia Foundation. So that each
patient with a high Ferritin value only gets one administration of deferoxamine from ideally five
times a week..

Regarding the need to evaluate the side effects of iron chelation drugs through laboratory tests of
liver and kidney function, Thalassemia patients at Abdul Manaf Hospital receive a one-year
check-up schedule. Periodic checks to rule out transfusion-borne diseases are only performed for
HBsAg once a year. Anti-HCV was not tested because reagents were not available in the
laboratory.

[examination of liver function, kidney function] Once a year for all patients. Actually,
there is a timeline, from the management of thalassemia, there are those who are checked
twice, there are 3 times 2 times even 1 time, but we are usually a bit minimalist. We choose
2 times only per year (Doctor 1)

… We only checked HBsAg, we actually should have C [anti-HCV] at most, actually Hep
C [Hepatitis C] but we just take HBsAg because that's the reagent we have (Doctor 1)

Examination of cardiac complications due to iron deposits, ideally using T2* MRI but,
cannot be done because the tools are not available. Evaluation of heart function is replaced by
echocardiography examinations which are only scheduled once a year. Currently, there are still
problems due to the policy of the BPJS, which does not cover the cost of examinations if normal
results are obtained. So that currently echocardiography is no longer used to screen for cardiac
complications in Thalassemia patients..

… One of the obstacles is that our echo is giving once a year only, but the problem is that BPJS
doesn't even pay for normal echo, so we get dizzy. What we aim for this exam, we can examine
the patient first and we can know the abnormality earlier, but the doctor couldn't get paid if the
ECHO examination is normal instead. The cardiologist gave up, no need to [check echo] here
[RSUD Abdul Manaf], just outside [Hospital]. How patients with BPJS insurance couldn't
[refer] outside to get echo ... we don't have cardiologist here.. echo this year is stuck (Doctor 2)

Discussions
 Allen, et al. Have expressed concern about the unavailability of basic health services
needed in the management of thalassemia. 7 Thalassemia is thought of as a disease that has no
hope of cure so that investment in medical equipment is considered a waste. Allen, et al. Stated
that the difficulty in providing laboratory services for diagnostic clinics due to limited resources
also occurs in various hospitals and referral laboratories in big cities in Sri Lanka, especially the
limitations experienced in hospitals and health centers in rural areas. Limited equipment,
disposable materials, reagents, and limited supply of water and electricity are the challenge to be
able to provide great quality services..

This study found that RSUD Abdul Manaf has not conducted a Hb electrophoresis
examination or DNA analysis to diagnose Thalassemia. Wahidiyat, et al 2 presented a description
of the management of Thalassemia medical services in Indonesia, especially at Cipto
Mangunkusumo Hospital, Jakarta. Thalassemia patients who are referred for specialized medical
services will generally receive conventional hemoglobin analysis using electrophoresis or the
HPLC method. Meanwhile, DNA analysis which is not covered by national health insurance can
only be done by a small group of patients because of the very high cost. Wahidiyat, et al also
explained that the hemoglobin analysis examination is currently owned by most regional
hospitals while DNA analysis is only available in a few big cities in Indonesia. This study found
that both the provincial referral hospital and Abdul Manaf Hospital as the Jambi city reference
hospital which is located in the center of the capital city, have not been able to provide
hemoglobin analysis examination services while DNA analysis-only. Hemoglobin analysis
checks should be covered by the BPJS because it can only be obtained from laboratory services
which are not affordable. It resulted in Thalassemia patients who come from poverty families
unable to perform this diagnostic test. It certainly will affect the accuracy of the management
diagnosis and prognosis of the patient. This condition is inversely proportional to efforts to
control the incidence of thalassemia through genetic screening and counseling programs.

This study found that ferritin testing was not yet available in the laboratory services of
Abdul Manaf Hospital. The same condition was also found in the study of Allen, et al 7 in Sri
Lanka. The limitation of serum ferritin in measuring the complications of iron deposits in
patients with thalassemia precludes a reliable determination of the patient's clinical status. This
further affects the quality of medical treatment given to patients because it is not based on
evidence regarding the patient's actual medical condition. Furthermore, Allen, et al. Formulated
the necessary remedial solutions due to the limitations of this supporting examination that apart
from completing the equipment, training for laboratory staff to be able to operate the equipment
properly is also necessary.

The use of iron chelation therapy is needed to minimize iron buildup due to repeated
blood transfusions in Thalassemia patients. However, the iron chelation drug used also has side
effects that need to be evaluated periodically so that the side effects that occur can be managed
adequately as early as possible. Monitoring renal function, a liver function that is currently being
administered once a year needs to be supplemented with various other side effect examinations
according to the type of iron-chelating drug obtained by the patient, according to the examination
schedule (table 1).

Table 1. Iron chelation side effects and warnings 6

 The need for repeated blood transfusions increases the risk of becoming infected with
transfusion-borne diseases such as Hepatitis B, Hepatitis C, and HIV. Currently, Thalassemia
patients at Abdul Manaf Hospital only undergo an evaluation for Hepatitis B surface antigen
(HBsAg) once a year to evaluate the risk of Hepatitis B infection. Medical services need to be
improved to also accommodate the need for periodic evaluation of Hepatitis C antibody (anti-
HCV) and HIV antibody (anti-HIV filter). 6

Thalassemia β major patients who require routine blood transfusions throughout their life are at
risk for developing iron deposits, especially in the heart organ. Therefore, periodic evaluation to
identify complications in the heart organ is very important to do. Examinations to help detect
complications in the heart include the examination of the iron profile, ECG, echocardiography,
and MRI T2 *.6 This study found limitations in the examination of the iron profile by measuring
ferritin levels. Abdul Manaf Regional Hospital also does not have radiological equipment for T2
* MRI examinations. Currently in Indonesia, only two T2 MRI devices are available, in Aceh
and at Cipto Mangunkusumo Hospital-Jakarta.2 Therefore, evaluation of cardiac complications
can be pursued through electrocardiography and echocardiography examinations.
Electrocardiography can detect arrhythmias. Meanwhile, echocardiography can be done to
monitor heart function regularly. Echocardiography can be used to assess the systolic function of
the heart by measuring the ejection fraction and ventricular volume. However, although RSUD
Abdul Manaf has echocardiography equipment and cardiac specialist staff, echocardiography
examinations at this time also cannot be used for periodic evaluation of heart function because
the new BPJS policy will approve examination claims if abnormal echocardiography results are
obtained. This is certainly not in line with the monitoring of heart function which aims to
evaluate and identify early impaired heart function in Thalassemia patients so that it can be
managed immediately adequately. Cardiac complications that occur are still reversible with
intensive iron chelation administration, especially using deferoxamine. However, the
administration of deferoxamine at Abdul Manaf Hospital is currently also constrained by the
syringe pump, which is only available in one unit and is used alternately for several patients.

Conclusions

Limited facilities and policy constraints in health services contribute to the inadequate
management of thalassemia at Abdul Manaf Hospital, Jambi. Pediatricians who are in charge of
Thalassemia services need to communicate the various obstacles faced by the Hospital Directors
and related stakeholders such as BPJS and the Jambi City government so that together they can
solve the problems due to limitations of supporting examination facilities in the management of
Thalassemia β major at Abdul Manaf Hospital.
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Blood Transfusion, ISBT Science Series.2020:0;1–8
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Indonesia: Screening Program, Diagnosis and Research. HEMOGLOBIN. 2019:
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