Merrem's Hump-Nosed Viper (Hypnale hypnale) Bite on the Tongue of an Infant Leading to Upper Airway Obstruction: An Unusual Presentation.

Snakebites in unusual anatomical locations may lead to life-threatening consequences. Merrem's hump-nosed viper (Hypnale hypnale) is a medically important snake in Sri Lanka and India that causes many bites and envenomings. Their bites occur almost exclusively on upper and lower limbs and commonly result in local effects, with some patients developing systemic envenoming. No antivenom is available for treating envenoming by H. hypnale. We report an unusual case of H. hypnale bite on the tongue of a 10-month-old infant resulting in rapid local swelling of the tongue and floor of the mouth, requiring prompt intervention to prevent life-threatening upper airway obstruction. Early tracheostomy prevented upper airway obstruction and, along with supportive steroid therapy and antibiotics, led to a complete resolution of the local effects of the infant without permanent disability, despite the unavailability of antivenom.

Leg Ulcers: A Report in Patients with Hemoglobin E Beta Thalassemia and Review of the Literature in Severe Beta Thalassemia.

BACKGROUND: Leg ulcers are a frequent complication in patients with the inherited hemoglobin disorders. In thalassemia, the literature is limited, and factors associated with the development of leg ulcers in hemoglobin E (HbE) beta thalassemia, the most common form of severe beta-thalassemia worldwide, have not previously been reported. METHODS: We reviewed all available medical records of patients with HbE beta thalassemia to document the onset of leg ulcers at the 2 largest treatment centers in Sri Lanka. We reviewed the literature to identify studies reporting outcomes of interventions for ulcers in severe thalassemia. RESULTS: Of a total of 255 actively registered patients with HbE thalassemia in the 2 centers, 196 patient charts were evaluable. A leg ulcer with a documented date of onset was recorded in 45 (22%) of 196 evaluable patients, aged (mean ± SEM) 22.2 ± 1.4 years. Most had been irregularly transfused; steady-state hemoglobin was 6.4 ± 0.2 g/dL. Treatment achieving healing in 17 patients included transfusions, antibiotics, oral zinc, wound toileting, and skin grafting. CONCLUSION: Leg ulcers may be more common in HbE beta thalassemia than in other forms of thalassemia. A systematic approach to treatment will be needed to document the prevalence and factors placing such patients at risk for leg ulcers. Controlled trials to evaluate the optimal treatment of this common complication are indicated.

Blood transfusion therapy for ß-thalassemia major and hemoglobin E ß-thalassemia: Adequacy, trends, and determinants in Sri Lanka.

BACKGROUND: Regular blood transfusion therapy still remains the cornerstone in the management of ß-thalassemia. Although recommendations are clear for patients with ß-thalassemia major, uniform transfusion guidelines are lacking for patients with hemoglobin E ß-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 ß-thalassemia major and hemoglobin E ß-thalassemia. METHODS/PROCEDURE: This cross-sectional study was performed among all regularly transfused patents with ß-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 ß-thalassemia major, whereas 16% had hemoglobin E ß-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 ß-thalassemia compared with ß-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 ß-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 ß-thalassemia have low pretransfusion hemoglobin levels despite receiving large transfusion volumes. Patients with hemoglobin E ß-thalassemia are undertransfused and specific recommendations should be developed to guide transfusions in these patients.

Health related quality of life among children with transfusion dependent ß-thalassaemia major and haemoglobin E ß-thalassaemia in Sri Lanka: a case control study.

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 ß-thalassaemia major and haemoglobin E ß-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 ß-thalassaemia (ß-thalassaemia major and haemoglobin E ß-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 ß-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 ß-thalassaemia major and 43 (16%) had haemoglobin E ß-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 ß-thalassaemia compared to ß-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 ß-thalassaemia still remains low. This is more pronounced in the subset of patients with haemoglobin E ß-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 ß-thalassaemia.

Methemoglobinemia and ascorbate deficiency in hemoglobin E ß thalassemia: metabolic and clinical implications.

During investigations of the phenotypic diversity of hemoglobin (Hb) E ß thalassemia, a patient was encountered with persistently high levels of methemoglobin associated with a left-shift in the oxygen dissociation curve, profound ascorbate deficiency, and clinical features of scurvy; these abnormalities were corrected by treatment with vitamin C. Studies of erythropoietin production before and after treatment suggested that, as in an ascorbate-deficient murine model, the human hypoxia induction factor pathway is not totally dependent on ascorbate levels. A follow-up study of 45 patients with HbE ß thalassemia showed that methemoglobin levels were significantly increased and that there was also a significant reduction in plasma ascorbate levels. Haptoglobin levels were significantly reduced, and the high frequency of the 2.2 haptoglobin genotype may place an additional pressure on ascorbate as a free-radical scavenger in this population. There was, in addition, a highly significant correlation between methemoglobin levels, splenectomy, and factors that modify the degree of globin-chain imbalance. Because methemoglobin levels are modified by several mechanisms and may play a role in both adaptation to anemia and vascular damage, there is a strong case for its further study in other forms of thalassemia and sickle-cell anemia, particularly when splenic function is defective.

Alpha thalassaemia and extended alpha globin genes in Sri Lanka.

The α-globin genes were studied in nine families with unexplained hypochromic anaemia and in 167 patients with HbE ß 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 ß 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 ß thalassaemia. As well as emphasising the ameliorating effect of α thalassaemia on HbE ß 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.

Survival and complications in patients with haemoglobin E thalassaemia in Sri Lanka: a prospective, longitudinal cohort study.

BACKGROUND: Worldwide, haemoglobin E ß-thalassaemia is the most common genotype of severe ß-thalassaemia. The paucity of long-term data for this form of thalassaemia makes evidence-based management challenging. We did a long-term observational study to define factors associated with survival and complications in patients with haemoglobin E thalassaemia. METHODS: In this prospective, longitudinal cohort study, we included all patients with haemoglobin E thalassaemia who attended the National Thalassaemia Centre in Kurunegala, Sri Lanka, between Jan 1, 1997, and Dec 31, 2001. Patients were assessed up to three times a year. Approaches to blood transfusions, splenectomy, and chelation therapy shifted during this period. Survival rates between groups were evaluated using Kaplan-Meier survival function estimate curves and Cox proportional hazards models were used to identify risk factors for mortality. FINDINGS: 109 patients (54 [50%] male; 55 [50%] female) were recruited and followed up for a median of 18 years (IQR 14-20). Median age at recruitment was 13 years (range 8-21). 32 (29%) patients died during follow-up. Median survival in all patients was 49 years (95% CI 45-not reached). Median survival was worse among male patients (hazard ratio [HR] 2·51, 95% CI 1·16-5·43), patients with a history of serious infections (adjusted HR 8·49, 2·90-24·84), and those with higher estimated body iron burdens as estimated by serum ferritin concentration (adjusted HR 1·03, 1·01-1·06 per 100 units). Splenectomy, while not associated with statistically significant increases in the risks of death or serious infections, ultimately did not eliminate a requirement for scheduled transfusions in 42 (58%) of 73 patients. Haemoglobin concentration less than or equal to 4·5 g/dL (vs concentration >4·5 g/dL), serum ferritin concentration more than 1300 µg/L (vs concentration ≤1300 µg/L), and liver iron concentration more than 5 mg/g dry weight of liver (vs concentration ≤5 mg/g) were associated with poorer survival. INTERPRETATION: Patients with haemoglobin E thalassaemia often had complications and shortened survival compared with that reported in high-resource countries for thalassaemia major and for thalassaemia intermedia not involving an allele for haemoglobin E. Approaches to management in this disorder remain uncertain and prospective studies should evaluate if altered transfusion regimens, with improved control of body iron, can improve survival. FUNDING: Wellcome Trust, Medical Research Council, US March of Dimes, Anthony Cerami and Ann Dunne Foundation for World Health, and Hemoglobal.

Psychological morbidity among children with transfusion dependent ß-thalassaemia and their parents in Sri Lanka.

BACKGROUND: Thalassaemia is a chronic disease which requires lifelong treatment in a majority. Despite recent advances in the medical care, minimal attempts are made to improve psychological health in these patients. In this study, we aim to describe the psychological morbidity in patients with transfusion dependent ß-thalassaemia and their mothers in Sri Lanka. METHODS: This case control study was conducted in the three largest thalassaemia centres of Sri Lanka. All patients with transfusion dependent ß-thalassaemia aged 4-18 years were recruited as cases whilst a randomly selected group of children without chronic diseases were recruited as controls. Psychological morbidity of children was assessed using the Strengths and Difficulties Questionnaire and depressive symptoms of mothers was assessed by the Centre for Epidemiological Studies Depression Scale. RESULTS: 288 transfusion dependent ß-thalassaemia patients and equal number of controls were recruited. Abnormal emotional, conduct, hyperactivity and peer relationship symptom scores were reported by 18%, 17%, 9% and 14% of patients with thalassaemia respectively. Prevalences of abnormal psychological symptom scores in all domains were significantly higher among patients compared to controls. Abnormal conduct symptoms were significantly more prevalent among patients with HbE ß-thalassaemia and those with suboptimal pretransfusion haemoglobin levels, lower transfusion volumes, hypothyroidism and undernutrition. Short stature was associated with abnormal emotional and hyperactivity scores. Depressive symptoms were significantly higher among mothers of patients with thalassaemia. Higher depressive symptom scores in mothers were significantly associated with abnormal emotional, conduct and peer relationship symptom scores in children. CONCLUSIONS: A higher proportion of patients with transfusion dependent ß-thalassaemia had abnormal psychological symptom scores. Abnormal conduct symptoms were more prevalent among patients with HbE ß-thalassaemia, those who were inadequately transfused and having hypothyroidism and undernutrition. Mothers of the children with transfusion dependent ß-thalassaemia had significantly higher depressive symptoms which were significantly associated with psychological symptoms among children.

Sickle cell disease in Sri Lanka: clinical and molecular basis and the unanswered questions about disease severity.

BACKGROUND: Though case reports and limited case series of Sickle cell disease in Sri Lanka have been reported previously, no attempt has been made hitherto to undertake a comprehensive genotypic-phenotypic analysis of this "rare" group of patients. RESULTS: All accessible Sickle cell disease patients, totaling 60, including, 51 Sickle ß-thalassaemia and 9 homozygous sickle patients were enrolled from seven thalassaemia treatment centres between December 2016-March 2019. The majority of patients were of Sinhalese ethnicity (n = 52, 86.67%). Geographically, two prominent clusters were identified and the distribution of Sickle haemoglobin in the island contrasted markedly with the other haemoglobinopathies. 3/ 9 homozygous sickle patients and 3/ 51 Sickle ß-thalassaemia patients were receiving regular transfusion. Joint pain was the commonest clinical symptom among all sickle cell disease patients (n = 39, 65.0%). Dactylitis was significantly more common in homozygous sickle patients compared with the Sickle ß-thalassaemia groups (p 0.027). Two genetic backgrounds sickle mutation were identified namely, Arab Indian and Benin. Among the regulators of Foetal hemoglobin in Sickle patients of the present study rs1427407 G > T seemed to be the most prominent modifier, with a significant association with Foetal haemoglobin levels (p 0.04). CONCLUSIONS: Overall, the clinical course of the Asian version of Sickle cell disease in Sri Lanka appears to be milder than that described in India.

Sociodemographic profile and oral health status of thalassemic patients attending the National Thalassaemia Centre, Kurunegala, Sri Lanka.

AIM: The aim of the present study was to investigate the sociodemographic profile and oral health status (Decayed, Missing, Filled Teeth [DMFT] and periodontal health) of thalassemic patients compared to healthy individuals. METHODS: The data were collected by means of an interviewer-administered, pretested, and validated questionnaire, followed by oral examination. Patients attending the outpatient department, who were age and sex matched, but without any diagnosed or suspected long-term illnesses, were considered for the control group. Both groups were compared in terms of facial profile, skeletal pattern, facial angles, DMFT, and periodontal health (plaque index, bleeding on probing, and probing pocket depth). RESULTS: The association of convex facial profile and class II skeletal pattern with Thalassemic status was statistically significant when compared to healthy individuals. Decayed, missing, and filled teeth in the permanent and deciduous dentition, plaque index, and probing pocket depths of the control group were significantly higher compared with the thalassemic group. Surprisingly, 67.8% of thalassemic patients did not show bleeding on probing. CONCLUSION: Families of the thalassemic patients attending the National Thalassaemia Centre are from a low socioeconomic background. Their DMFT and periodontal health are significantly better than those of healthy individuals.