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BACKGROUND: Non-transfusion-dependent ß-thalassaemia (NTDßT) is a subset of inherited haemoglobin disorders characterised by reduced production of the ß-globin chain of haemoglobin leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it may be required to prevent complications of chronic anaemia, such as impaired growth and hypercoagulability. People with NTDßT also experience iron overload due to increased iron absorption from food sources which becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin (HbF) level have been found to require fewer blood transfusions, thus leading to the emergence of treatments that could increase its level. HbF inducers stimulate HbF production without altering any gene structures. Evidence for the possible benefits and harms of these inducers is important for making an informed decision on their use. OBJECTIVES: To compare the effectiveness and safety of the following for reducing blood transfusion for people with NTDßT: 1. HbF inducers versus usual care or placebo; 2. single HbF inducer with another HbF inducer, and single dose with another dose; and 3. combination of HbF inducers versus usual care or placebo, or single HbF inducer. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 21 August 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs comparing single HbF inducer with placebo or usual care, with another single HbF inducer or with a combination of HbF inducers; or comparing different doses of the same HbF inducer. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were blood transfusion and haemoglobin levels. Our secondary outcomes were HbF levels, the long-term sequelae of NTDßT, quality of life and adverse events. MAIN RESULTS: We included seven RCTs involving 291 people with NTDßT, aged two to 49 years, from five countries. We reported 10 comparisons using eight different HbF inducers (four pharmacological and four natural): three RCTs compared a single HbF inducer to placebo and seven to another HbF inducer. The duration of the intervention lasted from 56 days to six months. Most studies did not adequately report the randomisation procedures or whether and how blinding was achieved. HbF inducer against placebo or usual care Three HbF inducers, HQK-1001, Radix Astragali or a 3-in-1 combined natural preparation (CNP), were compared with a placebo. None of the comparisons reported the frequency of blood transfusion. We are uncertain whether Radix Astragali and CNP increase haemoglobin at three months (mean difference (MD) 1.33 g/dL, 95% confidence interval (CI) 0.54 to 2.11; 1 study, 2 interventions, 35 participants; very low-certainty evidence). We are uncertain whether Radix Astragali and CNP have any effect on HbF (MD 12%, 95% CI -0.74% to 24.75%; 1 study, 2 interventions, 35 participants; very low-certainty evidence). Only medians on haemoglobin and HbF levels were reported for HQK-1001. Adverse effects reported for HQK-1001 were nausea, vomiting, dizziness and suprapubic pain. There were no prespecified adverse effects for Radix Astragali and CNP. HbF inducer versus another HbF inducer Four studies compared a single inducer with another over three to six months. Comparisons included hydroxyurea versus resveratrol, hydroxyurea versus thalidomide, hydroxyurea versus decitabine and Radix Astragali versus CNP. No study reported our prespecified outcomes on blood transfusion. Haemoglobin and HbF were reported for the comparison Radix Astragali versus CNP, but we are uncertain whether there were any differences (1 study, 24 participants; low-certainty evidence). Different doses of the same HbF inducer Two studies compared two different types of HbF inducers at different doses over two to six months. Comparisons included hydroxyurea 20 mg/kg/day versus 10 mg/kg/day and HQK-1001 10 mg/kg/day, 20 mg/kg/day, 30 mg/kg/day and 40 mg/kg/day. Blood transfusion, as prespecified, was not reported. In one study (61 participants) we are uncertain whether the lower levels of both haemoglobin and HbF at 24 weeks were due to the higher dose of hydroxyurea (haemoglobin: MD -2.39 g/dL, 95% CI -2.80 to -1.98; very low-certainty evidence; HbF: MD -10.20%, 95% CI -16.28% to -4.12%; very low-certainty evidence). The study of the four different doses of HQK-1001 did not report results for either haemoglobin or HbF. We are not certain if major adverse effects may be more common with higher hydroxyurea doses (neutropenia: risk ratio (RR) 9.93, 95% CI 1.34 to 73.97; thrombocytopenia: RR 3.68, 95% CI 1.12 to 12.07; very low-certainty evidence). Taking HQK-1001 20 mg/kg/day may result in the fewest adverse effects. A combination of HbF inducers versus a single HbF inducer Two studies compared three combinations of two inducers with a single inducer over six months: hydroxyurea plus resveratrol versus resveratrol or hydroxyurea alone, and hydroxyurea plus l-carnitine versus hydroxyurea alone. Blood transfusion was not reported. Hydroxyurea plus resveratrol may reduce haemoglobin compared with either resveratrol or hydroxyurea alone (MD -0.74 g/dL, 95% CI -1.45 to -0.03; 1 study, 54 participants; low-certainty evidence). We are not certain whether the gastrointestinal disturbances, headache and malaise more commonly reported with hydroxyurea plus resveratrol than resveratrol alone were due to the interventions. We are uncertain whether hydroxyurea plus l-carnitine compared with hydroxyurea alone may increase mean haemoglobin, and reduce pulmonary hypertension (1 study, 60 participants; very low-certainty evidence). Adverse events were reported but not in the intervention group. None of the comparisons reported the outcome of HbF. AUTHORS' CONCLUSIONS: We are uncertain whether any of the eight HbF inducers in this review have a beneficial effect on people with NTDßT. For each of these HbF inducers, we found only one or at the most two small studies. There is no information on whether any of these HbF inducers have an effect on our primary outcome, blood transfusion. For the second primary outcome, haemoglobin, there may be small differences between intervention groups, but these may not be clinically meaningful and are of low- to very low-certainty evidence. Data on adverse effects and optimal doses are limited. Five studies are awaiting classification, but none are ongoing.
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Talassemia beta , Humanos , Talassemia beta/terapia , Hemoglobina Fetal , Hidroxiureia , Resveratrol , Transfusão de SangueRESUMO
L-asparaginase is effective as part of the first line childhood acute lymphoblastic leukaemia (ALL) treatment regimen but suffers the risk of antibody production causing immune-mediated sequelae. This article aimed to describe the clinical implication of L-asparaginase hypersensitivity and review the types of antibodies and genetic polymorphisms contributing to it. Clinical or subclinical L-asparaginase hypersensitivity may lead to suboptimum therapeutic effect and jeopardise the clinical outcome in ALL children. Anti-asparaginase antibodies immunoglobulin (Ig)G, IgM and IgE were identified in the L-asparaginase hypersensitivities. Enzyme-linked immunosorbent assay (ELISA) is commonly used to quantify the IgG and IgM levels. The role of IgE in mediating L-asparaginase hypersensitivity is contradictory. Moreover, the presence of antibodies may not necessarily correlate inversely with the L-asparaginase efficacies in some studies. Patients with specific genetic variants have been shown to be more susceptible to clinical hypersensitivity of L-asparaginase. With the advance of technology, gene polymorphisms have been identified among Caucasians using whole-genome or exon sequencing, but the evidence is scanty among Asians. There is lack of pre-clinical study models that could help in understanding the pathophysiological pathway co-relating the gene expression and anti-asparaginase antibody formation. In conclusion, future research studies are required to fill the current gap in understanding the immune mediated reactions towards L-asparaginase upon its administration and its potential impact to the disease outcome.
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Giant cell tumor (GCT) is one of the most common tumors of bone and is the most common precursor of aneurysmal bone cysts (ABC). The clinical behavior of concurrent GCT and ABC can be very aggressive in children. GCT of the ribs, with or without ABC, is rarely seen in children. We report a case of an 8-year-old girl with GCT and associated ABC of the ribs who presented with sudden onset of chest pain and breathlessness due to a hemothorax. The patient was successfully treated by surgical resections and arterial embolization. She has remained well for 4 years after the initial surgery.
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Cistos Ósseos Aneurismáticos/diagnóstico , Neoplasias Ósseas/diagnóstico , Tumor de Células Gigantes do Osso/diagnóstico , Hemotórax/diagnóstico , Angiografia , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Criança , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Costelas/patologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Non-transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non-transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established. OBJECTIVES: To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non-transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews.Date of last search: 30 April 2016. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of hydroxyurea in people with non-transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea. DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments. MAIN RESULTS: No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks.Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference -2.39 (95% confidence interval - 2.8 to -1.98) and mean difference -1.5 (95% confidence interval -1.83 to -1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported.The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well-designed randomised controlled trials with sufficient duration of follow up are recommended.
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Transfusão de Sangue/estatística & dados numéricos , Hematínicos/administração & dosagem , Hidroxiureia/administração & dosagem , Talassemia beta/tratamento farmacológico , Hemoglobina A/análise , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Talassemia beta/sangueRESUMO
Haemoglobin (Hb) Lepore is a variant Hb consisting of two α-globin and two δß-globin chains. In a heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of both patients showed features of thalassaemia intermedia. Other laboratory investigations of the patients showed conflicting results. However, laboratory investigation results of the parents had led to a presumptive diagnosis of compound heterozygote Hb Lepore/ß-thalassaemia and co-inheritance α+-thalassaemia (-α3.7). Hb Lepore has rarely been detected in Southeast Asian countries, particularly in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis, hence appropriate clinical management and genetic counseling.
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Hemoglobinas Anormais/genética , Talassemia alfa/genética , Talassemia beta/genética , Sequência de Bases , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Malásia , Masculino , Dados de Sequência Molecular , Linhagem , Fenótipo , Irmãos , Talassemia alfa/sangue , Talassemia beta/sangueRESUMO
OBJECTIVES: To determine the behavioural impact of chemotherapy in survivors of acute lymphoblastic leukaemia (ALL) treated with chemotherapy only and to identify treatment-related or sociodemography-related factors that might be associated with behavioural outcome. METHODS: We examined 57 survivors of childhood ALL, who were off treatment for at least 2 years and were in remission, aged 4-18 years, and 221 unrelated healthy controls. The Child Behaviour Checklist (CBCL) parent report was used either in English or in Bahasa Malaysia (the national language of Malaysia) to assess the behavioural outcome. RESULTS: Childhood ALL survivors had significantly higher scores on externalising behaviour on the CBCL parent report than did controls. Higher problem scores were found in ALL survivors with single parents on 'total problems' (P = 0.03) and subscales 'withdrawn' (P = 0.03), 'social problems' (P < 0.01) and 'delinquent behaviour' (P = 0.03) than in survivors with married parents. Significant associations were seen between a lower education level of the father and the variables representing internalising (withdrawn, anxious/depressed) and externalising (aggressive behaviour). We observed trends on higher scores in all scales in ALL survivors with single parents than in controls with single parents or with fathers with low education level, especially primary education only. CONCLUSIONS: Malaysian childhood ALL survivors had a significantly increased risk for externalising behavioural problems, and there was a trend towards increased risk of problems in many other behavioural scales. Understanding the sociocultural dimension of patients' health is important to be able to design the most appropriate remedy for problem behaviours detected in this multi-ethnic population.
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Antineoplásicos , Transtornos do Comportamento Infantil , Comportamento Infantil , Pais , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Agressão , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Ansiedade , Estudos de Casos e Controles , Criança , Pré-Escolar , Depressão , Escolaridade , Pai , Feminino , Humanos , Malásia , Masculino , Pais Solteiros , Inquéritos e Questionários , SobreviventesRESUMO
Hb Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] is a rare hemoglobin (Hb) variant due to a mutation at codon 59 of the α2- or α1-globin gene resulting in a glycine to aspartic acid substitution. Two siblings with a unique coinheritance of Hb Adana and Hb Constant Spring (Hb CS, α142, TermâGln, TAA>CAA; HBA2: c.427 T>C) (α(codon 59)α/α(CS)α), were compared phenotypically with another two siblings carrying the Hb Adana mutation and a 3.7 kb deletion (α(codon 59)α/-α(3.7)). Although they all had α-thalassemia intermedia (α-TI), the former were clinically more severe than the latter. The first pair of siblings presented at a much younger age than the second pair and showed lower Hb levels and significant extramedullay hemopoiesis. Another case of a hydropic fetus as a result of Hb H/Hb Adana is also described. Their clinical phenotypes and hematological parameters are all presented for comparison.
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Hemoglobinas Anormais/genética , Heterozigoto , Talassemia alfa/genética , Adolescente , Adulto , Alelos , Substituição de Aminoácidos , Criança , Feminino , Humanos , Malásia , Masculino , Linhagem , Gravidez , Resultado da Gravidez , Irmãos , Adulto Jovem , Talassemia alfa/sangue , Talassemia alfa/diagnósticoRESUMO
Therapeutic drug monitoring of pegylated L-asparaginase (ASNase) ensures the drug effectiveness in childhood acute lymphoblastic leukaemia (ALL) patients. The biological drug property with variable immunogenic host clearance, and the prescription of its generic formulation urge the need for a reliable assay to ensure an optimal treatment and improve outcome. This study aimed to optimise an existing isocratic reversed-phase high performance liquid chromatography (RP-HPLC) method with an automated pre-column sample derivatisation and injection program, and a computational algorithm for measuring serum pegylated ASNase activity in children with ALL. Nath et al.'s method in 2009 was adopted and modified using a pegylated ASNase. A set of Microsoft Excel macros was developed for the serum drug activity computation. An Agilent InfinityLab LC Series 1260 Infinity II Quaternary System with fluorescence detection was employed with an Agilent Poroshell 120 EC-C18 4.6×100â¯mm, 2.7⯵m analytical column. System flow rate was optimised to 2.0â¯mL/min with 40×10-6/bar pump compressibility. The O-phthaldialdehyde (OPA) solution composition was optimised to 1â¯% o-phthaldialdehyde, 0.8â¯% 2-mercaptoethanol, 7.13â¯% methanol, and 1.81â¯% sodium tetraborate. The pre-column derivatisation program mixed 0.1⯵L sample with 25⯵L OPA solution before the automated injection. Method validation was according to the ICH guidelines. Total analysis time was 15â¯min, with L-aspartic acid eluted at 0.96â¯min and internal standard at 4.7â¯min. The calibration curves showed excellent linearity (R ≥0.9999). Interday precision for the drug activity at 0.1 IU/mL, 0.5 IU/mL, and 1 IU/mL were 4.15â¯%, 3.05â¯%, and 3.09â¯% (n = 6). Mean %error for the drug activity at 0.1 IU/mL, 0.5 IU/mL, and 1 IU/mL were 0.90±4.41â¯%, -1.37±3.04â¯%, and -3.03±3.02â¯% (n = 6). Limit of quantitation was 0.03 IU/mL. Majority of the patients' serum drug activity fell within the assay calibration range. Our improved method is automated, having shorter analysis time with a well-maintained separation resolution that enables a high-throughput analysis for application.
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Asparaginase , Monitoramento de Medicamentos , Polietilenoglicóis , Leucemia-Linfoma Linfoblástico de Células Precursoras , Asparaginase/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Criança , Polietilenoglicóis/química , Monitoramento de Medicamentos/métodos , Antineoplásicos/sangue , Reprodutibilidade dos Testes , Cromatografia de Fase Reversa/métodos , CalibragemRESUMO
Kaposi hemangioendothelioma (KHE) is a rare vascular neoplasm that presents usually within the first year of life. Because of its rarity and complexity, there is often a delay in diagnosis. KHE could be associated with a life-threatening consumptive coagulopathy named the Kasabach-Merritt phenomenon (KMP). Here, we present the case of a 2-month-old girl who presented with progressive redness and swelling of her right upper limb over 6 weeks. Multiple health practitioners misdiagnosed her condition as an insect bite, cellulitis, and necrotizing fasciitis and gave treatment accordingly, which proved futile. A full blood count revealed bicytopenia of anemia and thrombocytopenia, a normal coagulation cascade, low fibrinogen, and raised D-Dimer levels. The imaging was suggestive of a high-flow vascular tumor likely to be a KHE. Subsequently, she was started on single-agent oral sirolimus with a dose increment to achieve satisfactory therapeutic levels and was treated for 1 year. She successfully completed the treatment regimen and had only transient hypertriglyceridemia, which resolved upon the completion of treatment. Currently, she is in remission 3 years after treatment. Keeping her case as an example, we would like to highlight the potentially lethal misdiagnosis of KHE with KMP, the importance of an early diagnosis of this condition, and the successful treatment outcome with single-agent sirolimus.
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Objective: Patients with thalassemia major do require lifetime blood transfusions that eventually result in iron accumulation in different organs. We described the usefulness of using magnetic resonance imaging (MRI) T2*imaging values for the evaluation of pancreatic iron load in these patients, and we correlated it with MRI T2* haemosiderosis of the myocardium and liver that has been recognized as a non-invasive assessment of iron overload among patients with thalassemia major. Materials and methods: We conducted a cross-sectional study on 39 patients with thalassemia major in one of the tertiary university hospitals for a 1-year period. Demographic data were collected from the patient's history. MRI T2* of the pancreas, liver, and heart were executed on all patients in the same setting. Objective values of iron overload in these organs were obtained using the MRI post-processing software from online software. Results: A total of 32 (82.1%) patients had pancreatic iron overload including 2 patients (5.1%) with severe iron overload and 15 patients (38.5%) with moderate and mild iron overload, respectively. Nine patients (23.1%) had myocardial iron overload, which included 3 patients (7.7%) who had severe cardiac haemosiderosis. Notably, 37 patients (94.9%) had liver iron overload, which included 15 patients (38.5%) who had severe liver haemosiderosis. There was a moderate positive correlation between the relaxation time of the pancreas and heart haemosiderosis (r = 0.504, P < 0.001). No significant correlation was found between the relaxation time of the pancreas with the liver and the heart with the liver. Conclusion: Pancreatic haemosiderosis precedes cardiac haemosiderosis, which establishes a basis for initiating earlier iron chelation therapy to patients with thalassemia major.
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Optic nerve infiltration as the first sign of isolated central nervous system relapse of acute lymphoblastic leukemia (ALL) is rare. A seven-year-old girl with standard-risk B-cell ALL who was in remission presented with sudden onset of left eye pain and loss of vision. Examination revealed no perception to light in the left eye with positive relative afferent pupillary defect. The optic disc was hyperemic and swollen with total obscuration of the disc margin associated with central retinal artery and vein occlusion. Magnetic resonance imaging of the brain and optic nerve showed left intraorbital optic nerve thickening associated with perineural enhancement and intraconal fat involvement. Lumbar puncture revealed leukemic infiltration with blast cells after a week of eye symptoms, while bone marrow aspiration was negative for malignant cells. A diagnosis of left leukemic optic nerve infiltration with central retinal artery and vein occlusion was made. A high index of suspicion with repeat cerebrospinal fluid sampling is crucial to confirm the diagnosis as vitreous biopsy may fail to reveal infiltrative cells.
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Asparaginase-induced hypertriglyceridemia can have a spectrum of clinical presentations, from being asymptomatic to having life-threatening thrombosis or hyperviscosity syndrome. At present, there is no recommendation on routine lipid monitoring during asparaginase-containing treatment phase, nor a standardized guideline on its management. Two cases are presented here to illustrate the effects of concurrent infection on asparaginase-induced hypertriglyceridemia in patients with high-risk ALL and the use of SMOFlipid infusion as a treatment option in an acute situation.
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OBJECTIVES: The objective of this study is to describe the imaging features of medulloblastoma (MB) and correlate the MR characteristics with the different histological subtype of MB with 2-year survival. MATERIALS AND METHODS: This is a retrospective descriptive study. A total of 29 patients diagnosed with MB from January 2005 to December 2015 were included in this study. The MRI brain and spine studies of these patients were retrieved and reviewed by a pediatric radiologist and a neuroradiologist independently, both blinded from the histological type of the MB. The HPE slides were also retrieved and reviewed by a pathologist. RESULTS: 80% of desmoplastic MB showed the presence of intracranial leptomeningeal seeding and 57.1% of anaplastic MB showed the presence of necrosis. The presence of intracranial leptomeningeal seeding (P = 0.002) and necrosis (P = 0.019) was predictive of the histological subtypes. There is a significant correlation between the enhancement pattern and the 2-year outcome (P = 0.03) with 6 out of 8 patients whose tumors showed minimal enhancement having disease progression within 2 years. A significant correlation was also seen between the presence of necrosis with a poorer outcome (P = 0.03) and between the HPE subtype and 2-year outcome (P = 0.03) with anaplastic MB having the poorest prognosis. CONCLUSION: MR imaging features of intracranial leptomeningeal seeding and the presence of necrosis were correlated with a specific histologic subtype of MB. The enhancement pattern as well as necrosis correlated with 2-year poorer outcome of the disease.
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Background: Congenital infantile fibrosarcoma (CIF) is a rare malignant soft tissue tumor that predominantly occurs in children under 1 year of age. CIF is frequently misdiagnosed with other conditions like hemangioma of infancy, infantile fibromatosis, or kaposiform hemangioendothelioma. Disseminated intravascular coagulopathy (DIVC) is rarely reported to be associated with CIF. Case presentation: We describe an infant who presented with a large mass over the right arm. She was initially treated conservatively as hemangioma but was later confirmed by tissue histopathological examination to have CIF as the mass rapidly increased in size. She developed massive intra-tumoral bleed with DIVC whilst receiving neoadjuvant chemotherapy requiring multiple blood products transfusion. An urgent near-total resection of the tumor was performed in view of life threatening bleeding despite multiple blood transfusions. Post-operatively, she received further adjuvant chemotherapy. Subsequently, she remained in complete remission 32 months off-treatment and has full function of the affected limb. Conclusions: CIF is an important condition to be considered in infant who has large mass over the extremity. DIVC could be associated with large CIF and when it occurs can be life-threatening. Whenever feasible early surgery should be performed in very young patients with large CIF to prevent mortality from bleeding.
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BACKGROUND: Acquired thrombotic thrombocytopenia purpura is very rarely encountered in children. It is often misdiagnosed initially when the condition is not inherited. CASE PRESENTATION: We describe a 3-year-old Malay boy who presented with simple febrile seizure and had no neurological deficit, however, he was found to have microangiopathic hemolytic anemia, thrombocytopenia, and elevated serum lactate dehydrogenase. An ADAMTS13 assay results showed zero activities (0%), and markedly high level of ADAMTS13 inhibitor (93.15 U/mL) confirming the diagnosis of secondary thrombotic thrombocytopenia purpura. He received fresh frozen plasma infusions for 3 days and subsequently his platelet levels normalized. Serial ADAMTS13 assay results showed improvement. He was also given a short course of prednisolone after which the ADAMTS13 activity normalized (> 114%) at the end of prednisolone course. CONCLUSIONS: At presentation, acquired thrombotic thrombocytopenia purpura in a very young child is commonly misdiagnosed as other conditions like idiopathic thrombocytopenic purpura, Evans syndrome, atypical hemolytic-uremic syndrome, or malignancy. ADAMTS13 assay should be performed early when thrombotic thrombocytopenia purpura is suspected as this condition is associated with dire consequences.
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Proteína ADAMTS13/deficiência , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/genética , Pré-Escolar , Humanos , Masculino , Púrpura Trombocitopênica Trombótica/terapiaRESUMO
UNLABELLED: Optic glioma (OPG) accounts for 4-8% of all brain tumors in children. En-block removal of intraorbital tumor is recommended in cases with disfiguring exophthalmos and impaired vision. Surgical resection of intraorbital optic nerve (ON) poses the risks of permanent ptosis and globe atrophy. We present here the case of a 4-year-old boy with exophthalmos and near blindness due to an intraorbital OPG. Despite chemotherapy he showed progressive exophthalmos and vision loss. Bony orbital decompression with ON transection temporally reduced his exophthalmos. OPG resection was required later for recurrence of his exophthalmos secondary to tumor progression. Post operatively, he had preserved oculomotor nerve functions but developed globe ischemia. Unusually, his ischemic globe caused him to have pain and severe photophobia, which later lead to enucleation. Photophobia has been reported in blind patients. Animal models and MRI functional imaging showed activation of trigeminal pathway during photophobia in completely transected ON. However, the exact neuro-ophthalmology pathway requires further study. CONCLUSION: This is the first described case of photophobia after excision of OPG with ON denervation. Photophobia can be a serious side effect that significantly lowers the patient's quality of life.