Background Thalassaemia is a chronic disease without an effective cure in a majority. The clinical management has improved considerably during recent years; however, minimal attempts are made to up lift the quality of life among patients, especially in developing countries. Here we aim to describe and compare and to determine factors associated with health related quality of life among patients with transfusion dependent β-thalassaemia major and haemoglobin E β-thalassemia in Sri Lanka. Methods A case control study was conducted in the three largest thalassaemia centres of Sri Lanka. All patients with transfusion dependent β-thalassaemia (β-thalassaemia major and haemoglobin E β-thalassaemia) aged 5–18 years were recruited as cases whilst a randomly selected group of children without chronic diseases were recruited as controls. Socio-demographic and clinical data were collected using an interviewer-administered questionnaire and health related quality of life was measured using the validated Paediatric Quality of Life Inventory Version 4.0. Results Two hundred and seventy one patients with transfusion dependent β-thalassaemia (male-49.1%; mean age- 10.9 ± 3.6 years) and 254 controls (male-47.2%; mean age- 10.4 ± 3.5 years) were recruited. Mean health-related quality of life scores were significantly lower in patients compared to controls (72.9 vs. 91.5, p < 0.001). Of the patients, 224 (84%) had β-thalassaemia major and 43 (16%) had haemoglobin E β-thalassaemia. Quality of life scores in psychological health ( p < 0.05), emotional functioning ( p < 0.05) and social functioning ( p < 0.05) were significantly lower in patients with haemoglobin E β-thalassaemia compared to β-thalassaemia major. Splenectomy ( p < 0.05), short stature ( p < 0.05), under nutrition ( p < 0.05) and longer hospital stays ( p < 0.05) were significantly associated with lower quality of life scores. Conclusions Despite improvements in management, the quality of life among patients with β-thalassaemia still remains low. This is more pronounced in the subset of patients with haemoglobin E β-thalassaemia. Splenectomy, short stature, undernutrition and longer hospital stays were significantly associated with poor quality of life. It is timely, even in developing countries, to direct emphasis and to take appropriate steps to improve standards of living and quality of life of patients with β-thalassaemia.
Hydroxyurea is an antimetabolite drug that induces fetal haemoglobin in sickle cell disease. However, its clinical usefulness in β-thalassaemia is unproven. We conducted a randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of hydroxyurea in transfusion-dependent β-thalassaemia. Sixty patients were assigned 1:1 to oral hydroxyurea 10–20 mg/kg/day or placebo for 6 months by stratified block randomisation. Hydroxyurea treatment did not alter the blood transfusion volume overall. However, a significantly higher proportion of patients on hydroxyurea showed increases in fetal haemoglobin percentage (89% vs. 59%; p < 0.05) and reductions in erythropoietic stress as measured by soluble transferrin receptor concentration (79% vs. 40%; p < 0.05). Based on fetal haemoglobin induction (> 1.5%), 44% of patients were identified as hydroxyurea-responders. Hydroxyurea-responders, required significantly lower blood volume (77 ± SD27ml/kg) compared to hydroxyurea-non-responders (108 ± SD24ml/kg; p < 0.01) and placebo-receivers (102 ± 28ml/kg; p < 0.05). Response to hydroxyurea was significantly higher in patients with HbE β-thalassaemia genotype (50% vs. 0%; p < 0.01) and Xmn1 polymorphism of the γ-globin gene (67% vs. 27%; p < 0.05). We conclude that oral hydroxyurea increased fetal haemoglobin percentage and reduced erythropoietic stress of ineffective erythropoiesis in patients with transfusion-dependent β-thalassaemia. Hydroxyurea reduced the transfusion burden in approximately 40% of patients. Response to hydroxyurea was higher in patients with HbE β-thalassaemia genotype and Xmn1 polymorphism of the γ-globin gene.
IntroductionDespite being one of the first diseases to be genetically characterised, β-thalassaemia remains a disorder without a cure in a majority of patients. Most patients with β-thalassaemia receive only supportive treatment and therefore have a poor quality of life and shorter life spans. Hydroxyurea, which has shown to induce fetal haemoglobin synthesis in human erythroid cells, is currently recommended for the treatment of sickle cell disease. However, its clinical usefulness in transfusion-dependent β-thalassaemia is unclear. Here, we present a protocol for a randomised double-blind controlled clinical trial to evaluate the efficacy and safety of oral hydroxyurea in transfusion-dependent β-thalassaemia.Methods and analysisThis single-centre randomised double-blind placebo-controlled clinical trial is conducted at the Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Adult and adolescent patients with haematologically and genetically confirmed transfusion-dependent β-thalassaemia are enrolled and randomised into the intervention or control group. The intervention group receives oral hydroxyurea 10–20 mg/kg daily for 6 months, while the control group receives a placebo which is identical in size, shape and colour to hydroxyurea without its active ingredient. Transfused blood volume, pretransfusion haemoglobin level, fetal haemoglobin percentage and adverse effects of treatment are monitored during treatment and 6 months post-treatment. Cessation or reduction of blood transfusions during the treatment period will be the primary outcome measure. The statistical analysis will be based on intention to treat.Ethics and disseminationEthical approval has been obtained from the Ethics Committee of Faculty of Medicine, University of Kelaniya (P/116/05/2018) and the trial is approved by the National Medicinal Regulatory Authority of Sri Lanka. Results of the trial will be disseminated in scientific publications in reputed journals.Trial registration numberSLCTR/2018/024; Pre-results.
Background Regular blood transfusion therapy still remains the cornerstone in the management of β‐thalassemia. Although recommendations are clear for patients with β‐thalassemia major, uniform transfusion guidelines are lacking for patients with hemoglobin E β‐thalassemia. In this study, we aim to describe the adequacy, trends, and determinants of blood transfusion therapy in a large cohort of pediatric patients with β‐thalassemia major and hemoglobin E β‐thalassemia. Methods/procedure This cross‐sectional study was performed among all regularly transfused patents with β‐thalassemia aged 2 to 18 years attending three large thalassemia centers in Sri Lanka. Data were collected using an interviewer‐administered questionnaire, perusal of clinical records, and physical examination of patients by trained doctors. Results A total of 328 patients (male 47%) were recruited; 83% had β‐thalassemia major, whereas 16% had hemoglobin E β‐thalassemia. Sixty‐one percent of patients had low pretransfusion hemoglobin levels (< 9.0 g/dL) despite receiving high transfusion volumes (> 200 mL/kg/year) by a majority (56%). Median pretransfusion hemoglobin was significantly lower in patients with hemoglobin E β‐thalassemia compared with β‐thalassemia major (P < 0.001); however, there was no difference in requirement for high transfusion volumes over 200 mL/kg/year in both groups (P = 0.14). Hepatomegaly and splenomegaly were more common in hemoglobin E β‐thalassemia and were associated with lower pretransfusion hemoglobin. Transfusion requirements were higher among patients with hepatitis C and in those who are underweight. Conclusions Over 60% of regularly transfused patients with β‐thalassemia have low pretransfusion hemoglobin levels despite receiving large transfusion volumes. Patients with hemoglobin E β‐thalassemia are undertransfused and specific recommendations should be developed to guide transfusions in these patients.
IntroductionAnaemia in women during pregnancy and child bearing age is one of the most common global health problems. Reasons are numerous, but in many cases only minimal attempts are made to elucidate the underlying causes. In this study we aim to identify aetiology of anaemia in women of child bearing age and to determine the relative contributions, effects and interactions of α- and β-thalassaemia in a region of the world where thalassaemia is endemic.MethodsA cross sectional study was conducted at the Colombo North Teaching Hospital of Sri Lanka. The patient database of deliveries between January 2015 and September 2016 at University Obstetrics Unit was screened to identify women with anaemia during pregnancy and 253 anaemic females were randomly re-called for the study. Data were collected using an interviewer-administered questionnaire and haematological investigations were done to identify aetiologies.ResultsOut of the 253 females who were anaemic during pregnancy and were re-called, 8 were excluded due to being currently pregnant. Of the remaining 245 females, 117(47.8%) remained anaemic and another 22(9.0%) had non-anaemic microcytosis. Of anaemic females, 28(24.8%) were iron deficient, 40(35.4%) had low-normal serum ferritin without fulfilling the criteria for iron deficiency,18(15.3%) had β-haemoglobinopathy trait and 20(17.0%) had α-thalassaemia trait. Of females who had non-anaemic microcytosis, 14(66.0%) had α-thalassaemia trait. In 4 females, both α- and β-thalassaemia trait coexist. These females had higher levels of haemoglobin (p = 0.06), MCV (p<0.05) and MCH (p<0.01) compared to individuals with only β-thalassaemia trait. A significantly higher proportion of premature births (p<0.01) and lower mean birth weights (p<0.05) were observed in patients with α-thalassaemia trait.ConclusionsNearly one third of anaemic females in child bearing age had thalassaemia trait of which α-thalassemia contributes to a majority. Both α- and β-thalassaemia trait can co-exist and have ameliorating effects on red cell indices in heterozygous states. α-Thalassaemia trait was significantly associated with premature births and low birth weight. It is of paramount importance to investigate the causes of anaemia in women of child bearing age and during pregnancy in addition to providing universal iron supplementation.
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