Reviewing the Compounding Risks for Tuberculosis DrugInduced Liver Injury in a Patient with Transfusion Dependent Thalassaemia

@#A patient presents with jaundice three weeks into commencement of anti-tuberculosis therapy (ATT). Tuberculosis drug-induced liver injury (TB-DILI) is a main concern in patients commencing ATT. Studies have reported various risk factors associated with TB-DILI, urging vigilance in monitoring liver enzymes in these patients. We aim to review the causes of jaundice in a patient with transfusion dependent thalassaemia commenced on ATT and highlight the risk factors associated with TB-DILI.

Transfusion Transmitted Malaria in a Thalassaemia Major Patient

@#Blood safety is a major global issue. Transfusion transmitted parasitic infections (TTPI) like malaria are rare and possibly under-reported, a situation which could be attributed to lack of awareness of the mosquito-borne transmission of infection. Such infections are still considered potential health hazards, as they can pose a significant threat especially in immunocompromised patients, where they have proven to be fatal. Prevention of the transmission depends solely on the donor’s questionnaire which addresses previous or current infection with aetiologic agents. Donor deferral is effective however clear guidelines are needed. This case report features the transfusion-transmitted of Plasmodium Falciparum in a 15-year-old splenectomised patient with underlying beta thalassaemia major.

Cutaneous Lesions Among South Indian Children With Beta Thalassaemia Major

Objective: To study the cutaneous lesions among south Indian children with Beta thalassaemia major . Design: Observational, hospital based study. Method & Material: 67 children between age 1 year to 14 years with diagnosis of beta thalassaemia major were followed up at Paediatric hematology clinic over 4 years for cutaneous lesions. Results: The common skin lesions were pruritus(49.2%),xerosis (40%) and hyper pigmentations (37.3%).

The effectiveness of sofosbuvir and daclatasvir in the treatment of hepatitis C in thalassaemia major patients and their effect on haematological factors

Context: Patients with thalassaemia are at risk of infections such as hepatitis C virus (HCV) due to their repeated blood transfusions; meanwhile, the treatment of thalassaemia patients who had developed HCV infection is a controversial issue. Aims: Although the effectiveness of direct-acting antivirals on HCV infection has been confirmed, their side-effects as well as effects on haematological factors due to the resultant need for blood transfusion remain to be further understood. Materials and Methods: In this study, 61 patients with major beta thalassaemia and HCV infection, and who had a history of interferon treatment failure were examined. The patients underwent a 24-week treatment with sofosbuvir (SOF) and daclatasvir (DAC). Sustained virological response 12 was used to assess response to treatment. At the end of the study, the need for blood transfusion and serum ferritin was evaluated. Results: About 98.4% of the patients responded to the treatment, and only one patient with genotype 1b did not respond positively. No significant complications necessitating treatment cessation were observed, and all the patients tolerated the treatment well. The level of liver enzymes showed a significant reduction 12 weeks after the treatment. The need for blood transfusions in patients before treatment was averagely 1.595 ± 0.65 bag per month, in which 1.593 ± 0.64 bags were received after treatment (P = 0.9). This regimen did not affect the amount of anaemia in patients and did not differentiate the need for blood transfusions. The rate of haemoglobin before treatment was 9.5 ± 1.42 g/dl, which reached 9.6 ± 1.6 g/dl after treatment (P = 0.54). Ferritin levels decreased significantly (from 1948.08 ± 1539.54 to 1315.73 ± 1207.67 ng/ml) (P = 0.001) in the patients after the treatment. Conclusion: Combination of SOF and DAC is an effective and tolerable treatment regimen without affect on the amount of anaemia in patients and did not differentiate the need for blood transfusions.

A concurrent parallel study to compare the efficacy and safety of oral iron chelators, defrasirox and defriprone in patients of beta thalassaemia major

Background: This study was planned to evaluate all the cases of ? thalassaemia major, already receiving one of the oral iron chelators for a comparison among the efficacy, safety and economy of deferasirox and deferiprone to establish the better option in an Indian scenario.Methods: We identified two groups of patients: 38 treated with deferasirox and 35 treated with deferiprone. Laboratory parameters such as serum ferritin, creatinine, SGPT, Hb, CBC and urine were recorded at the time of inclusion and at 1, 3 and 6 months after the inclusion. The primary outcome variable was serum Ferritin level at the start and at the end of study. Serum ferritin level was carried out by microparticle enzyme linked immunoassay.Results: Before the study, the mean hemoglobin level was 7.32±1.50mg/dL ranged from 4 to 10.8 in deferasirox group and 7.54±1.15mg/dL ranged from 5.5 to 8.8 in deferiprone group. At the time of inclusion, study population was characterized by a mean serum ferritin value of 4735.11±450.01 SE in deferasirox and 4315.97±340.75 SE in deferiprone group. After one month the mean serum ferritin increases to 4578.66±371.96 in deferasirox and 4388.82±316.16 in deferiprone group. After three month the mean serum ferritin reduces to 4295.60±377.37 in deferasirox and 3988.88±349.84 in Deferiprone group.Conclusions: Thus, we conclude that deferasirox and deferiprone are well tolerated, have few adverse effects and almost have a comparable effect in lowering of the patient's serum ferritin level. Deferiprone is more cost effective but needs a strict control on compliance owing to requirement in three divided doses per day.

Serum Fasting Lipid Profile In Children And Adolescents With -Thalassaemia Major In Southern Pakistan

Objective: Serum fasting lipid profile has been studied in various clinical spectrum of Beta (β)- thalassaemia syndrome. Premature cardiac impairment in thalassaemia major appears primarily due to iron accumulation and oxidative injury; however it might be a sequel of abnormal lipoprotein concentrations. The rational of this study is to analyse the serum fasting lipid profile in cardiovascular disease free β-thalassaemia major (β-TM) patients. Relationships with age, gender, haematological parameters, liver enzymes and serum ferritin were observed. Method: Fasting serum lipid levels, liver function test (LFT), complete blood count (CBC) and serum ferritin were measured in 36 patients with homozygous β-TM from March 2012 to March 2014. Patients were stratified into two groups, age ≤15 and >15 years, to determine the possible lipid profile distinction in relation to age. Results: 17 were males and 19 were females, with median age of 12.0 years. The mean total cholesterol (TC) and triglyceride (TG) were 5.01±1.32 and 8.36±5.28 mmol/L respectively. High TG was detected in 36.1%, while high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL) were markedly low, 0.98±0.51 and 2.35±1.22 mmol/L respectively. No statistically significant difference was noted between the two age groups. The median TC to HDL ratio (TC:HDL) was elevated, 5.7 (4.0). We established significant correlation of total bilirubin with TC (r=-0.4), HDL(r=-0.5) and LDL (r=-0.4) (P<0.05). Conclusion: Dyslipidaemia in β-TM patients is irrespective of age and gender including low HDL and high TC:HDL, whilst high TC:HDL may contribute as a significant risk marker for future cardiac events in these patients.

Prevalence of dentofacial abnormalities in children and adolescents with β-thalassaemia major.

Background: β-thalassaemia major is a hereditary hemolytic anemia and the patients often experience growth retardation, protrusive maxilla, and depressed nasal bride leading to various degrees of malocclusion. Aim: The purpose of this investigation is to find the prevalence of dentofacial abnormalities in β-thalassaemia major patients. Subjects and Methods: Seventy-two patients between 6 and 18 years of age diagnosed with β-thalassaemia major were examined for extraoral abnormalities, malocclusion, oral hygiene, and dental caries. Data obtained were tabulated and statistically analyzed using Chi-square and paired t-test. Results: Thirty-nine (54.2%) were males and 33 (45.8%) were females. Prominent extraoral abnormalities were found in 41 (56.9%) of the individuals. Study population predominantly had class I occlusion (59.7%) followed by class II occlusion (23.6%) and no class III occlusion. Mean oral hygiene index-simplified score was 2.43 ± 1.24, mean decayed missing filled teeth (DMFT) score was 7.10 ± 3.92, and deft was 5.68 ± 3.12. Conclusion: Despite starting regular blood transfusion at an early age, β-thalassaemia major patients showed marked facial abnormalities. When compared with individuals with no systemic disease, oral hygiene status was similar, but the caries experience was higher in β-thalassaemia major patients. Therefore, emphasis to educate these patients in the prevention and control of dental caries and maintenance of good oral hygiene should be considered.

Chelation therapy with desferrioxamine does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in malaysian Chinese β-thalassaemia major patients / La terapia de quelación con deferoxamina no normaliza los niveles de ferritinaa pero atenúa el daño oxidativo y mejora el nivel antioxidante total en los pacientes sinomalayos que padecen de talasemia β

Beta-thalassaemia major causes severe anaemia and patients with it may be transfusion-dependent for life. Regular blood transfusions cause iron-overload that leads to oxidative damage which can hasten mortality. The objective of this research was to study the oxidant-antioxidant indices in β-thalassaemia major patients at the University of Malaya Medical Centre (UMMC) who were on desferrioxaminechelation or without chelation therapy. Blood was collected from 39 Chinese patients and 20 controls. Plasma and peripheral blood mononuclear cell lysates (PBMC) were extracted and biochemical tests to evaluate oxidative stress were performed. Oxidative stress was evident in these patients as advanced oxidized protein products (AOPP) and lipid hydroperoxides were elevated, whereas glutathione peroxidase activity and the ferric reducing antioxidant power (FRAP) were reduced. The catalase activity in the patients' PBMC was elevated, possibly as a compensatory mechanism for the reduced glutathione peroxidase activity in both red blood cells and PBMC. The lower FRAP and higher AOPP levels in the non-chelated patients compared with the chelated patients were indicative of a lower oxidative stress level in the chelated patients. The ferritin levels in the chelated and non-chelated patients were high and the mean levels of liver enzyme activities in the majority of patients were elevated regardless of chelation therapy. In conclusion, this study indicates that desferrioxamine chelation therapy does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in Malaysian Chinese β-thalassaemia major patients.

La beta-talasemia mayor causa anemia severa, y los pacientes con este padecimiento pueden hacerse dependientes de las transfusiones de sangre por el resto de sus vidas. Las transfusiones regulares de sangre dan lugar a una sobrecarga de hierro que conduce al dano oxidativo, el cual a su vez puede acelerar la mortalidad. El objetivo de esta investigación fue estudiar las tasas de oxidantesantioxidantes en pacientes de beta-talasemia mayor en el Centro Médico de la Universidad de Malaya, tanto aquellos bajo tratamiento de quelación con deferoxamina, como aquellos sin terapia de quelación alguna. Se recogieron muestras de sangre de 39 pacientes chinos y 20 controles. Se extrajeron plasma y lisados de celulas mononucleares perifericas (CMSP), y se realizaron pruebas bioquimicas para evaluar el estrés oxidativo. El estrés oxidativo era evidente en estos pacientes en forma de productos avanzados de oxidación de proteinas (PAOP), y los hidroperoxidos de lipidos eran elevados, en tanto que la actividad de glutatión peroxidasa y el poder reductor ferrico/antioxidante (FRAP) era reducida. La actividad de la catalasa en los pacientes de CMSP era elevada, posiblemente como un mecanismo compensatorio frente a la actividad de glutatión peroxidasa reducida tanto en los globulos rojos como en las CMSP. Los niveles más bajos de FRAP y los más altos de PAOP en los pacientes no quelados en comparación con los pacientes quelados, indicaban un bajo nivel de estrés oxidativo en los pacientes quelados. Los niveles de ferritina tanto en los pacientes quelados como en los no quelados, eran altos, y los niveles promedio de actividades enzimaticas del higado fueron elevados en la mayoria de los pacientes, independientemente de la terapia de quelación. En conclusión, este estudio indica que la terapia de quelación con deferoxamina no normaliza el nivel de ferritina, pero en cambio atenua el daño oxidativo, y mejora el nivel antioxidante total en los pacientes sinomalayos afectados por la betatalasemia mayor.

Influence of therapy compliance on the prognosis of children with thalassaemia major / 中国实用护理杂志

Objective The purpose of this study was to describe the influence of therapy compliance on prognosis of children with thalassaemia major (TM). Methods Children with TM was recruited by convenient sampling. The therapy compliance was measured by compliance index (CI) and serum ferritin (SF), The correlation between therapy compliance and incidence of complications were studied. Results Low therapy compliance existed in children with TM, 22.12% (CI) and 55.77% (SF). But no statistical difference existed in therapy compliance between boys and girls (P>0.05). Complication incidence in children with low therapy compliance was 85.19% (CI) and 100.00% (SF). The incidence of cardiac complication was 60.49% (CI) and 84.78% (SF), hepatic complication was 46.91% (CI) and 76.09% (SF), infectious complication was 8.64% (CI) and 10.86% (SF), growth retardation complication was 55.56% (CI) and 67.39% (SF), anemia complication was 43.21% (CI) and 21.74% (SF). The incidence rate of complications was lower in children with better therapy compliance than those with worse therapy compliance (P<0.01). Conclusions Children with TM had low therapy compliance and high incidence rate of complications. Low therapy increased the incidence rate of complications.