Iron-Chelating Therapy for Transfusion-Dependent Thalassemia Patients with Renal Failure :

an Evidence Based Case Report

Bonita Effendi1, Aditia Reza1 , Nadia Ayu Mulansari2
1
Department of internal Medicine, Medical Faculty University of Indonesia/Cipto Mangunkusumo
Hospital.
2
Division of Hematology and Oncology ,Department of Internal Medicine, Department of Internal
Medicine, Medical Faculty University of Indonesia/ Cipto Mangunkusumo HIspotal.

Abstract

Background : Limited studies investigate renal involvement in beta-thalassemia. Retention of excess iron
from blood transfusion in organs in thalassemia patients may cause several systemic complications. Iron
chelating agents play role in reducing such iron overload. It is essential to understand the impact of renal
impairment on iron chelators. The aim of this study is to determine efficacy and safety of iron-chelating
in Thalassemia patients with renal failure.

Methods : A search was conducted on Pubmed, Science Direct, and EBSCOhost. The selection of title and
abstract was conducted using inclusion and exclusion criteria, which resulted to three relevant articles.
The selected studies were critically appraised for its validity, importance, and applicability. Inclusion
criteria, exclusion criteria.

Results : Three relevant articles were found, renal injury is multifactorial and progressive in thalassemia
patients. Previous study compared deferasirox and deferoxamine with deferiprone combination therapy
in patients with renal dysfunction. Both showed glomerular dysfunction with proteinuria and tubulopathy.
Yet in other study showed Deferasirox may improve iron metabolism in patients with hemodialysis with
iron overload, and shows tolerable response to be used in renal failure patients. Another study also
reported there is no adjustment of dosage needed for Deferiprone in patients with renal impairment.

Conclusion : Choice of chelating therapy should be individualized based on drugs availability, drugs
tolerability, and trends on organ-specific iron loading.

Total word count : 221

References:

1. Economou M, Printza N, Teli A, Tzimouli V, Tsatra I, et al. Renal dysfunction in patients with beta-
thalassemia major receiving iron chelation therapy either with deferoxamine and deferiprone or
with deferasiroz. Acta Haematol. 2010; 123(3):148-52.
2. Chen CH, Shu KH, Yang Y. Long-term effects of an oral iron chelator, deferasirox, in hemodialysis
patients with iron overload. Hematology. 2015 Jun; 20(5):304-10.
3. Fradette C, Pichette V, Sicard E, Stilman A, Jayashankar S, et al. Effects of renal impairment on the
pharmacokinetics of orally administered deferiprone. Br J Clin Pharmacol. 2016; 82: 994-1001.
DEN 3,2,1,4 (Indonesia)

Berikatan dengan virus—opsonisasi

Membungkus virus dengue sehingga lebih mudah dikenali

Sehingga mudah masuk intrasel, mudah interaksi di intrasel – secreted pathway

Limfosit monosit hepatosit dan dendritic sel

Infeksi yang kedua kali dengan serotipe yang berbeda, karna serotipe yang berbeda, akan membungkus
serotipe yang dikenali oleh sel manusia sehingga viral load nya meningkat

Tetravalent immunization

Orang gemuk lebih sulit: infeksi , kemamouan tubuh utk mengeliminasi virus lebih sulit

Di permukaan sel endotel, glycoprotein cell rceptopr, akan ditutupi glucocalyx, di dalam glycocalyx ada
reseptor2, jika terkikis maka GPCR akan terpantau

Occluding DHF > DF lebih banyak ditemukan dalam darah

Menunjukkan tight junction terganggu.

3 sistem (vaskuler endotelial)

Sel hati – peningkatan SGOT dan SGPT

Sel imun target

Kapiler endotel

Cytokine tsunami

Selapis endotel

Pertahanan awal : tight junction, adherence junction (hanya bisa dilalui di <3 nanometer)urea glucose ions
– paracellular pathway / intracellular junction

Case Ilustration
A 47-year-old female suffered dyspnea since 2 weeks before hospital admission. She has been diagnosed
with Thalassemia since 2 years ago and has received routine transfusion. From physical examination there
was tachypnea, anemic sclera, and hepatosplenomegaly. Her Hb analysis showed HbA 92.1% (low), HbA2
5.9% (high), HbF 2.00% (high). Other supporting examination showed MRI T2* heart 30.01 ms, MRI T2*
liver 1.16 ms, and MRI T2* pancreas 17.96 ms, increased Fe 191, increased TIBC 180, increased Transferin
saturation 106%, and increased Ferritin 30574. During hospital admission, she was at anemia gravis
condition, her hemoglobin level was 4.03 g/dL; thrombocytopenia (84000/uL). Then, her creatinine level
has increased, 4.46 mg/dL (eGFR 12.4 mL/min/1.73 m2) with increased total bilirubin 1.10 mg/dL.
deferiprone, fever always occurs. Her renal impairment becomes an issue in choosing iron-chelating
agents. During hospitalization, fever and dyspnea occurred when admission of Deferiprone. While,
Deferasirox might be difficult to be admitted since her renal impairment. In this review, we will discuss
the issue of choosing iron-chelating agent e in thalassemia patient with renal impairment.