Browsing by Author "Weatherall, D. J."

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Emerging insights in the management of hemoglobin E beta thalassemia
(Wiley-Blackwell, 2010) Olivieri, N. F.; Thayalsuthan, V.; O Donnell, A.; Premawardhena, A.; Rigobon, C.; Muraca, G.; Fisher, C.; Weatherall, D. J.
Globally, hemoglobin (Hb) E beta thalassemia accounts for approximately half the severe forms of beta thalassemia. Because of its wide clinical diversity and the ability of patients with this condition to adapt unusually well to low hemoglobin levels, the management of Hb E beta thalassemia, particularly the decision to instigate regular blood transfusion, is particularly difficult. Here, we present a summary of our work in patients with this condition, which attempts to define clinical, adaptive, and genetic factors of possible value in determining the early management of this condition.
Hemoglobin E-[beta] Thalassemia: Progress Report from the International Study Group
(Wiley-Blackwell, 2005) Premawardhena, A.; de Silva, S.; Arambepola, M.; Olivieri, N. F.; Vichinsky, E. P.; Merson, L.; Muraco, G.; Allen, A.; Fisher, C.; Peto, T.; Weatherall, D. J.
A long-term observational study of Hb E-beta-thalassemia in Sri Lanka is beginning to define some of the genetic and environmental factors that are responsible for its remarkable phenotypic variability. In this population there is a very small difference between the steady-state hemoglobin levels between the mild and severe phenotypes, and it has been possible to stop transfusion in many of those who have been on long-term treatment of this kind. These preliminary observations, made over the last 7 years, provide directions for future research into this increasingly important disease.
Identifying haemoglobinopathy traits and iron deficiency in Sri Lanka using the dtchlorophenolindophenol (DCIP) and one- tube osmotic fragility (OF) tests and measurement of red cell zinc protoporphyrin (ZPP)
(Sri Lanka Medical Association., 2019) Perera, P. S.; Premawardhena, A.; Mettananda, S.; Rodrigo, R.; Perera, L.; Weatherall, D. J.; Allen, S.; Allen, A.
INTRODUCTION & OBJECTIVES: Effective, low-cost, point-of-care tests are needed for haemoglobinopathy traits and iron deficiency throughout Southeast Asia. The objective of this study is to evaluate a combination of simple, low cost, easy-to-interpret and rapid tests as a "one-stop" screening procedure for identifying carriers of haemoglobin variants and iron deficiency in Sri Lanka. METHODS: Between November 2017 and May 2018, the KKU-OF and KKU modified DCIP tests (KKU, Thailand) were compared with High Performance Liquid Chromatography (HPLC) in a cross-sectional survey of 1324/1332 (99.4%) children attending secondary schools in Gampaha district, Sri Lanka. Iron deficiency was indicated in children with a raised red cell ZPP (Helena Biosciences), and confirmed by measurement of low serum ferritin and normal C- reactive protein (CRP). RESULTS: Median age was 17 years (IQR 16-18), all were Sinhalese and 814/1324 (61.5%) were female. HPLC identified 26 students with β-thalassaemia trait and 3 with HbE trait. The KKU-OF test correctly identified all 26 students with β-thalassaemia trait (sensitivity=100%) but was also positive in 288 samples with a normal HPLC result (specificity= 1007/1295; 85.5%). The KKU-DCIP test was positive only in the 3 students with HbE (100% sensitive and 100% specific). Iron deficiency was present in 148/1318 (11.2%) students. CONCLUSION: This one-stop approach may be an effective and affordable procedure in screening for haemoglobinopathy traits and identifying iron deficiency. We are investigating the causes of the false positive OF test results and planning large scale studies to assess cost-effectiveness.
Is the beta thalassaemia trait of clinical importance?
(Wiley-Blackwell, 2008) Premawardhena, A.; Arambepola, M.; Katugaha, N.; Weatherall, D. J.
Although the beta thalassaemia trait affects millions of people worldwide, there have been no controlled studies to determine whether it is associated with any clinical disability or abnormal physical signs. To address this question, 402 individuals were studied: 217 with beta thalassaemia trait, of whom 154 were aware of the diagnosis and 63 were unaware until after the completion of the study; 89 normal controls; and 96 controls with mild hypochromic anaemia. There was a significant increase in symptoms ascribable to anaemia and episodes of pyrexia in those with the beta thalassaemia trait that were not influenced by prior knowledge that they had this condition. There was no difference in physical findings, notably splenomegaly, between those with beta thalassaemia trait and either control group
A nationwide survey of hospital-based thalassemia patients and standards of care and a preliminary assessment of the national prevention program in Sri Lanka
(Public Library of Science, 2019) Premawardhena, A.P.; Mudiyanse, R.; de Silva, S.T.; Jiffry, N.; Nelumdeniya, U.; de Silva, U.; Lamabadusuriya, S.P.; Pushpakumara, K.; Dissanayaka, R.; Jansz, M.; Rifaya, I.; Navarathne, U.; Thirukumaran, V.; Arambepola, M.; Bandara, W.D.; Vaidyanatha, U.; Mendis, D.; Weerasekara, K.; de Silva, N**.; Kumara, D.K.S.; Amarasena, S.D.; Hemantha, K. K.; Refai, M.A.C.M.; Silva, I.; Hameed, N.; Rajiyah, F.; Mettananda, S.; Allen, A.; Weatherall, D. J.; Oliveri, N. F.
OBJECTIVES:Our aim was to describe the numbers and distribution of patients with different types of thalassemia and to assess the standards of care in all thalassemia treatment centers throughout Sri Lanka and the success of the ongoing prevention programme.METHODS:This cross-sectional island-wide survey was conducted by two trained medical graduates, who visited each thalassemia center to collect data from every patient, using a standardized form. Data was collected through review of patient registers and clinical records.RESULTS: We collected data on 1774 patients from 23 centers. 1219 patients (68.7%) had homozygous β-thalassemia, 360 patients (20.3%) had hemoglobin E β-thalassemia, and 50 patients (2%) had sickle β-thalassemia. There were unacceptably high serum ferritin levels in almost all centers. The annual number of births of patients with β-thalassaemia varied between 45-55, with little evidence of reduction over 19 years. CONCLUSIONS:Central coordination of the treatment and ultimately prevention of thalassemia is urgently needed in Sri Lanka. Development of expert centers with designated staff with sufficient resources will improve the quality of care and is preferred to managing patients in multiple small units.
Natural history of haemoglobin E/beta thalassaemia: the impact of splenectomy on growth and steady state hemoglobin levels
(American Society of Hematology, 1999) Sharma S.; Premawardhena, A.P.; Fathihu, F.; de Silva, S.; de Silva, L.; Vichinsky, E. P.; Weatherall, D. J.; Olivieri, N. F.
A "One-Stop" screening protocol for hemoglobinopathy traits and iron deficiency in Sri Lanka
(Lausanne : Frontiers Media S.A., 2019) Allen, A.; Perera, S.; Perera, L.; Rodrigo, R.; Mettananda, S.; Matope, A.; Silva, I.; Hameed, N.; Fisher, C. A.; Olivieri, N.; Weatherall, D. J.; Allen, S.; Premawardhena, A.
INTRODUCTION: The high frequencies of carriers of severe haemoglobinopathies and of iron deficiency in Southeast Asia require reliable and affordable tests to improve on current screening procedures. OBJECTIVES: We evaluate a "one stop" approach using the THALCON dichlorophenolindophenol (DCIP) and one-tube osmotic fragility (OF) tests and measurement of Zinc Protoporphyrin (ZPP) to detect and distinguish HbE and β-thalassaemia traits from iron deficiency. We compare findings with current screening practice in Sri Lanka that relies on the identification of low mean red cell volume and/or mean red cell hemoglobin for this purpose.METHODS: Between November 2017 and May 2018, we undertook a cross-sectional survey of secondary school students in Gampaha district, Sri Lanka. The THALCON-DCIP and OF tests were compared to capillary electrophoresis (CE), used as a gold standard to detect haemoglobinopathies. ZPP was measured in whole blood. Plasma ferritin and C-reactive protein (CRP) were measured in students with a raised ZPP concentration. RESULTS: We collected venous blood samples from 1,324/1,332 (99.4%) students. The median age of the students was 17 (IQR 16-18) years, all were Sinhalese and 814/1,324 (61.5%) were female. CE identified 3 students with HbE trait and 26 students with β-thalassaemia trait. The THALCON-DCIP test was positive only in the 3 students with HbE (sensitivity 100%, 95% CI 29.2-100.0; specificity 100%, 95% CI 99.7-100.0). The THALCON-OF test identified all 26 students with β-thalassaemia trait (sensitivity = 100%, 95% CI 86.8-100.0) and 287 students with a normal CE result (specificity = 77.9%; 95% CI 75.5-80.1). It was also positive in 2/3 (66.7%) students with HbE trait. Iron deficiency (ZPP > 70 μmol/mol heme) was present in 118/1,240 (9.5%) students with a normal hemoglobin genotype, all of whom had plasma ferritin <15 ng/ml and CRP <5 mg/L. CONCLUSION: This one-stop approach offers reliable and affordable population screening for both haemoglobinopathy traits and iron deficiency in resource-limited settings where these conditions are common and ensures that iron supplements are targeted only to those who require them. Further work is warranted to refine the OF test to reduce the number of false positive results
Studies in haemoglobin E beta-thalassaemia
(Wiley-Blackwell, 2008) Olivieri, N. F.; Muraca, G. M.; O Donnell, A.; Premawardhena, A.; Fisher, C.; Weatherall, D. J.
Haemoglobin E beta-thalassaemia is the commonest form of severe thalassaemia in many Asian countries, but little is known about its natural history, the reasons for its clinical diversity, or its optimal management. Despite its frequency, haemoglobin E beta-thalassaemia is often managed in an ill-defined and haphazard way, usually by demand transfusion. We studied a cohort of Sri Lankan patients with haemoglobin Ebeta-thalassaemia over 5 years, and identified several genetic and environmental factors possibly contributing to the phenotypic diversity of the disorder. These included modifiers of haemoglobin F production, malaria and age-related changes in adaptation to anaemia. Our findings suggest that in many patients, haemoglobin E beta-thalassaemia can be managed without transfusion, even with low haemoglobin levels. Age-related changes in the pattern of adaptation to anaemia suggest that more cost-effective approaches to management should be explored.