CORRELATION BETWEEN SHORT STATURE WITH SERUM FERRITIN
LEVELS IN MAJOR BETA-THALASSEMIA PATIENTS AT KEDIRI DISTRICT GENERAL HOSPITAL
Grafita Dwi Kartika Sari, Chasan Ismail
Instalasi Gawat Darurat RSUD Kabupaten Kediri, Indonesia
SMF Ilmu Kesehatan Anak RSUD Kabupaten Kediri, Indonesia
gravitadwikartika@gmail.com, drchasanismail1234@gmail.com
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KEYWORDS |
ABSTRACT |
|
beta
thalassemia, ferritin levels, short stature. |
In
thalassemia, a lifelong sequence of blood transfusions leads to iron overload
characterized by increased ferritin levels. Many factors, including iron
overload may cause growth delay. High ferritin levels are believed to lead to
short stature in children with thalassemia. This study aims to determine the
correlation between short stature and ferritin levels in children with major
beta thalassemia at Kediri District General Hospital. This research is an
observational analytic with a cross-sectional design conducted on 17 subjects
of beta thalassemia major patients at Pediatric Health Sciences (IKA) Kediri
District General Hospital who met the inclusion and exclusion criteria in
December 2022-January 2023. The measuring instrument used in this study was
anthropometric status, explained through age stature, while the ferritin
levels was obtained from the patient's medical record. Spearman's rank order
correlation test was used in the analysis. There were 17 respondents, 82,36%
children in short categories and 17,64% in normal categories. The Spearman
correlation test has the p-value = 0.000 and r = -0,736. A strong negative
correlation exists between short stature and ferritin levels in
beta-thalassemia major patients at Kediri District General Hospital that
means the higher ferritin levels, the higher incidence rate of short stature. |
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DOI: 10.58860/ijsh.v2i5.51 |
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Corresponding Author: Grafita Dwi Kartika Sari
E-mail: gravitadwikartika@gmail.com
INTRODUCTION
Thalassemia is a
blood disorder that occurs in the synthesis of hemoglobin inherited in an
autosomal recessive manner which causes red blood cells to be damaged and
brittle easily. Thalassemia is divided into α thalassemia if there is an
abnormality in the synthesis of the alpha-globin chain and thalassemia if there
is an abnormal synthesis in the beta-globin chain. Beta thalassemia inherited
from both thalassemia carrier parents and shows the most severe clinical
symptoms is called thalassemia major. Thalassemia major is a chronic disease
still a big problem because it can interfere with growth and development (Wahidiyat,
2016) (Permono
& Ugrasena, 2006).
The
prevalence of thalassemia carriers in Indonesia reaches 3-8%, which means that
3-8 out of 100 people are thalassemia carriers (Ministry of Health of the Republic of Indonesia, 2022). The number of cases of
thalassemia major in Indonesia has increased from 2012 to 2018. In 2012 there
were 4,896 cases of thalassemia, and in 2018 there were 8,761 cases (Indonesia, 2022).
β thalassemia
major require regular blood transfusions throughout their lives to maintain
hemoglobin levels above 9-10.5 g/dL to suppress ineffective erythropoiesis
activity in the bone marrow and prevent growth disorders. However, repeated
blood transfusions can result in iron overload due to the continuous
accumulation of iron. In contrast, the body's ability to excrete iron is
minimal. In addition, the iron overload experienced by beta thalassemia primary
patients is also caused by increased iron absorption in the gastrointestinal
tract due to ineffective erythropoiesis. Excess iron accumulation is toxic to
tissues and can cause heart failure, cirrhosis, growth disorders, and endocrine
disorders. (Viprakasit et al., 2014) . Problems in the endocrine
glands and anemia can interfere with children's growth, causing growth
disorders such as short stature (Mariani, 2011).
Ferritin
is the main iron storage protein (Torti & Torti, 2002). Serum ferritin examination
is one of the tests that is often performed to measure the number of iron storage
in thalassemia patients undergoing transfusion therapy. Ferritin levels in patients with
β thalassemia major receiving repeated blood transfusion therapy and iron
chelation therapy are expected to be less than 1500 ng/dl (Angulo
et al., 2008).
In
Indonesia, there have been few studies regarding the relationship between short
stature with ferritin levels in patients with thalassemia beta major. Serum
ferritin considered to be representative iron overload and hemosiderosis. Early
detection of endocrine complications that in this study is short stature needed
to improve their quality of life (Evi, 2021). In thalassemic patients a common
finding is elevated ferritin levels and some studies have shown a relationship
between survival and endocrine problems in thalassemic patients using serum
ferritin as a prognostic marker. (Adil, 2012). This study aimed to determine
the relationship between short stature with ferritin levels in patients with
thalassemia beta major at Kediri District General Hospital.
METHODS
This type of
research is observational analytic with a cross-sectional design. The research
was conducted at the SMF Pediatrics (IKA) Kediri District General Hospital in
December 2022-January 2023. 17 patients with major beta thalassemia admitted.
The sample was taken using a purposive sampling method based on inclusion
criteria, namely pediatric patients aged 1- 18 years old that diagnosed with
β-thalassemia major, had blood transfusions ≥ 10 times at SMF IKA
RSUD Kediri Regency, and their parents gave their consent to participate in the
study. The exclusion criteria were patients with fever characterized by an
increase in temperature ≥ 380 C, acute infection, inflammation chronic
disease, splenectomy, and malignancy based on medical records and physical examination.
The instrument
for collecting data in this study was measuring the height using a tape measure
and the patient's age. Meanwhile, the patient's serum ferritin level data
were taken from secondary data from medical records. Data analysis to determine
the correlation between the two variables using the Spearman correlation test
with a significance value of p <0.05. 1 The software used is the statistical processing
computer program Statistical Package for Social Science (SPSS) 26.0.
RESULTS AND DISCUSSION
There were 17
samples of beta thalassemia primary patients met the inclusion and exclusion
criteria. The general characteristics of β thalassemia significant
patients at Kediri District Hospital are shown in Table 1.
Table 1.
General Characteristics of Beta Primary
Thalassemia
Patients at Kediri District Hospital
|
Sample Characteristics |
Amount (n) |
Percentage (%) |
|
Gender |
||
|
Man |
7 |
41.18% |
|
Woman |
10 |
58.82% |
|
Age |
||
|
<5 years |
2 |
11.77% |
|
5 - <10 years |
4 |
23.54% |
|
10 - < 15 years |
3 |
17.64% |
|
15 - < 18 years |
8 |
47.05% |
|
Abdomen Examination |
||
|
Splenomegaly |
5 |
41.18% |
|
Hepatosplenomegaly |
12 |
58.82% |
|
Classification Therapy |
||
|
Deferiprone |
10 |
58.82% |
|
Deferasirox |
7 |
41.18% |
Based on the study's results measuring height for age
using the z score and serum ferritin levels as shown in Table 2. The results of
the Spearman correlation test between the level of adherence to iron chelation
treatment and ferritin levels are shown in Table 3.
Table 2. Height-for-Age Values with Ferritin Levels
|
Characteristics Sample |
Amount (n) |
Percentage (%) |
|
Stature For Age |
||
|
Normal |
3 |
17.64% |
|
Stunted |
14 |
82.36% |
|
Ferritin Levels |
||
|
<1000ng/mL |
2 |
11.76% |
|
1000-2000ng/mL |
2 |
11.76% |
|
>2000ng/mL |
13 |
76.48% |
The
relationship between short stature and serum ferritin levels has a p-value of
0.000 < α 0.05 and an r-value of -0.736, so it
can be concluded that short stature growth and serum ferritin levels have a
significant and strong correlation.
Table 3.
Spearman Correlation Test Results
Between Short
Stature and Ferritin Levels
|
Short stature |
Serum Ferritin Levels |
|
R-0.736 |
|
|
0.000 |
|
|
N 17 |
Characteristics of the sample based on the data obtained showed that the
number of female samples was more than males. Namely, ten samples (66.7%) were
female, and seven (33.3%) were male. According to Mendel's law, thalassemia is
passed from parent to child in an autosomal recessive manner. The pattern of
autosomal recessive inheritance is a horizontal line so that there are many
sufferers in one generation, but not for every generation. Patients with β thalassemia
major have a 25% chance that both parents are carriers (Hoffbrand & PAH, 2013). The characteristics of the
sample based on age obtained the highest number of samples aged 15-<18 years
with eight samples (47.05%). Patients with β thalassemia major
usually appear normal at birth; symptoms will be found in children aged 2 to 6
years (Cappellini et al., 2014).
β thalassemia significant patients with
splenomegaly without hepatomegaly in 5 samples (29.41%) and hepatosplenomegaly
in 12 samples (70.59%). Splenomegaly occurs due to extramedullary
erythropoiesis (Andriastuti et al., 2016). Severe anemia in patients
with β thalassemia major causes the kidneys to release erythropoietin, a
hormone that stimulates the bone marrow to produce more red blood cells
resulting in ineffective erythropoiesisincreased erythropoiesis results in
bone marrow hyperplasia and expansion, resulting in bone deformities.
Erythropoietin also stimulates the extramedullary hematopoiesis tissue in the
liver and spleen resulting in hepatosplenomegaly (Potts & Mandleco, 2012). Based on the data obtained,
ten samples (58.82%) received Deferiprone iron chelation therapy. And seven
samples (41.18%) received Deferasirox therapy. Deferiprone is effective in
chelating iron in the heart compared to the parenteral injection of deferoxamine
(Pepe et al., 2011). Deferasirox effectively
chelates iron in the liver compared to the parenteral use of Deferoxamine (Neufeld, 2006). Iron chelation therapy is
urgently needed in patients with β thalassemia major with
repeated blood transfusions (Permono & Ugrasena, 2006). Iron chelation should be
started when ferritin levels rise above 1000 ng/mL or the patient has received
1020 units of PRC (Pepe et al., 2011).
From
this study, the results of research subjects with stunted were 14 samples
(82.36%), and the normal height was three (17.64%). Most of the major beta
thalassemia patients in this study had short stature. This is following
research at dr. Moewardi Surakarta, out of 30 samples of thalassemia patients,
22 samples (73.33%) were stunted according to the stature for age. Eight
samples (26.67%) were normal (Alifprilia, 2018). As a result of impaired
synthesis and secretion of these hormones will cause disturbances in the growth
and metabolism of patients with β thalassemia major. The growth
of people with thalassemia will be relatively normal until 9 to 10 years. Iron
buildup can interfere with osteoid maturation and precipitate into
hydroxyapatite crystals, disrupting normal bone metabolism (Moiz et al., 2018). In addition, malnutrition in
thalassemia patients is caused by ineffective erythropoiesis; the rapid
turnover of erythrocytes also increases the need (Ayukarningsih et al., 2022). The growth of patients with major
beta-thalassemia for 4-5 years when receiving regular transfusions will
experience normal growth in both body weight and height. Growth disturbances in
patients with beta-thalassemia, prominent in children under ten, are associated
with hyperactivity of the bone marrow, a few or no transfusions, and patients
experiencing hypersplenism (Bulan, 2009).
This
study found that he lowest ferritin level was 725.2 ng/mL, and the highest was
2986.7 ng/mL. Research subjects who had ferritin levels <1000 ng/mL in 2
samples (11.76%), 1000-1000 ng/ml in 2 samples (11.76%), and > 2000 ng/mL in
13 samples (76.48%). Average ferritin values range from 20-200 ng/ml (Nuari et al., 2016). The ferritin levels of the
study subjects were far above the normal range. Iron overload occurs if the
ferritin level exceeds the average value (Organization, 2017). High levels ferritin have
been strongly correlated with growth disorders, endocrine disorders or other
complications (Monaliza, 2018). So the research subject have excess iron. Iron
overload in patients with β thalassemia major is caused
by repeated blood transfusions, ineffective erythropoiesis, and increased iron
absorption through digestion. In contrast, the body's ability to excrete iron
is minimal (Cappellini et al., 2014).
The
results of data analysis using the Spearman correlation test between short
stature and ferritin levels in patients with thalassemia beta major at Kediri
District General Hospital obtained a p-value of 0.000 and an r-value of -0.736.
This shows that there is a significant result between short stature and serum
ferritin levels in patients with major beta thalassemia and has a strong
correlation. This follows previous research, which stated a significant
correlation between ferritin levels and the incidence of short stature in India
(Rathaur et al., 2020). Other studies have also
shown similar results. Multivariate analysis to test variables showed that
serum ferritin levels affected the incidence of short stature in thalassemia
children. This study also showed that age affected the incidence of short
stature apart from ferritin levels. (Fadlyana et al., 2017). Some studies show that short
stature will occur when serum ferritin levels are > 3000 ng/L. High serum
ferritin levels will cause growth disorders (Shalitin et al., 2005). Our study found a
relationship between serum ferritin levels and the incidence of short stature
caused by excess iron in the endocrine glands, which interferes with growth
hormones. (Fadlyana et al., 2017).
CONCLUSION
Based on the
results of the research that has been done, it can be concluded that there is a
significant relationship between short stature and serum ferritin levels with a
p-value of 0.000 and a strong correlation (r=-0.736) in Major beta-thalassemia
patients at Kediri District Hospital.
REFERENCES
Alifprilia, S. W. (2018). Pengaruh Kadar Feritin Serum
Terhadap Tinggi Badan pada Anak Penderita Thalasemia Mayor Di RSUD dr. Moewardi.
Amina Adil., Zain A Sobani., Abdul Jabbar., Salman. N
Adil., Safia Awan. Endocrine Complications in patients beta thallasemia
major in a tertiar care hospital in Pakistan. J Pak Med Asssoc
Andriastuti,
M., Sari, T. T., Wahidiyat, P. A., & Putriasih, S. A. (2016). Kebutuhan transfusi darah pasca-splenektomi pada
thalassemia mayor. Sari Pediatri, 13(4), 244249.
Angulo, I. L., Covas, D. T., Carneiro, A. A., Baffa, O.,
Elias Junior, J., & Vilela, G. (2008). Determination
of iron-overload in thalassemia by hepatic MRI and ferritin. Revista Brasileira de Hematologia e Hemoterapia, 30, 449452.
Ayukarningsih, Y., Amalia, J., & Nurfarhah, G. (2022).
Thalassemia And Nutritional Status In Children. Journal of
Health and Dental Sciences, 2(1), 3952. DOI :
10.54052/jhds.v2n1.p39-52
Bulan,
S. (2009). Faktor-Faktor Yang Berhubungan Dengan Kualitas Hidup Anak
Thalassemia Beta Mayor Factors Relating To Quality Of Life Children With
Thalassemia Beta Major. Universitas Diponegoro.
Cappellini,
M.-D., Cohen, A., Porter, J., Taher, A., & Viprakasit, V. (2014). Guidelines
for the management of transfusion dependent thalassaemia (TDT).
Thalassaemia International Federation Nicosia, Cyprus.
Evi
D., Aditiawati., Sari Dian P. 2021. Serum Ferritin Levels and Endocrine
Disorders in Children with Thalassemia Major. Paediatrica Indonesiana.
Fadlyana, E., Maani, F., Elizabeth, M., & Reniarti,
L. (2017). Correlation between serum ferritin level and growth
disorders in children with thalassemia. Am J Clin Med Res, 5(3),
3135.
Hoffbrand,
A. V, & PAH, M. (2013). Kapita Selekta
Hematologi Edisi 6. Jakarta: EGC.
Indonesia, K. K. R. (2022). Tha.
Sehatnegeriku.Kemkes.Go.Id. https://sehatnegeriku.kemkes.go.id/baca/rilis-
media/20220510/5739792/talasemia-penyakit-
keturunan-hindari-dengan-deteksi-dini/
Kementerian
Kesehatan Republik Indonesia. (2022). Thalasemia Bukan Penyakin Menular.
Sehatnegeriku.Kemkes.Go.Id. https://sehatnegeriku.kemkes.go.id/baca/rilis-
media/20120602/496533/thalasemia-bukan- penyakit-menular/
Mariani,
D. (2011). Analisis faktor yang mempengaruhi kualitas hidup anak thalasemia
beta mayor di RSU Kota Tasikmalaya dan Ciamis. Depok: Fakultas Ilmu
Keperawatan Program Studi Magister Keperawatan Kekhususan Keperawatan Anak.
Moiz,
B., Habib, A., Sawani, S., Raheem, A., Hasan, B., & Gangwani, M. (2018).
Anthropometric measurements in children having transfusion-dependent beta
thalassemia. Hematology, 23(4), 248252. https://doi.org/10.1080/10245332.2017.1396044
Monaliza Elizabeth., Eddy Fadlyana., Lelani Reniarti.,
Faisal., Hadyana Sukandar., Kusnandi Rusmil. (2018).
Serum IGF-1 and Short Stature in Adolescents wit Beta Thalassemia Major.
Paediatrica Indonesiana. https://doi.org/10.14238/pi58.4.2018.151-8
Neufeld,
E. J. (2006). Oral chelators deferasirox and deferiprone for transfusional iron
overload in thalassemia major: new data, new questions. Blood, 107(9),
34363441.
Nuari,
A., Tjiptaningrum, A., Ristyaningrum, P., & Basuki, W. (2016). Hubungan
Kadar Feritin Serum dengan Aktivitas Enzim AST, ALT, dan Status Gizi pada Anak
Talasemia β Mayor. Jurnal Agromedicine, 3(1), 2629.
Organization,
W. H. (2017). Indicators Serum Ferritin.
http://www.who.int/vmnis/indicators/serum_ferriti n.pdf
Pepe, A., Meloni, A., Capra, M., Cianciulli, P.,
Prossomariti, L., Malaventura, C., Putti, M. C., Lippi, A., Romeo, M. A., &
Bisconte, M. G. (2011). Deferasirox, deferiprone and
desferrioxamine treatment in thalassemia major patients: cardiac iron and
function comparison determined by quantitative magnetic resonance imaging. Haematologica, 96(1),
4147.
Permono, B., & Ugrasena, I. D. G. (2006). Hemoglobin
abnormal: talasemia. Dalam: Permono B, Sutaryo, Ugrasena IDG, Windiastuti E,
Abdulsalam M, Editor. Buku Ajar Hematologi-Onkologi Anak. Edisi, 3,
6484.
Potts, N. L., & Mandleco, B. L. (2012). Pediatric
nursing: Caring for children and their families. Cengage
Learning.
Rathaur,
V. K., Imran, A., & Pathania, M. (2020). Growth pattern in thalassemic
children and their correlation with serum ferritin. Journal of Family
Medicine and Primary Care, 9(2), 1166. doi:
10.4103/jfmpc.jfmpc_951_19
Shalitin,
S., Carmi, D., Weintrob, N., Phillip, M., Miskin, H., Kornreich, L., Zilber,
R., Yaniv, I., & Tamary, H. (2005). Serum ferritin level as a predictor of
impaired growth and puberty in thalassemia major patients. European Journal
of Haematology, 74(2), 93100. https://doi.org/10.1111/j.1600-0609.2004.00371.x
Torti,
F. M., & Torti, S. V. (2002). Regulation of ferritin genes and protein. Blood,
99(10), 35053516.
Viprakasit,
V., Origa, R., & Fucharoen, S. (2014). Genetic basis, pathophysiology and
diagnosis. In Guidelines for the Management of Transfusion Dependent
Thalassaemia (TDT)[Internet]. 3rd edition. Thalassaemia International
Federation.
Wahidiyat,
I. (2016). Thalassemia dan permasalahannya di Indonesia. Sari Pediatri, 5(1),
23.
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