Browsing by Author "Silva, D.P.S.I."

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Chracterisation of beta giobin mutations in Sri Lankan patients with betathalassaemia intermedia
(Sri Lanka Medical Association, 2013) Perera, S.; Silva, D.P.S.I.; Hapugoda, M.; Wickramarathne, M.N.; Wijesirwardhena, I.; Efremove, D.G.; Fisher, C.A.; Weatherall, D.J.; Premawardhena, A.P.
INTRODUCTION AND OBJECTIVES: Patients with beta thalassaemia intermedia account for a third of patients attending thalassaemia clinics in Sri Lanka. They show immense phenotypic diversity, the genetic basis for which has not been identified so far. Objective were to characterise beta globin gene mutations in Sri Lankan thalassaemia intermedia patients and to determine how it to influences disease severity. METHODS: We identified 64 thalassaemia intermedia patients from the five main thalassaemia centers; Anuradhapura (n= 6), Kuruncgala (n= 4), Ragama (n= 42), Badulla (n=7) and Chilaw (n=5). Their beta globin DNA sequences were analyzed using ABI PRISM 313lx genetic analyser. RESULTS: Of sixteen patients identified to be homozygous for beta mutations, eleven carried mild beta alleles, IVSI 5 G_C (n= 10) and a rare homozygous promoter mutation - 90 C_T (N=l). Other five were shown to have different types of severe iputations in homozygous state. Nearly half the sample (n=39) was heterozygous for beta mutations. Of them 33 showed mild to severe mutation in one of the alleles IVSI-5 G_C (n=12), IVSI-1 G_A (n= 11) were the commonest. Two patients who were hetcrozygones for beta mutation had a highly unstable Hb variant haemoglobin Mizuho causing severe haemolytic anacma. Hb variants Hb G-Szuhu and Hb G-Coushatta were identified in two patients. CONCLUSIONS: We identified types of beta mutations in some patients with thalassaemia intermedia, which account for the clinical severity.
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.
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
Do thalassaemic patients, their parents and caregivers support termination of pregnancy as a method for thalassaemia prevention?
(Sri Lanka Medical Association, 2011) Nandasiri, A.S.D.; Dissakaruna, A.M.D.D.; Silva, D.P.S.I.; Nishad, A.A.N.; Premawardhena, A.P.
INTRODUCTION AND OBJECTIVES: The only proven way to prevent thalassaemia, the commonest monogenic disease in Sri Lanka, is premarital and ante natal counselling followed by pre-natal diagnosis (PND) and termination of affected fetuses. Termination of pregnancy (TOP) of a thalassaemic fetus is illegal in Sri Lanka. This study assesses the attitudes towards termination of thalassaemic fetuses among the patients themselves, their immediate family members and hospital staff. METHODS: A single operator administered a pre-formed questionnaire to test the knowledge and attitudes towards TOP among patients, parents, immediate family members and hospital staff associated with the thalassaemia unit; over a two month period from Is' of March 2010, at the Thalassaemia Unit, NCTH, Ragama. RESULTS: A total of 24 adult patients with thalassaemia major (TM) and 15 with thalassaemia intermedia (TIM) 39 parents and 25 hospital staff were interviewed. 39.1% of TMs, 60% TIMs, 60% hospital staff, 54.5% parents were aware of PND. 78.8% of TMs, 87% TIMs, 60% hospital staff, 85.3% parents knew that abortion of a thalassaemic fetus was illegal. Only 39.1% of TM supported TOP, if thalassaemia was diagnosed antenatally whilst 73.3% TIMs, 80% hospital staff and 88.57% parents were supportive (pO.OQl). 78.2% of TMs, 100% in all other groups support premarital screening and making partner screening compulsory. CONCLUSIONS: Though there is strong support for TOP from parents and hospital staff, this is not so with patients with TM. However partner selection prior to marriage seems to have more uniform support.
An islandwide hospital based epidemiological survey of haemoglobinopathies and an assessment of standards of care in 23 centres
(Sri Lanka Medical Association, 2017) Premawardhena, A.P.; Mudiyanse, R.M.; Jifri, M.N.; Nelumdeniya, U.B.P.; Silva, D.P.S.I.; Nizri, A.H.M.; Rajiyah, M.O.F.; de Silva, T.U.N.; Pushpakumara, K.R.C.; Dissanayake, D.M.R.; Jansz, M.; Rifaya, M.I.; Navarathne, N.M.U.S.B.; Arambepola, W.W.M.M.; Thirukumaran, V.; Mendis, D.; Weerasekara, K.P.; de Silva, N.N.; Vaidyanatha, U.S.de.S.; Mettananda, D.S.G.; Oliveri, N.F.; Weatherall, D.J.
INTRODUCTION & OBJECTIVES: There is no database for haemoglobinopathy patients in Sri Lanka resulting in imprecise knowledge about the distribution and standards of care among patients managed in different centres in the island. The prevention programme commenced in 2007 is not centrally monitored. METHODS: We carried out centre-wise visitation and data gathering of patients with haemoglobinopathies in 2015. 23 centres were visited by researchers who gathered information from patient records. RESULTS: Data was obtained of 1768 patients. Three centres had over 200 patients each and another three centres had between 50-100 patients. There were 8 centres with less than 10 patients each. Beta thalassaemia major (BTM) accounted for 1207 (68.26%) patients. There were 363 patients (20.53%) with Haemoglobin E-β thalassaemia. Sickle cell-β thalassaemia accounted for 51 patients (2.88%). The mean age of BTM patients was 13 years (range 2-44). Ethnic distribution of the haemoglobinopathies (82.5% Sinhalese, 12% Muslims and 5.2% in Tamils) was discrepant to the national ethnic data. Islandwide mean number of new births of all thalassaemics recorded showed a reduction from 66/year between 2004 - 2009 to 48/year between 2010 to 2015.Clinical record keeping was not systematic in most units thus complication rates were hard to obtain. Death data were available only in two units. CONCLUSION: This study identified significant inconsistencies in haemoglobinopathy care between centres. Existence of small centres needs to be recognized by the Ministry of Health. A reducing trend of new births over the last decade was observed.
Pulmonary arterial hypertension in thalassaemia patients- does splenectomy and disease severity increase the risk?
(Sri Lanka Medical Association, 2011) Premawardana, N.P.; Nandasiri, A.S.D.; Ranaweera, A.G.R.M.A.; Nishad, A.A.N.; Silva, D.P.S.I.; Premawardhena, A.P.
INTRODUCTION AND OBJECTIVES: Pulmonary arterial hypertension (PAH) has been described in patients with thalassaemia. A causative association with splenectomy has been postulated. Our previous observations differed from this. We aimed to study these factors in our patients. METHODS: Pulmonary artery pressure (PAP) and other data of thaiassaemics attending the Thalassaemia Unit, Ragarna were studied using clinic records. PAP was measured using trans-thoracic 2D echocardiography. Four categories were separately analysed: thalassaemia major (TM) with splenectomy (A) and without (B), thalassaemia intermedia (TI) with splenectomy (C) and without (D). PAH was defined as PAP over 25 mm Hg. RESULTS: A total of 74 patients were studied, 60 (81%) with TM and 14 (19%) with TI. 25 of TMs (41%) and 10 of TIs (71%) had splenectomy (p <0.05). Mean ages (SD) of TM and TI were 20.71(8.4) and 32.6 (13.3) years respectively. Those of categories ABCD were 20.9 (7.4), 20.7 (9.1), 27 (9.6) and 46 (12.3) years. A total of 16 (21.6%) of all patients had PAH (95% CI13.8-32.3). This included 13 (21.7%) TM patients and three (21.4%) with TI (p-0.98). The prevalence of PAH was 17.1% (95 CI 8.4-33.5) in splenectomised thalassaemia patients and 25.6% (95% CI 16.5-43.8) in non splenectomised patients (p= 0.37), and in categories A,B,C,D were 16%, 23%, 20% and 25% respectively. Mean of PAP of splenectomised with PAH is 39 mmHg (SD=4.5) and in non splenectomised with PAH was 34.9 mmHg (SD=5.3) (p=0.8). CONCLUSIONS: PAH is a significant complication in patients with thalassaemia. However the severity of disease nor the splenectomy status were found to be causatively linked in our study.