Browsing by Author "Premawardhena, A."

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Acute on chronic osteomyelitis due to coliforms in a Sri Lankan child with homozygous sickle cell disease
(Sri Lanka College of Paediatricians, 2021) Hoole, T.J.; Arunath, V.; de Silva, M.H.A.D.; Muthukumarana, O.G.W.; Kumarasiri, I.M.; Rathnasiri, G.B.A.M.R.; Mahendra, G.; Premawardhena, A.; Mettananda, S.
No Abstract Available
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.
Age-related changes in adaptation to severe anemia in childhood in developing countries
(National Academy of Sciences, 2007) O Donnell, A.; Premawardhena, A.; Arambepola, M.; Allen, S.J.; Peto, T.E.; Fisher, C.A.; Rees, D.C.; Olivieri, N.F.; Weatherall, D.J.
Severe forms of anemia in children in the developing countries may be characterized by different clinical manifestations at particular stages of development. Whether this reflects developmental changes in adaptation to anemia or other mechanisms is not clear. The pattern of adaptation to anemia has been assessed in 110 individuals with hemoglobin (Hb) E beta-thalassemia, one of the commonest forms of inherited anemia in Asia. It has been found that age and Hb levels are independent variables with respect to erythropoietin response and that there is a decline in the latter at a similar degree of anemia during development. To determine whether this finding is applicable to anemia due to other causes, a similar study has been carried out on 279 children with severe anemia due to Plasmodium falciparum malaria; the results were similar to those in the patients with thalassemia. These observations may have important implications both for the better understanding of the pathophysiology of profound anemia in early life and for its more logical and cost-effective management.
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.
Anaemia among females in child-bearing age: Relative contributions, effects and interactions of α- and β-thalassaemia.
(Public Library of Science, 2018) Mettananda, S.; Suranjan, M.; Fernando, R.; Dias, T.; Mettananda, C.; Rodrigo, R.; Perera, L.; Gibbons, R.; Premawardhena, A.; Higgs, D.
INTRODUCTION: Anaemia 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. METHODS: A 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. RESULTS: Out 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. CONCLUSIONS: Nearly 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.
Anaemia among women of child-bearing age: Contributions of alpha and beta-thalassaemia
(Sri Lanka Medical Association, 2018) Mettananda, S.; Suranjan, P.D.M.; Fernando, V.R.; Dias, T.D.; Rodrigo, R.; Perera, L.; Mettananda, K.C.D.; Gibbons, R. J.; Premawardhena, A.; Higgs, D. R.
INTRODUCTION AND OBJECTIVES: Anaemia during pregnancy is attributed to iron deficiency and pregnant women prescribed iron supplements without investigating for a cause. However, aetiology can be diverse and iron efficiency may contribute only partly. We aimed to describe the aetiology of anaemia among women of child bearing age. METHODS: This descriptive study was conducted at Teaching Hospital, Ragama from June-December 2017. Patient database of deliveries between January 2015 and September 2016 at University Obstetrics Unit was screened (n=3636) to identify women with anaemia (haemoglobin
Anaemia in Sri Lanka: the missing pieces
(Sri Lanka Medical Association, 2018) Premawardhena, A.; Perera, P. S.
No abstract available
The association between steatosis and liver damage in transfusion-dependent beta thalassaemia patients
(Wiley-Blackwell, 2023) Padeniya, P.; Ediriweera, D.; de Silva, A.P.; Niriella, M.; Premawardhena, A.
Non-alcoholic fatty liver disease (NAFLD) is a global health problem. Iron is the leading cause of liver damage in patients with transfusion-dependent thalassaemia (TDT), and data on the contribution of NAFLD to liver damage in TDT is lacking. Forty-five heavily transfused TDT patients who did not have biochemical or ultrasonic evidence of liver cirrhosis were evaluated for effects of iron overload, including the presence of diabetes mellitus, hypogonadism, serum ferritin, R2-MRI-liver, and liver enzymes alanine aminotransferase and aspartate aminotransferase. Liver fibrosis and steatosis were estimated using transient elastography (TE). Nine (20%) patients had significant steatosis (S1), and their body mass index (BMI) and liver fibrosis scores were higher than in patients without significant steatosis (S0) (p = 0.03 and p = 0.004, respectively). On regression analysis, the controlled attenuation parameter (CAP) score (i.e., degree of liver steatosis) was associated only with increasing BMI. The TE score (i.e., degree of liver fibrosis) was associated with increasing age, CAP score, male gender, and presence of diabetes. Neither liver steatosis nor fibrosis showed significant association with the liver iron concentration or iron-related organ damage (hypogonadism). In this cohort of TDT patients, steatosis of the liver, which is associated with increasing BMI, appeared to increase the risk of liver fibrosis.
Association of GDF15 levels with body mass index and endocrine status in β-Thalassaemia
(Blackwell Publishing, 2023) Karusheva, Y.; Petry, C.J.; Yasara, N.; Kottahachchi, D.; Premawardhena, A.; Barker, P.; Burling, K.; Sattar, N.; Welsh, P.; Mettananda, S.; O'Rahilly, S.S.
OBJECTIVE: GDF15 has emerged as a stress-induced hormone, acting on the brain to reduce food intake and body weight while affecting neuroendocrine function. Very high GDF15 levels are found in thalassaemia, where growth, energy balance and neuroendocrine function are impaired. We examined the relationships between GDF15 and anthropometric measures and endocrine status in β-thalassaemia. DESIGN: Cross sectional study PATIENTS: All β-thalassaemia patients attending the thalassaemia unit of Colombo North Teaching Hospital for blood transfusions. MEASUREMENTS: Anthropometric data, appetite scores, circulating GDF15, IGF, thyroid and reproductive hormone levels in 103 β-thalassaemia patients were obtained. RESULTS: GDF15 levels were markedly elevated in thalassaemia patients (24.2 fold with β-thalassaemia major compared with healthy controls). Among patients with β-thalassaemia major, the relationship between GDF15 and Body Mass Index (BMI) was curvilinear with all individuals with GDF15 levels above 24,000 pg/ml having a BMI below 20 kg/m2 . After adjustment for BMI, age and Tanner stage, serum IGF1 concentrations correlated negatively with GDF15 in all thalassaemia patients (β=-0.027, p=0.02). We found a significant positive relationship between GDF15 and gonadotropin (in both sexes) and testosterone (in males). CONCLUSIONS: GDF15 levels were markedly elevated in patients with β-thalassaemia and its association with BMI is consistent with the known effect of GDF15 to reduce body weight. The inverse association between GDF15 with IGF1 levels may reflect a neuroendocrine impact of GDF15 or an indirect effect via impaired nutritional state. The positive association with testosterone in males and gonadotropins in both sexes, was surprising and should prompt further GDF15 studies on the hypothalamic pituitary gonadal axis. This article is protected by copyright. All rights reserved.
Blindness and autonomic instability following russell’s viper bite - A case report.
(The Sri Lanka Medical Association, 2022) Francis, K.R.; Jayamanne, S.; Premawardhena, A.
Autonomic instability is a rare complication following elapid bites. Blindness too is a rare complication following Russell’s viper bite and is most likely due to cerebral infarction or direct ocular toxicity. We report a case of a young male from Sri Lanka who developed both transient blindness and autonomic instability following severe envenomation by a Russell’s viper bite.
Blood transfusion therapy for β-thalassemia major and hemoglobin E β-thalassemia: adequacy, trends, and determinants in Sri Lanka.
(John Wiley, 2019) Mettananda, S.; Pathiraja, H.; Peiris, R.; Wickramarathne, N.; Bandara, D.; de Silva, U.; Mettananda, C.; Premawardhena, A.
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.
Body iron status of children with transfusion dependent thalassaemia: Trends of serum ferritin and associations of optimal body iron control
(Sri Lanka Medical Association, 2018) Suriapperuma, T. N. P.; Peiris, K. R. R.; Mettananda, K.C.D.; Premawardhena, A.; Mettananda, S.
INTRODUCTION AND OBJECTIVES: Iron overload due to regular transfusions is one of the most troublesome complications ofthalassaemia. Here we aim to describe body iron status, trends of serum ferritin and associations of optimal body iron control among patients with transfusion dependent thalassaemia. METHODS: A cross sectional descriptive study was conducted at Paediatric and Adolescent Thalassaemia Centres of Colombo North Teaching Hospital from October to December 2017. All children with transfusion dependent thalassaemia aged 16 years and below attending for blood transfusions were recruited. Data was collected using an interviewer-administered questionnaire by interviewing patients and perusing medical records and analysed using SPSS. Ethical approval was obtained from Ethics Committee of University of Kelaniya. RESULTS: Fifty-four children were recruited; 52% were males. Age groups were; <2 years:3.7%, 2-5 years:9.3%,6-10 years:29.6% and 11-16 years:57.4%. Majority (80%) were diagnosed with thalassaemia within the first year of life; 83% had thalassaemia major while 13% had HbE/thalassaemia. Serum ferritin levels were;4999ng/ml:3.7%. Trend of mean serum ferritin at yearly intervals showed gradual rise until 5 years and plateauing thereafter. Children with serum ferritin Rs.25000/=) was significantly associated with optimal body iron control (OR-4.81;95%Cll.17-19.67; p<0.05).CONCLUSION: Mean serum ferritin level gradually rose until 5-years of age and plateaued off in this sample. Optimal body iron control was positively associated with older age at diagnosis of thalassemia and higher family income.
Body iron status of children and adolescents with transfusion dependent β-thalassaemia: trends of serum ferritin and associations of optimal body iron control
(Biomed Central, 2018) Suriyapperuma, T.; Peiris, R.; Mettananda, C.; Premawardhena, A.; Mettananda, S.
OBJECTIVE: This cross sectional study aims to describe the body iron status, trends of serum ferritin and associations of optimal body iron control in patients aged below 16 years with transfusion dependent β-thalassaemia attending Paediatric and Adolescent Thalassaemia Centres of the Colombo North Teaching Hospital of Sri Lanka. RESULTS: Out of 54 children, 51% were males and a majority were aged 11-16 years; 83% had β-thalassaemia major while 13% had HbE β-thalassaemia. Mean serum ferritin was 1778(± 1458) µg/l and 29% had optimal serum ferritin (below 1000 µg/l). Trend of mean serum ferritin over time showed gradual decline between 2011 and 2017 and longitudinal trend of individual patients at yearly intervals showed gradual rise until 5 years of age and plateauing thereafter. All except two patients were receiving iron chelator medication of which the most commonly used was oral deferasirox (92%). The most common iron-related complications were short stature (24.1%) and pubertal delay (42.8% of > 14 years). None of the patients had hypothyroidism, hypoparathyroidism or diabetes. Optimal serum ferritin levels were significantly associated with the diagnosis of thalassaemia at a later age (23.6 vs 9.0 months) and higher family income (OR-4.81;95%CI 1.17-19.67) however was not associated with the age of the patient or duration of transfusion.
Clinical and molecular heterogeneity among Beta Thalassaemia Intermedia in Sri Lanka
(Sri lanka Medical Association, 2015) Perera, P.S.; Silva, D.P.S.I.; Hapugoda, M.; Wickramarathne, M.N.; Wijesiriwardena, I.; Efremov, D.G.; Fisher, C.A.; Weatherall, D.J.; Premawardhena, A.
INTRODUCTION AND OBJECTIVES: Patients with beta thalassaemia intermedia (Tl) unrelated to haemoglobin E/beta thalassaemia account for an important minority in thalassaemia clinics in Sri Lanka. We investigated the genotypic/phenotypic diversity of this small group of patients. METHOD: Fifty Tl patients identified from five thalassaemia centers were clinically assessed and divided in to severity groups based on agreed criteria. Genetic analysis was done by PCR based techniques. RESULTS: There were 26 mild, 12 moderate and 12 in the severe groups. Ages ranged from 5-65 years. Mean haemoglobin of the whole group was 7.8g/dl. Age at presentation ranged from 3 months - 57 years (mean 16.8yrs) and varied according to severity; 17.8 years in mild to 4.8 years in severe group. 86% were on intermittent transfusions whilst 14% were never transfused. Mean total transfusion load in the three groups ranged from 6, 28 to 89. Majority (60%) had splenomegaly and 12% were splenectomised. The median spleen size of each severity group was 0, 4.5 and 7.5 cm respectively. Thalassaemicfacial features were not_ demonstrable in the majority (86%). Genetic analysis identified the commonest mechanism for Tl to be coexistence of a single beta mutation with excess alpha genes (56%). None of these patients had severe phenotype. Coexistence of two beta mutations with alpha thalassaemia invariably gave rise to severe phenotype. Other mechanisms gave rise to varying disease severity. CONCLUSION: This study highlights the remarkable phenotypic variations in beta Tl in Sri Lanka and identifies some genetic mechanisms which can explain this variation.
Comparison of liver MRI R2(FerriScan®) VS liver MRI T2* as a measure of body iron load in a cohort of Beta Thalassaemia major patients
(BioMed Central, 2020) Padeniya, P.; Siriwardana, S.; Ediriweera, D.; Samarasinghe, N.; Silva, S.; Silva, I.; Ahamed, N.; Niriella, M.A.; Premawardhena, A.
ABSTRACT: To compare the similarity of the non-patented T2* and the high cost patented R2 (Ferriscan®) MRI techniques in the measurement of liver iron concentration (LIC) in heavily transfused patients with thalassaemia major in a real- life Sri Lankan hospital setup. We compared LIC measured by MRI, obtained 2 weeks apart, using both T2* and R2 techniques in 15 patients with beta thalassaemia major. They all had a history of > 100 units of blood transfusions life long and also a history of sub optimal chelation. MRI R2 and MRI T2* scan values showed a negative correlation (co-rrelation coefficient = - 0.63, p = 0.01) This correlation was strong in lower LICs and progressively decreased with upper LIC values. Thus a significant discrepancy was observed between median values of two MRI technologies (p = 0.0005) with T2* tending to underestimate iron overload especially in those with very high LIC identified by R2. The lack of concordance of T2* and R2 especially in those with very high reading on R2 suggest the potential errors in interpretations that can occur in "non-expert centres"; which are likely to lead to errors in clinical judgement on the intensity of chelation therapy needed. KEYWORDS: FerriScan®; Iron overload; Liver iron concentration; MRI; T2* scan.
A Comprehensive review of hydroxyurea for β-haemoglobinopathies: the role revisited during COVID-19 pandemic
(BioMed Central,, 2021) Yasara, N.; Premawardhena, A.; Mettananda, S.
BACKGROUND: Hydroxyurea is one of the earliest drugs that showed promise in the management of haemoglobinopathies that include β-thalassaemia and sickle cell disease. Despite this, many aspects of hydroxyurea are either unknown or understudied; specifically, its usefulness in β-thalassaemia major and haemoglobin E β-thalassaemia is unclear. However, during COVID-19 pandemic, it has become a valuable adjunct to transfusion therapy in patients with β-haemoglobinopathies. In this review, we aim to explore the available in vitro and in vivo mechanistic data and the clinical utility of hydroxyurea in β-haemoglobinopathies with a special emphasis on its usefulness during the COVID-19 pandemic. MAIN BODY: Hydroxyurea is an S-phase-specific drug that reversibly inhibits ribonucleoside diphosphate reductase enzyme which catalyses an essential step in the DNA biosynthesis. In human erythroid cells, it induces the expression of γ-globin, a fetal globin gene that is suppressed after birth. Through several molecular pathways described in this review, hydroxyurea exerts many favourable effects on the haemoglobin content, red blood cell indices, ineffective erythropoiesis, and blood rheology in patients with β-haemoglobinopathies. Currently, it is recommended for sickle cell disease and non-transfusion dependent β-thalassaemia. A number of clinical trials are ongoing to evaluate its usefulness in transfusion dependent β-thalassaemia. During the COVID-19 pandemic, it was widely used as an adjunct to transfusion therapy due to limitations in the availability of blood and logistical disturbances. Thus, it has become clear that hydroxyurea could play a remarkable role in reducing transfusion requirements of patients with haemoglobinopathies, especially when donor blood is a limited resource. CONCLUSION: Hydroxyurea is a well-tolerated oral drug which has been in use for many decades. Through its actions of reversible inhibition of ribonucleoside diphosphate reductase enzyme and fetal haemoglobin induction, it exerts many favourable effects on patients with β-haemoglobinopathies. It is currently approved for the treatment of sickle cell disease and non-transfusion dependent β-thalassaemia. Also, there are various observations to suggest that hydroxyurea is an important adjunct in the treatment of transfusion dependent β-thalassaemia which should be confirmed by randomised clinical trials. KEYWORDS: Blood transfusion; COVID-19; Haemoglobinopathies; Hydroxyurea; Ribonucleoside diphosphate reductase; Sickle cell disease; Thalassaemia; γ-Globin induction.
Correlation of genotype with phenotype in beta thalassaemia intermedia in Sri lanka
(Thalassaemia International Federation, 2015) Perera, P.S.; Silva, D.P.S.I.; Hapugoda, M.; Wickramarathne, M.N.; Wijesiriwardena, I.; Efremov, D.G.; Fisher, C.A.; Weatherall, D.J.; Premawardhena, A.
Abstract Available
A Cost-of-illness analysis of β-Thalassaemia major in children in Sri Lanka - experience from a tertiary level teaching hospital.
(BioMed Central., 2020) Reed-Embleton, H.; Arambepola, S.; Dixon, S.; Maldonado, B. N.; Premawardhena, A.; Arambepola, M.; Khan, J. A. M.; Allen, S.
BACKGROUND: Sri Lanka has a high prevalence of β-thalassaemia major. Clinical management is complex and long-term and includes regular blood transfusion and iron chelation therapy. The economic burden of β-thalassaemia for the Sri Lankan healthcare system and households is currently unknown. METHODS: A prevalence-based, cost-of-illness study was conducted on the Thalassaemia Unit, Department of Paediatrics, Kandy Teaching Hospital, Sri Lanka. Data were collected from clinical records, consultations with the head of the blood bank and a consultant paediatrician directly involved with the care of patients, alongside structured interviews with families to gather data on the personal costs incurred such as those for travel. RESULTS: Thirty-four children aged 2-17 years with transfusion dependent thalassaemia major and their parent/guardian were included in the study. The total average cost per patient year to the hospital was $US 2601 of which $US 2092 were direct costs and $US 509 were overhead costs. Mean household expenditure was $US 206 per year with food and transport per transfusion ($US 7.57 and $US 4.26 respectively) being the highest cost items. Nine (26.5%) families experienced catastrophic levels of healthcare expenditure (> 10% of income) in the care of their affected child. The poorest households were the most likely to experience such levels of expenditure. CONCLUSIONS: β-thalassaemia major poses a significant economic burden on health services and the families of affected children in Sri Lanka. Greater support is needed for the high proportion of families that suffer catastrophic out-of-pocket costs. KEYWORDS: Children; Cost-of-illness; Sri Lanka; Thalassaemia.
Deferoxamine, deferasirox, and deferiprone triple iron chelator combination therapy for transfusion-dependent β-thalassaemia with very high iron overload: a randomised clinical trial
(Elsevier Ltd, 2024-10) Premawardhena, A.; Wanasinghe, S.; Perera, C.; Wijethilaka, M.N.; Rajakaruna, R.H.M.G.; Samarasinghe, R.A.N.K.K.; Williams, S.; Mettananda, S.
BACKGROUND Many patients with β-thalassaemia die prematurely due to iron overload. In this study, we aim to evaluate the efficacy and safety of the triple combination of deferoxamine, deferasirox and deferiprone on iron chelation in patients with transfusion-dependent β-thalassaemia with very high iron overload.METHODS This open-label, randomised, controlled clinical trial was conducted at Colombo North Teaching Hospital, Sri Lanka. Transfusion-dependent β-thalassaemia patients with ferritin >3500 ng/mL were randomised 2:1 into intervention (deferoxamine, deferasirox and deferiprone) and control (deferoxamine and deferasirox) arms. Reduction in serum ferritin after six months was the primary outcome measure. Reduction in liver iron content, improvement in cardiac T2∗, and adverse effects were secondary outcome measures.FINDINGS Twenty-three patients (intervention-15, control-8) were recruited. 92% and 62% in the intervention and control arms showed a reduction in ferritin, respectively. The mean reduction of ferritin was significantly higher in intervention (−1094 ± 907 ng/mL) compared to control (+82 ± 1588 ng/mL) arm (p = 0.042). There was no statistically significant difference in the liver iron content in two arms. In the intervention arm, 67% improved cardiac T2∗ (mean change +6.72 ± 9.63 ms) compared to 20% in the control arm (mean change −3.00 ± 8.24 ms). Five patients discontinued deferiprone due to arthralgia, which resolved completely after stopping the drug.INTERPRETATION Triple combination therapy with deferoxamine, deferasirox and deferiprone is more efficacious in reducing iron burden measured by serum ferritin and showed a positive trend in reducing myocardial iron content in patients with transfusion-dependent β-thalassaemia with very high iron overload. Deferiprone has the disturbing side effect of reversible but severe arthropathy.
A Descriptive study of deep vein thrombosis (DVT) in a tertiary care hospital
(Sri Lanka Medical Association, 2008) Botheju, W.I.K.; Navaratne, A.C.R.; Somarathne, C.K.; Balasooriya, B.L.P.P.; Wijebandara, R.J.K.S.; Mandawala, M.B.S.N.; Ruwanpathirana, T.; Kasturiratne, K.T.A.A.; Hewawitharana, C.P.; Rathnasena, B.G.N.; Fernando, P.; Wijesinghe, P.S.; Premawardhena, A.
OBJECTIVE: The incidence and risk factors for DVT are not well established for the Sri Lankan population. Though believed to be an effective screening tool for DVT, the Well's Clinical score is not widely used in Sri Lankan hospitals. DESIGN, SETTING AND METHODS: Over a period of 8 months, a total of 23274 patients who presented to four units (including one general medical, one general surgical, one Gynaecology & Obstetrics, and the Orthopedic ward) of the North Colombo (Teaching) Hospital were screened for asymmetrical limb swelling more than 2 cm. The latter group were subjected to risk assessment for DVT, Well's scoring and CDU (Colour Duplex Ultrasound). RESULTS: Of the 23274 patients, 93 (0.4%) had unilateral limb swelling of which 12 (12.9%) were CDU confirmed to have DVT (0.5 per 1000). Limb swelling for more man two weeks was significantly commoner among DVT patients when compared to those without DVT (75% Vs 25.9%: p=0.001). None of the patients had been evaluated with the Well's score as a guide to refer for CDU by the relevant clinical teams. In 55 (59.1%) subjects, Well's score was 0 or less (minimum probability of DVT) and there were no subjects with DVT in this group. All 12 patients with DVT had a moderate or high probability Wells score. CONCLUSIONS: Overall incidence of DVT in the study population was lower than in other comparable published studies from Asia. Well's score which was underused by the clinicians is a highly sensitive screening tool for DVT.