Tesis

Stres Oksidatif (Malondialdehyde) pada Penderita Dewasa dengan Thalasemia Beta Mayor dan Intermedia: Perbandingan antara Sebelum dan Setelah transfusi darah serta Hubungannya dengan Muatan Besi Berlebih = Oxidative Stress (Malondialdehyde) in Adults Beta- Thalassemia Major and Intermedia: Comparison between Before and After Blood Transfusion and Its Correlation with Iron Overload.

Latar Belakang: Muatan besi berlebih merupakan masalah utama pada pasien thalasemia beta mayor dan intermedia, baik transfusion-dependent thalassemia (TDT) maupun non-transfusion-dependent thalassemia (NTDT). Muatan besi berlebih diduga dapat menyebabkan peningkatan stres oksidatif (malondialdehyde). Transfusi darah dan kelasi besi merupakan terapi utama thalasemia khususnya pada thalasemia beta mayor/TDT. Kadar malondialdehyde (MDA) plasma belum diteliti mendalam di Indonesia, terutamapada pemberian transfusi serta korelasinya dengan muatan besi berlebih. Tujuan: Penelitian ini bertujuan mendapatkan profil kadar MDA pada pasien thalasemia dewasa; membandingkan kadarnya antara sebelum dan setelah transfusi antara pasien TDT dan NTDT serta mendapatkan korelasinya dengan feritin serum (FS) dan saturasi transferin (ST). Metode: Penelitian potong lintang serta pre dan post studypada penderita dewasa thalasemia beta mayor dan intermedia yang mendapatkan transfusi darah serta dengan/atau tanpa kelasi besi di Poliklinik Hematologi-Onkologi Medik Departemen Ilmu Penyakit Dalam dan Poliklinik Thalasemia Kiara Rumah Sakit Cipto Mangunkusumo Jakarta mulai dari bulan Agustus sampai Oktober 2016. Sampel darah diambil sesaat sebelum transfusi dan satu hari setelah transfusi. FS diperiksa dengan metode electrochemiluminescence immunoassay, sedangkan ST dihitung dari kadar besi serum dibagi total ironbinding capacity dikali 100%. Kadar MDA plasma diperiksa berdasarkan metode Wills. Analisa data menggunakan T-test/Mann Whitney dan uji korelasi Pearson dan Spearman. Hasil: Sebanyak 63 orang pasien dilibatkan dalam studi, terdiri dari 51 TDT dan 12 NTDT. Rerata usia pasien adalah 29,7 (18-67) tahun. Median kadar MDA adalah 0,49 (0,21-1,33) μmol/L. Kadar tersebut tidak berbeda bermakna antara sebelum dan setelah transfusi. Median kadar MDA juga tidak berbeda bermakna antara pasien TDT dan NTDT (0,55 vs. 0,44 μmol/L; p=0,100; uji MannWhitney). Didapatkan korelasi lemah antara FS dengankadar MDA sebelum transfusi (Spearman rho=0,250; p=0,048) sedangkan tidak ada korelasi antara FS dengan kadar MDA setelah transfusi (Spearman rho=0,052; p=0,701) dan antara ST dengan kadar MDA (Spearman rho=-0,097; p=0,473). Simpulan: Median kadar MDA plasma pada pasien dewasa dengan thalasemia beta mayor dan intermediadalam penelitian ini sebelum transfusi 0,49μmol/L.Tidak ada perbedaan bermakna antara kadar MDA sebelum dan setelah transfusi dan antara pasien TDT dan NTDT. Terdapat korelasi lemah antara FS dengan MDA sebelum transfusi dan tidak terdapat korelasi FS dengan MDA setelah transfusidan ST dengan kadar MDA.
Kata kunci: malondialdehyde, muatan besi berlebih, stres oksidatif, nontransfusion- dependent thalassemia, thalassemia intermedia, transfusion dependent thalassemia.



Background: Iron overload is a major problem in thalassemic patients, either in transfusion-dependent thalassemia (TDT) or non-transfusion-dependent thalassemia (NTDT). Iron overload may increase oxidative stress (malondialdehyde/MDA). Blood transfusion and chelating iron are the main therapy for beta-thalassemia major/TDT. However, plasma MDA levels have not been well studied in Indonesia, especially its correlation with iron overload. Objective: This study aimed to profile MDA levels in adult thalassemic patients; to compare its level between before and after transfusion and between TDT and NTDT patients; and to obtains its correlation with serum ferritin (SF) and transferrin saturation (TS). Method: A cross-sectional as well as pre and post study in adult patients with thalassemia major and intermedia who received blood transfusion with/or without chelating iron in the Hematology-Medical OncologyClinic and Kiara Thalasemia Clinic in Cipto Mangunkusumo Hospital from August to October 2016.Blood samples were withdrawn immediately before transfusion and one day after transfusion.SF was assayed using electrochemiluminescence immunoassay method, while TS was calculated from serum iron divided by total iron binding capacity and multiplied by 100%. Plasma MDA levels were assayed according to Wills method. Data analysis done using T-test/Mann Whitney and Pearson and Spearman correlation test. Results: Total of 63 patients were enrolled, consisting 51 TDT and 12 NTDT patients. Patients’ mean age was 29.7 (18-67) years. Median MDA level was 0.49 (0,21-1,33) μmol/L. The level was not significantly different between before and after transfusion. Median MDA level was not significantly different between TDT and NTDT patients (0.55 vs. 0.44μmol/L; p=0.100; MannWhitney test). Weak correlation was observed between SF and MDA levels before transfusion (Spearman’s rho=0.159; p=0.214) and there is no correlation was observed between SF and MDA levels before transfusion (Spearman’s rho=0.052; p=0.701)and also between TS and MDA levels (Spearman’s rho=0.097; p=0.473). Conclusion: Median plasma MDA levels in adult patients with beta-thalassemia major and intermedia before transfusion 0,49 μmol/L. No significant different is found between MDA before and after transfusion and between TDT and NTDT patients as well. Plasma MDA levels have weak correlation with serum feritin levels before blood transfusion and not correlated with serum ferritin levels after blood transfusion and also with transferrin saturation.
Keywords: iron overload, malondialdehyde, oxidative stress, nontransfusiondependent thalassemia, thalassemia intermedia, transfusiondependentthalassemia.