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

BACKGROUND Worldwide, haemoglobin E β-thalassaemia is the most common genotype of severe β-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

Spontaneous intracranial haemorrhage in haemophilia A

Spontaneous intracranial haemorrhage is rarely seen with clotting disorders. Haemophilia A, an X linked recessive clotting disorder, usually presents with haemarthrosis or prolonged bleeding from cut injuries

Picture Story An unusual presentation of Beckwith Wiedemann Syndrome

This baby was born at term by normal vaginal delivery and weighed 4.14 kg. Antenatal period had been uneventful with regular clinic follow up. He was found to have macrosomia, macroglossia, omphalocele (Figure 1) and linear fissures in ear lobules (Figure 2). He developed episodes of hypoglycaemia on the first day of life. A diagnosis of Beckwith Wiedemann syndrome was made and surgical repair of the omphalocele was done on the 2nd day of life. exploratory laparotomy was done on the 9th day of life and the malrotation corrected. He was then transferred to a medical ward for management of persistent hypoglycaemia. He later developed pyogenic meningitis and succumbed on the 18th day of life. Figure 1. Macrosomia & macroglossia Figure 3. Barium meal showing duodenojejunal flexure and small intestinal bowel loops on right side of abdomen Beckwith Wiedemann syndrome is usually sporadic. The gene for the syndrome is located at 11 p 15.5. The characteristic phenotype occurs as a result of a variety of different genetic mechanisms all of which result in an imbalance of the gene. Currently, it appears that maternal copy of the gene is normally imprinted or inactivated. Figure 2. Linear fissures in ear lobule Two days later he developed bilious vomiting with abdominal distension. A barium meal showed the duodenojejunal flexure displaced to the right with small intestinal bowel loops on the right side of the vertebral column (Figure 3). These findings were compatible with intestinal malrotation. A

Distal aphalangia, microcephaly and mental retardation

generalised convulsions. He was the third child born to consanguineous parents. The antenatal and perinatal period of this child had been normal. At 3 months of age he developed generalised convulsions and was treated with phenobarbitone at the Nawalapitiya Base Hospital. However, subtle seizures persisted at a frequency of about 1 or 2 seizures a month. At about 15 months of age the seizure frequency increased. He also had global development delay. On examination he had dysmorphic features. The occipito-frontal circumference was 46 cm (<3rd centile, [1], length of child 89 cm (< 3rd centile) and weight 13.5 kg (between 10th and 25th centile). The dysmorphic features were mainly confined to hands and feet. The distal phalanges of all the four finger

A case of hereditary persistence of fetal haemoglobin

(Key words: hereditary persistence of fetal haemoglobin, HPFH

Original Articles Evaluation of prescription compliance and medication accuracy in a paediatric unit at the Lady Ridgeway Hospital, Colombo

Objectives To assess variation between prescription intentions and what was actually administered to paediatric patients and the problem of converting adult dosages to paediatric doses in a ward setting. Method A prospective descriptive study was carried out at Ward 01, Lady Ridgeway Hospital, Colombo. Administration of drugs to 170 patients was directly observed and recorded during drug rounds. Converted adult dosages for paediatric administration were analyzed to determine the content of active ingredient per unit dose prepared. Results In 170 patients observed, correct drugs were administered in every instance except one. At all times drugs were administered via intended route and the timing of drug rounds was capable of accommodating the prescribed dosing frequencies. However in 17.64% anomalies between prescribed dose and administered dose were encountered for both orally and intravenously administered drugs

admitted to the Professorial Paediatric Unit at Lady

Objective To study in detail deaths of patient

Year Vaccine Researcher/Developer

In the field of vaccine development Jenner and Pasteur easily stand out as the true pioneers. Although Edward Jenner first attempted systematic immunisation against smallpox in 1796, an entire century actually went by before Louis Pasteur in 1885 administered post exposure rabies vaccine cultured in rabbit spinal cord to a young man severely bitten by a dog. Since then during the last century many other vaccines were developed b