Pustika Amalia Wahidiyat

Platelet Aggregation and Activation in Thalassemia Major Patients in Indonesia

Thromboembolic events and hypercoagulable state have been reported in patients with thalassemia. As platelets play an important role in the pathogenesis of thrombosis, the authors aimed to find the pattern of changes in platelet count, function and activation, and evidence of coagulation activation in patients with thalassemia major in Indonesia. A total of 31 patients with splenectomized and 35 patients with nonsplenectomized thalassemia major were enrolled in this study. Platelet count, platelet aggregation, β-thromboglobulin, and D-dimer levels were measured. All measured parameters were significantly higher in splenectomized than in nonsplenectomized patients. β-thromboglobulin level was increased, but D-dimer level was within normal range. The authors concluded that there was an increase in platelet activation in patients with β-thalassemia major. Platelet activation was higher in splenectomized than in nonsplenectomized patients.

Evaluation of cardiac and hepatic iron overload in thalassemia major patients with T2* magnetic resonance imaging

ABSTRACT Objectives: Recent advancements have promoted the use of T2* magnetic resonance imaging (MRI) in the non-invasive detection of iron overload in various organs for thalassemia major patients. This study aims to determine the iron load in the heart and liver of patients with thalassemia major using T2* MRI and to evaluate its correlation with serum ferritin level and iron chelation therapy. Methods: This cross-sectional study included 162 subjects diagnosed with thalassemia major, who were classified into acceptable, mild, moderate, or severe cardiac and hepatic iron overload following their T2* MRI results, respectively, and these were correlated to their serum ferritin levels and iron chelation therapy. Results: The study found that 85.2% of the subjects had normal cardiac iron stores. In contrast, 70.4% of the subjects had severe liver iron overload. A significant but weak correlation (r = −0.28) was found between cardiac T2* MRI and serum ferritin, and a slightly more significant correlation (r = 0.37) was found between liver iron concentration (LIC) and serum ferritin. Discussion: The findings of this study are consistent with several other studies, which show that patients generally manifest with liver iron overload prior to cardiac iron overload. Moreover, iron accumulation demonstrated by T2* MRI results also show a significant correlation to serum ferritin levels. Conclusion: This is the first study of its kind conducted in Indonesia, which supports the fact that T2* MRI is undoubtedly valuable in the early detection of cardiac and hepatic iron overload in thalassemia major patients.

Association of pancreatic MRI R2* with blood glucose and cardiac MRI R2* among thalassemia major patients in Indonesia

1 Pediatric Hematology-Oncology Division, Department of Child Health, Faculty of Medicine, Universitas Indonesia – Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia 2 Department of Radiology, Faculty of Medicine, Universitas Indonesia – Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia 3 Department of Child Health, Faculty of Medicine, Universitas Indonesia – Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia 4 University of Southern California, Keck School of Medicine Children’s Hospital, Los Angeles, USA

The Role of Mangiferin in the Prevention of Experimentally Induced Iron Overload in an Animal Model

BACKGROUND The leaves, fruit peels, and bark of mango trees (Mangifera indica L) contain mangiferin as an active compound with known anti-oxidative and iron chelating properties. This study aims to evaluate the benefits of mangiferin in the management of iron overload. METHODS Thirty rats were divided into five groups: normal control, rats with iron overload, and rats with iron overload treated with oral mangiferin doses of 50, 100, or 200 mg/kg BW, respectively. The iron overload in this rat model was induced by means of 15 mg intraperitoneal iron dextran, twice a week for 4 weeks. Plasma mangiferin was measured using high performance liquid chromatography, plasma ferritin by using enzyme linked immunosorbent assay, and iron contents of plasma, urine, and tissues by using atomic absorbance spectrophotometry. RESULTS Plasma mangiferin concentration at doses of 50, 100, or 200 mg/kg BW were 416.10±112.04, 310.55±134.18, and 450.11±165.99 ng/mL, respectively. At 50 mg/kg BW, mangiferin significantly decreased plasma ferritin levels (from 7051.14±1368.24 to 5543.80±1225.53 ng/mL, (p=0.037). Mangiferin also showed tendency to increase urinary iron excretion and to decrease cardiac and hepatic iron accumulation. CONCLUSION In our model, oral administration of mangiferin showed non-linear pharmacokinetics and low bioavailability. At a dose of 50 mg/kg BW, mangiferin decreased plasma ferritin levels significantly. Mangiferin did not prevent the increase of plasma iron, although it exerted tendency to increase urinary iron excretion and to decrease iron accumulation in liver and heart.

Sensitivitas dan Spesifisitas α-Globin Strip Assay dalam Mendeteksi Mutasi Thalassemia-α

Latar belakang. Thalassemia-α merupakan kelainan genetik yang dapat menyebabkan gejala klinis berat pada pasien. Deteksi mutasi thalassemia-α di Indonesia umumnya menggunakan metode PCR sebagai baku emas. Saat ini, telah dikembangkan suatu metode tes strip α-globin strip assay yang lebih mudah, cepat, dan murah pengerjaannya. Tujuan. Mengetahui sensitivitas dan spesifisitas α-globin strip assay dalam mendeteksi mutasi thalassemia-α dibandingkan dengan PCR rutin. Metode. Uji diagnostik dilakukan mulai bulan Oktober 2014 sampai Maret 2015 terhadap seluruh pasien thalassemia-α beserta keluarga intinya yang berobat di RS Cipto Mangunkusumo dan Lembaga Biomolekular Eijkman. Seluruh subyek diperiksa darah perifer lengkap, indeks eritrosit, analisis Hb, morfologi darah tepi, PCR dan α-globin strip assay. Dihitung kesesuaian, sensitivitas dan spesifisitas α-globin strip assay terhadap PCR rutin dalam mendeteksi mutasi thalassemia-α. Hasil. Didapatkan 35 subyek, 17 pasien thalassemia-α dan 18 keluarga intinya. Tujuh jenis mutasi ditemukan, mutasi Hb CS dan 3,7 kb merupakan jenis dengan jumlah terbanyak (25,7% dan 17,1%). Empat subyek yang merupakan orang tua pasien ditemukan tidak memiliki mutasi. Pemeriksaan α-globin strip assay memiliki kesesuaian penuh terhadap PCR rutin sehingga didapatkan nilai sensitivitas dan spesifisitas sebesar 100%. Kesimpulan. Metode α-globin strip assay akurat dalam mendeteksi mutasi thalassemia-α sehingga dapat menjadi alternatif yang baik terhadap PCR rutin.

Endocrinopathies in Thalassemia major patients in Thalassemia Center Jakarta, Indonesia

This was a retrospective study based on the registry database in Thalassemia Center, Jakarta. We included patients who diagnosed as thalassemia major with complete data on glucose metabolism, thyroid function, pituitary-gonadal axis, bone profile, bone age, and serum ferritin level. We analyzed the association between ferritin level, chelation therapy and type of thalassemia with endocrine profile using chi-square with the significant value of 0.05. Results Complete data on endocrine profile were found in 67 subjects (31 boys, 36 girls), 23 (34%) were diagnosed as b-thalassemia homozygote and the rest as b-thalassemia/ HbE. The mean age was 16.7±5.8 years. Most of the patients (63%) received iron chelation therapy with desferrioxamine followed by deferiprone (20%) and only two patients have not taken any iron chelation therapy yet. Short stature was found in 65% of subjects, while 20% of subjects suffered from delayed puberty, 41% had hypothyroidism, and 29% had retarded bone age. None of them was diagnosed as DM or IGT, but one diagnosed as IFG. Hypocalcemia was found in 27% subjects. Subjects with serum ferritin level ≥ 2,500 ng/mL had increased risk to develop hypothyroidism, hypocalcemia and hyperphosphatemia, even though not statistically significant (p=0.58, p=0.08, respectively). Serum ferritin level also not associated with short stature and delayed puberty. Subjects with thalassemia beta-major had increased risk to develop hypothyroidism (p=0.036), but no differences found in the prevalence of short stature, delayed puberty, hypocalcemia, and hypophosphatemia (p0.17, p=0.91, p=0.60, respectively). The frequency of transfusion per year and type of chelation therapy did not influence the endocrine profiles. Conclusions This study showed that the prevalence of short stature among thalassemia patients is higher in Thalassemia Center Jakarta, while the risk to develop impaired glucose metabolism is lower, despite of poor compliance in iron chelation therapy. The risk to develop hypothyroidism, delayed puberty, and hypoparathyroidism were comparable to other studies.