Pustika Amalia Wahidiyat
Departemen Ilmu Kesehatan Anak Fakultas Kedokteran Universitas Indonesia/RS. Dr. Cipto Mangunkusumo, Jakarta

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Prevalence of hepatitis and its correlation with serum ferritin and aminotransferase levels among thalassemia major patients in Indonesia Pustika Amalia Wahidiyat; Felix Liauw; Nitish Basant Adnani; Siti Ayu Putriasih
Paediatrica Indonesiana Vol 57 No 4 (2017): July 2017
Publisher : Indonesian Pediatric Society

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (344.183 KB) | DOI: 10.14238/pi57.4.2017.176-80

Abstract

Background Thalassemia major patients who undergo routine transfusion have an increased risk of acquiring transfusion-transmitted infections (TTI), including hepatitis B and C. These diseases have serious implications and may affect the serum ferritin and aminotransferase levels of thalassemia major patients.Objectives To identify the prevalence of hepatitis B and/or C infections among thalassemia major patients and to evaluate its correlation with serum ferritin and aminotransferase levels.Methods This was across-sectional study conducted at the Thalassemia Center of Dr. Cipto Mangunkusumo Hospital in Jakarta, Indonesia. The subjects were screened for hepatitis B and C infections, and their serum ferritin and aminotransferase levels were also measured.Results In total, 621 subjects were included in the study, among which 5 subjects tested positive for hepatitis B surface antigen (HBsAg) (0.8%), 111 subjects tested positive for anti-HCV (17.8%), and 5 subjects tested positive for both HBsAg and anti-HCV (0.8%). The subjects who tested positive for hepatitis B, hepatitis C, or both showed significantly higher values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum ferritin compared to their negative counterparts. Moreover, serum ferritin showed a positive, moderate correlation with both AST and ALT.Conclusion This study shows a significant association between hepatitis and serum ferritin as well as aminotransferase levels. Early detection and early management of hepatitis B and C infections is warranted to minimize the occurrence of liver damage in thalassemia major patients. 
Side effect of deferiprone as iron chelator in patient with thalassemia Mikhael Yosia; Pustika Amalia Wahidiyat
Paediatrica Indonesiana Vol 57 No 6 (2017): November 2017
Publisher : Indonesian Pediatric Society

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (141.717 KB) | DOI: 10.14238/pi57.6.2017.329-36

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Background There are currently three available iron chelators: deferoxamine (DFO), deferasirox (DFX) and deferiprone (DFP). In Dr. Cipto Mangunkusumo Hospital and Indonesia, in general, the accessibility of DFP for thalassemia patients has been adequate. Even though its efficacy in removing iron has been proven by countless studies, questions relating to its safety and possible side effects continue to be raised. Objective To assess common side effects of DFP usage by an intensive literature search and compare them to that in a pediatric thalassemia patient, in order to determine if the child's symptoms in the were potentially caused by DFP. Methods A literature search using MeSH terms was done in PubMed. Full copies of articles that fulfil the inclusion criteria, based on their title, abstract, and subject descriptors, were critically appraised using The Joanna Brigs Institute (JBI) critical appraisal tools. Results A total of 10 research articles from 1998-2013 were deemed applicable to this study including: 2 case reports, 5 prospective cohort studies, 2 retrospective cohort studies, and 1 randomized control trial with a grand total of 1,026 samples. Conclusion Side effects of DFP include: neutropenia, agranulocytosis, increased ALT, gastrointestinal problems, arthralgia or arthropathy, increased appetite or weight, thrombocytopenia, urine discoloration, as well as auditory and visual disturbances. Our case report patient's symptoms of gum bleeding and haemorrhagic mass are not related to her DFP consumption.
Oxidative stress in neonates with hyperbilirubinemia before and after phototherapy: malondialdehyde and catalase activity Putu Junara Putra; Rinawati Rohsiswatmo; Pustika Amalia Wahidiyat
Paediatrica Indonesiana Vol 58 No 6 (2018): November 2018
Publisher : Indonesian Pediatric Society

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (214.323 KB) | DOI: 10.14238/pi58.6.2018.269-73

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Background Phototherapy is used to treat neonatal hyperbilirubinemia, but is currently thought to cause photodynamic stress and can induce lipid peroxidation. There is increasing evidence that many severe diseases of the neonates are caused by oxidative injury and lipid peroxidation. In the present communique, we review the oxidative succeptibility of the neonate and the evidence now available that phototherapy induces oxidative stress. Malondialdehyde (MDA) is a metabolic product of free radicals. Catalase is a antioxidant that binds free radicals. Objective To compare the levels of oxidants and antioxidants before and after phototherapy in neonates with hyperbilirubinemia. Methods This pretest-posttest control group study was conducted in Sanglah Hospital, Bali from November 2016 to April 2017. Thirty babies with gestational age ≥35 weeks and hyperbilirubinemia with total bilirubin levels requiring phototherapy were included in this study. The MDA levels and catalase activity were measured before and after 24 hours of phototherapy. Results Comparative analysis using paired T-test showed a significant increase of malondialdehyde level, with mean MDA 23.73 (SD 8.20) nmol/mL before and 53.05 (SD 10.18) nmol/mL after phototherapy (P<0.001). However, catalase activity significantly decreased from of 72.33 (SD 10.63) kU/L before phototherapy to 44.85 (SD 14.79) kU/L after phototherapy (P<0.001). The MDA level had a significant, negative association with catalase activity after phototherapy (r =-0.4; P=0.028). Conclusion Neonates with hyperbilirubinemia are found to have increased oxidative stress after phototherapy, as indicated by increased MDA levels and decreased CAT activity after 24 hours of phototherapy.
Hemostatic abnormalities in children with thalassemia major and liver iron overload Pustika Amalia Wahidiyat; Stephen Diah Iskandar; Novie Amelia Chozie; Damayanti Sekarsari
Paediatrica Indonesiana Vol 58 No 4 (2018): July 2018
Publisher : Indonesian Pediatric Society

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (217.634 KB) | DOI: 10.14238/pi58.4.2018.175-9

Abstract

Background Thalassemia major (TM) patients are susceptible to liver dysfunction due to iron deposition. Pediatric TM patients often present with bleeding. Blood loss necessitates transfusions, leading to increased iron absorption from the gut. Objective To study hemostatic abnormalities in children with TM and iron deposition in the liver. Methods This cross-sectional study involved 190 non-splenectomized children with TM. Liver iron deposition was evaluated using T2* MRI. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet counts were assessed from blood specimens. Results Most subjects were diagnosed with β-thalassemia and β-thalassemia/HbE. The majority of subjects were on deferiprone (DFP) treatment. Approximately 89.5% of subjects had liver iron overload. Prolongation of PT and aPTT, as well as thrombocytopenia were observed in 60%, 27.9%, and 19.5% of subjects, respectively. Prolonged aPTT and thrombocytopenia were observed three times more frequently in subjects with moderate - severe liver iron overload than in subjects with normal - mild liver iron overload (P=0.04 and 0.001, respectively). Conclusion Most TM subjects have liver iron overload ranging from mild to severe. Prothrombin time and prolongation, as well as aPTT prolongation, and thrombocytopenia are easily found in TM children. There were significantly more moderate - severe liver iron deposition patients with aPTT prolongation and thrombocytopenia than normal – mild patients with these conditions. Hence, we suggest that pediatric TM patients undergo liver iron deposition evaluations and use iron chelators in an optimal manner, in order to limit the risk of bleeding.
Liver iron overload and hepatic function in children with thalassemia major Pustika Amalia Wahidiyat; Stephen Diah Iskandar; Ludi Dhyani Rahmartani; Damayanti Sekarsari
Paediatrica Indonesiana Vol 58 No 5 (2018): September 2018
Publisher : Indonesian Pediatric Society

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (273.956 KB) | DOI: 10.14238/pi58.5.2018.233-7

Abstract

Background Routine blood transfusions and increased intestinal iron absorption lead to iron accumulation in various organs, especially the liver. To date, T2-star magnetic resonance imaging (T2*MRI) is a valuable tool to evaluate iron level in organs. Objective To assess the degree of liver iron overload among children with thalassemia major (TM) and its possible correlations with hepatic function laboratory values. Methods This cross-sectional study was conducted in Cipto Mangunkusumo Hospital. The degree of liver iron overload was evaluated by T2*MRI. Assessments of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and bilirubin levels were done to evaluate liver function. Results A total of 291 TM children were included in this study. The mean age of subjects was 12 years. Most of the subjects were diagnosed as β-thalassemia homozygote (54.6%) and β-thalassemia/HbE (41.2%). Deferiprone (DFP) was the most commonly used iron chelator. Less than 10% of the subjects had normal liver iron deposition. The AST and ALT values increased proportionally with the severity of liver iron overload, with significant, moderately negative correlation coefficients (r=-0.388 and -0.434, respectively). However, albumin level decreased proportionally with the severity of liver iron overload, with a significant, moderately positive correlation coefficient (r=0.323). Liver T2* MRI had no significant correlations with direct, indirect, and ratio of direct/total bilirubin levels. Conclusion Most of the children with TM have mild to severe liver iron overload. Liver T2* MRI had significant, moderate correlations with AST, ALT, and albumin values. Bilirubin level has no correlation with T2* MRI. Our findings suggest that monitoring of AST, ALT, and albumin levels is important because they may reflect the severity of liver iron overload. However, they should not be used as the only predictors of iron overload.
Comparative efficacy, safety, and cost of iron chelation monotherapy vs. combination therapy in pediatric beta-thalassemia major: a single-center retrospective study Dewi Sharon Simorangkir; Nafrialdi Nafrialdi; Pustika Amalia Wahidiyat; Vivian Soetikno
Paediatrica Indonesiana Vol 62 No 2 (2022): March 2022
Publisher : Indonesian Pediatric Society

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14238/pi62.2.2022.91-7

Abstract

Background Iron chelation therapy is used to maintain iron balance in β-thalassemia major patients who undergo repeated blood transfusions. Objective To compare the efficacy, safety, and cost of iron chelation combination regimens [deferiprone (DFP) + deferoxamine (DFO) or DFP + deferasirox (DFX])] vs. high-dose DFP monotherapy (≥ 90 mg/kg/day) in pediatric β-thalassemia major patients. Methods This cross-sectional, retrospective study was done at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Retrospective data was obtained from electronic medical records of pediatric b-thalassemia major patients with serum ferritin of ≥ 2,500 ng/mL and/or transferrin saturation of ≥ 60%, who received either combination or monotherapy iron chelation agents. Outcome effectiveness was determined by the reduction of serum ferritin level of at least 80%. Safety was analyzed descriptively. A pharmacoeconomic analysis was performed based on clinical outcomes consisting of effectiveness and direct medical costs. Results At the end of the study, serum ferritin was reduced in 34.7% of the combination therapy group and 27.5% of the monotherapy group, however there was no significant difference between the two treatments (P=0.391). Nine (19.5%) patients on combination therapy and 17 (21.2%) patients on monotherapy had adverse drug reaction (ADR), with the most frequently reported ADR was elevated transaminase enzyme levels. Cost minimization analysis revealed that monotherapy for 6 months was IDR 13,556,592.64 less expensive than combination therapy (IDR 44,498,732.07); whereas monotherapy for 12 months was IDR 20,162,836.10 less expensive than combination therapy (IDR 78,877,661.12). Conclusion Combination regimens are as effective as monotherapy regimens in reducing serum ferritin in pediatric β-thalassemia major patients. There is no differences of ADR between combination or monotherapy. The average cost per patient is less expensive with monotherapy compared to combination therapy.
Role of cytogenetic profiles as prognostic factors for complete remission after induction phase in acute myeloblastic leukemia Hikari Ambara Sjakti; Gatot Djajadiman; Pustika Amalia Wahidiyat; Agus Kosasih; Iswari Setianingsih
Paediatrica Indonesiana Vol 61 No 6 (2021): November 2021
Publisher : Indonesian Pediatric Society

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14238/pi61.6.2021.343-9

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Background Risk stratification for acute myeloid leukemia (AML) in children is a must in treatment strategy. This stratification is based on cytogenetic profiles, which are needed to determine proper management to gain better outcomes and reduce side effects of treatment. There is no such risk stratification available in Indonesia until now. Objective To evaluate the association between cytogenetic profiles of t(8,21) and inv(16) mutations with the complete response to induction phase of chemotherapy in pediatric AML. Methods A prospective study was conducted between year 2018 and 2020, involving children with AML from 4 pediatric oncology centers in Jakarta. Subjects were evaluated for cytogenetic profiles, especially t(8,21) and inv(16), as the favorable predictors for AML. Bone marrow remission was evaluated after 2 cycles of induction phase. The results were evaluated for remission rate and survival analysis. Results Karyotype data of 18 subjects were obtained. Translocation t(8;21) detected in 1 subject, and inv(16) mutation in 4 subjects. These two variables had no significant correlation with complete remission after induction phase. Nevertheless, favorable group had more tendencies to achieved remission than unfavorable group. Complete remission achieved in 61% subjects, 90% of theme had a relapse period with an average time 43 weeks. The relapse period in favorable group was shoter than in unfavorable group (34 weeks and 44 weeks, respectively). Conclusions This study shows that cytogenetic profiles of t(8;21) and inv(16) mutation can not be used as prognostic factors for complete remission after induction phase of chemotherapy in pediatric AML.
Deteksi antibodi trombosit spesifik anti-hpa-3 pada neonatus dengan trombositopenia Arum Margi Kusumawardani; Ni Ken Ritchie; Pustika Amalia Wahidiyat
MEDIA ILMU KESEHATAN Vol 10 No 1 (2021): Media Ilmu Kesehatan
Publisher : Universitas Jenderal Achmad Yani Yogyakarta

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30989/mik.v10i1.555

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Background: The immune factor causing thrombocytopenia in neonates can occur even during pregnancy. Antigen discrepancies in the platelet membrane expressed by the fetus and maternal can be the cause of thrombocytopenia. This is due to the presence of anti-platelet antibodies produced by the maternal body as a form of immune response after exposure to antigens on the platelet membrane expressed by the fetus. Human platelet antigen detection has not been carried out in Indonesia, there is no known antigen on the platelets. This allows the occurance of alloimmune thrombocytopenia in neonates, one of sign that can be recognized through clinical symptoms was neonates with thrombocytopenia. Screening anti-platelet antibodies in neonates with thrombocytopenia is an effort to find the possibility of anti-human platelet antigen antibodies. Objective: The aim of this study is to find out the presence of anti-platelet antibodies in neonates with thrombocytopenia. Methods: The study is descriptive observational with cross sectional design. The subject in this study were neonates with thrombocytopenia according to the study criteria. The collected sample is screened for the presence of anti-platelet antibodies, then identification of anti-HPA antibodies. Results: Screening in 30 neonates showed that 3 neonatal positive anti-platelet antibodies, 2 with borderline and 25 negative anti-platelet antibodies. Identification of anti-platelet antibodies was performed in five samples (result of screening, three with positive screening and two borderline), indicating that all were negative for the anti-human platelet antigen antibody GPIIb/IIIa specific HPA-3. Conclusion: Based on the screening result, five samples were found to have anti-platelet antibodies in neonates with thrombocytopenia, but after identification none of them were found to be specific anti-HPA antibodies to GPIIb/IIIa.
Does protein intake correlate with tubular function in very preterm neonates? Henny Adriani Puspitasari; Partini Pudjiastuti Trihono; Pustika Amalia Wahidiyat
Paediatrica Indonesiana Vol 63 No 4 (2023): July 2023
Publisher : Indonesian Pediatric Society

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14238/pi63.4.2023.245-55

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Background High protein intake in very preterm neonates (VPN) is important for growth. However, preterm kidneys have fewer functional nephrons and many of the ones present may be immature. Studies have shown that high protein intake induces nephron hypertrophy, proteinuria, and glomerular sclerosis, which lead to tubular injury. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a biomarker that is released during proximal tubular cell injury. The uNGAL to creatinine (uNGAL/Cr) ratio is commonly performed for normalization. Objective To assess for a possible association between protein intake and uNGAL/Cr ratio in VPN. Methods A prospective cohort study was conducted in two NICUs in Jakarta. Subjects’ urine specimens were collected at 0-48 hours, 72 hours, and 21 days after birth to determine uNGAL/Cr ratio as a biomarker of tubular injury. Protein was administered according to study sites NICU guidelines. Protein intake was recorded daily from 14-21 days of age for formula and measured twice with a human milk analyzer for breast milk. ELISA was used to measure uNGAL concentration. Low protein intake was defined as <3g/kg/day and high protein intake was defined as ?3g/kg/day. Maternal and perinatal variables were recorded from medical records. Results Fifty-nine VPN were recruited, of whom 39 completed the study. Median uNGAL/Cr ratio ranged from 0.32-104.11 ng/mg. The uNGAL/Cr ratio was not correlated with protein intake but was inversely correlated with gestational age and birth weight [r = -0.320, P=0.019 for the 72-hr (T2) urinary collection]. Higher uNGAL/Cr levels were associated with maternal infection [14.4 (range 4.4-104.1) vs 7.2 (range 0.5–32.4) ng/mg, P=0.004 at the 0-48-hr (T1)], maternal anemia [6.9 (range 1.2–66.6) vs 1.7 (range 0.3–89.2) ng/mg, P=0.001 at the 21-day (T3)] and nephrotoxic medication [15.9 (range 1.3–63.8) vs 1.0 (range 0.4–8.6) ng/mg, P=0.026 at the 72-hr]. Conclusion Protein intake according to current nutritional guidelines does not correlate with tubular injury in VPN, as measured by uNGAL/Cr ratio. Maternal infection, maternal anemia, lower birth weight, and nephrotoxic medication, were associated with higher uNGAL/Cr levels in VPN.
Clinical characteristics and genetic mutations in hemophilia A patients with inhibitors Fitri Primacakti; Pustika Amalia Wahidiyat; Damayanti Rusli Sjarif; Novie Amelia Chozie; Ninik Sukartini; Joedo Prihartono; Sheila Claudhea Salsabila; Nadhifa Tazkia Ramadhani; Bidasari Lubis
Paediatrica Indonesiana Vol. 66 No. 1 (2026): January 2026
Publisher : Indonesian Pediatric Society

Show Abstract | Download Original | Original Source | Check in Google Scholar

Abstract

Background Antibodies to factor VIII, known as inhibitors, are a major problem in hemophilia A, especially in severe cases. Certain genetic mutations are associated with a higher risk of the formation of inhibitors. This study is the first in Indonesia to report on genetic mutations of hemophilia A patients with inhibitors. Objectives To detect genetic mutations, investigate potential risk factors, and evaluate inhibitor prevalence in pediatric hemophilia A patients. Methods An observational study was conducted at the Pediatric Hemophilia Treatment Center of Cipto Mangunkusumo Hospital, Jakarta. Inhibitors were measured using the Bethesda assay and classified as low- or high titer. Inverse shifting polymerase chain reaction (IS-PCR) was performed to detect inversion mutations. Negative results for inversion were followed by Sanger sequencing. Clinical data were obtained from medical records. Results Inhibitors were detected in 17 of 114 hemophilia A patients (14.9%), most of whom (88.2%) had severe disease and had fewer than 150 days of exposure to clotting factor concentrates (CFCs), classifying them as previously untreated patients (PUPs). The genetic mutations identified in inhibitor patients were intron 22 inversion (INV-22) mutations (41.2%), intron 1 inversion (INV-1) mutations (29.4%), nonsense mutations (17.6%), large deletions (5.9%), and missense mutations (5.9%). Family history of inhibitors, previous intensive treatment for major bleeding events or surgery, and type of concentrate were potential risk factors. Conclusion Intron 22 inversion mutations were the most common mutations associated with the presence of inhibitors in hemophilia A patients.