Journal/Magazine Articles
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This collection contains original research articles, review articles and case reports published in local and international peer reviewed journals by the staff members of the Faculty of Medicine
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Item Hemoglobin E-beta-thalassemia: Progress report from the international study group(Blackwell Publishing, 2005) Premawardhena, A.; de Silver, 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.Item Pitfalls in the diagnosis of β-Thalassemia Intermedia(Informa Healthcare, 2021) Perera, S.; Allen, A.; Rees, DC.; Premawardhena, A.We present case histories of three patients who had β-thalassemia (β-thal) trait with 'unusual severity' managed as β-thal intermedia (β-TI) where the basis of disease severity could not be explained with routine hematological and genetic investigations. The clinical diagnosis of 'thalassemia intermedia' was justifiable as they had a β-thal mutation and disease severity that did not fit in with either β-thal trait or with β-thal major (β-TM). As mutations of α, β, and γ genes could not explain the unusual severity of the disease, further analysis with next-generation sequencing (NGS) for red cell diseases was carried out, which led to the diagnosis of coexisting membranopathies. This case series highlights the inherent difficulty in the diagnosis of β-TI with certainty in some patients where the genetic basis is not clear-cut.Item Alpha thalassaemia and extended alpha globin genes in Sri Lanka(Elsevier-Academic Press, 2013) Suresh, S.; Fisher, C.; Ayyub, H.; Premawardhena, A.; Allen, A.; Perera, A.; Bandara, D.; Olivieri, N.; Weatherall, D.The α-globin genes were studied in nine families with unexplained hypochromic anaemia and in 167 patients with HbE β thalassaemia in Sri Lanka. As well as the common deletion forms of α(+) thalassaemia three families from an ethnic minority were found to carry a novel form of α(0) thalassaemia, one family carried a previously reported form of α(0) thalassaemia, --(THAI), and five families had different forms of non-deletional thalassaemia. The patients with HbE β thalassaemia who had co-inherited α thalassaemia all showed an extremely mild phenotype and reduced levels of HbF and there was a highly significant paucity of α(+) thalassaemia in these patients compared with the normal population. Extended α gene arrangements, including ααα, αααα and ααααα, occurred at a low frequency and were commoner in the more severe phenotypes of HbE β thalassaemia. As well as emphasising the ameliorating effect of α thalassaemia on HbE β thalassaemia the finding of a novel form of α(0) thalassaemia in an ethnic minority, together with an unexpected diversity of forms of non-deletion α thalassaemia in Sri Lanka, further emphasises the critical importance of micro-mapping populations for determining the frequency of clinically important forms of the disease.Item Transfusion-transmitted Hepatitis C: A cluster of cases in transfusion-dependent Thalassaemia patients in Sri Lanka(Blackwell Scientific Publications,, 2020) Perera, S.; Bonsall, D.; Niriella, M.A.; Allen, A.; Peries, A.C.; Nelumdeniya, U.B.; Dissanayake, R.; Silva, I.; de Cesare, M.; Klenerman, P.; Weatherall, D.J.; Roberts, D. J.; Premawardhena, A.P.OBJECTIVES: To report the clinical and virologic epidemiology of a recent epidemic of hepatitis C in thalassaemia patients in Sri Lanka. BACKGROUND: Transfusion-dependent thalassaemia patients remain at risk for hepatitis C virus (HCV). Here, we report a cluster of recent HCV infections in Sri Lankan thalassaemia patients and examine the phylogenetic relationship of viral sequences. METHODS: We conducted two prospective cross-sectional surveys of 513 patients in four Sri Lankan thalassaemia centres in 2014/2015 and re-surveyed one centre in 2016. We screened for anti-HCV antibodies using the CTK Biotech enzyme-linked immunosorbent assay (ELISA) kits and confirmed active infection by reverse transcription-polymerase chain reaction (RT-PCR) for HCV-RNA. HCV genomes were sequenced by unbiased target enrichment. RESULTS: Anti-HCV antibodies were found in 116/513 (22.6%) of patients initially tested. Active hepatitis C infection was found in 26 patients with no cases of active hepatitis B infection. Of 26 patients with HCV, two were infected with genotype 1(a), and the rest had 3(a). In a single centre (Ragama), 122 patients (120 new cases and two previously tested, but negative) were retested for anti-HCV antibodies. 32/122 (26.2%) patients were seropositive. Twenty-three (23/122; 18.8%) of these new cases were confirmed by HCV PCR (all genotype 3[a]). CONCLUSIONS: There is a significant cluster of recent HCV cases in multiply transfused thalassaemia patients in several centres in Sri Lanka. Most of the viruses shared a close phylogenetic relationship. The results are consistent with recent continuing transfusion-transmitted HCV infection. Routine surveillance for HCV of chronically transfused patients is required irrespective of screening of blood products.Item The p.H63D allele of the HFE gene protects against low iron stores in Sri Lanka.(Academic Press, 2019) Allen, A.; Premawardhena, A.; Allen, S.; Rodrigo, R.; Manamperi, A.; Perera, L.; Wray, K.; Armitage, A.; Fisher, C.; Drakesmith, A.; Robson, K.; Weatherall, D.In hereditary hemochromatosis, iron overload is associated with homozygosity for the p.C282Y mutation. A second mutation, p.H63D, occurs at significant frequencies in Europe, North Africa, the Middle East and Asia. Early studies in Sri Lanka indicated that the variant had arisen independently, suggesting that it had been the subject of selective pressure. However, its role in iron absorption is unclear. In a survey of 7526 Sri Lankan secondary school students, we determined hemoglobin genotype and measured red cell indices, serum ferritin, transferrin receptor, iron zinc protoporphyrin and hepcidin. These variables were compared according to the presence or absence of the p.H63D variant in a subset of 1313 students for whom DNA samples were available. Students were classified as having low red cell indices if they had an MCV <80 fl and/or MCH <27 pg. Hetero and/or homozygosity for the p.H63D variant was more common in students with normal than low red cell indices (16.4% and 11.9% respectively; p = 0.019). Iron biomarkers and red cell indices were greater in children with the p.H63D variant than in normal and this was statistically significant for MCV (p = 0.046). Our findings suggest that selective pressure by mild iron deficiency contributes to the high frequencies of the p.H63D variant.Item Haemoglobin variants, iron status and anaemia in Sri Lankan adolescents with low red cell indices: A cross sectional survey(Academic Press, 2018) Rodrigo, R.; Allen, A.; Manamperi, A.; Perera, L.; Fisher, C.A.; Allen, S.; Weatherall, D.J.; Premawardhena, A.Iron deficiency complicates the use of red cell indices to screen for carriers of haemoglobin variants in many populations. In a cross sectional survey of 7526 secondary school students from 25 districts of Sri Lanka, 1963 (26.0%) students had low red cell indices. Iron deficiency, identified by low serum ferritin, was the major identifiable cause occurring in 550/1806 (30.5%) students. Low red cell indices occurred in iron-replete students with alpha-thalassaemia including those with single alpha-globin gene deletions. Anaemia and low red cell indices were also common in beta-thalassaemia trait. An unexpected finding was that low red cell indices occurred in 713 iron-replete students with a normal haemoglobin genotype. It is common practice to prescribe iron supplements to individuals with low red cell indices. Since low red cell indices were a feature of all forms of α thalassaemia and also of iron deficiency, in areas where both conditions are common, such as Sri Lanka, it is imperative to differentiate between the two, to allow targeted administration of iron supplements and avoid the possible deleterious effects of increased iron availability in iron replete individuals with low red cell indices due to other causes such as α thalassaemia.Item Adaptation to anemia in hemoglobin E-beta thalassemia(American Society of Hematology, 2010) Allen, A.; Fisher, C.; Premawardhena, A.; Peto, T.; Allen, S.J.; Arambepola, M.; Thayalsuthan, V.; Olivieri, N.; Weatherall, D.Hemoglobin E beta thalassemia is the commonest form of severe thalassemia in many Asian countries. Its remarkably variable clinical phenotype presents a major challenge to determining its most appropriate management. In particular, it is not clear why some patients with this condition can develop and function well at very low hemoglobin levels. Here, we demonstrate that patients with hemoglobin E beta thalassemia have a significant decrease in the oxygen affinity of their hemoglobin, that is an increased P(50) value, in response to anemia. This may in part reflect the lower level of hemoglobin F in this condition compared with other forms of beta thalassemia intermedia. The ability to right-shift the oxygen dissociation curve was retained across the spectrum of mild and severe phenotypes, despite the significantly higher levels of hemoglobin F in the former, suggesting that efforts directed at producing a modest increase in the level of hemoglobin F in symptomatic patients with this disease should be of therapeutic value.Item 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.Item Thalassemia in Sri Lanka: a progress report(Oxford University Press, 2004) Premawardhena, A.P.; de Silva, S.; Arambepola, M.; Olivieri, N.; Merson, L.; Muraco, J.; Allen, A.; Fisher, C.A.; Peto, T.; Vichinsky, E.; Weatherall, D.J.The thalassemias pose an increasing burden for health-care services in many Asian countries. In order to conserve rare resources, it is essential to determine the reasons for the remarkable phenotypic heterogeneity and natural history of these disorders so that the most cost-effective methods for their control and management can be established. A long-term observational study of patients with different forms of thalassemia in Sri Lanka suggests that in addition to the well-defined primary, secondary and tertiary genetic modifiers, environmental factors, particularly malaria, and variation in the ability to adapt to the profound anaemia which characterizes these conditions, may play a significant role in determining their clinical severity. These findings may have important implications for the control and management of thalassemia in Asian populations