Headache: an important symptom possibly linked to white matter lesions in thalassaemia.

Neurological manifestations are reported only occasionally in patients with thalassaemia and are given much less prominence than the complications related to anaemia and iron overload. White matter changes (WMCs) on magnetic resonance imaging (MRI) in patients with thalassaemia were first reported two decades ago but the significance of these lesions remains unclear. We studied the neurological and cognitive manifestations in 82 older patients with thalssaemia [25 Thalassaemia major (TM), 24 thalassaemia intermedia (TI) and 33 haemaglobin E ß thalassaemia (EBT)] and 80 controls, and found that headaches were more common in thalassaemia patients (50/82, 61%) than in controls (18/80, 22·5%: P < 0·001). WMCs on MRI were found in 20/82 (24·3%) patients and 2/29 (6·9%) controls had (P = 0·078). WMC were more common among those with headaches (17/50: 34%) than in those without headache (3/32; 9·3%) (P = 0·023). WMCs were not associated with reduction of cognition. Nevertheless, cognition was lower in the TI and EBT groups compared with those with TM (P = 0·002). The association of headache with WMC in thalassaemia has not been reported before and warrants further study.

A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent ß-thalassaemia.

Hydroxyurea is an antimetabolite drug that induces fetal haemoglobin in sickle cell disease. However, its clinical usefulness in ß-thalassaemia is unproven. We conducted a randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of hydroxyurea in transfusion-dependent ß-thalassaemia. Sixty patients were assigned 1:1 to oral hydroxyurea 10-20 mg/kg/day or placebo for 6 months by stratified block randomisation. Hydroxyurea treatment did not alter the blood transfusion volume overall. However, a significantly higher proportion of patients on hydroxyurea showed increases in fetal haemoglobin percentage (89% vs. 59%; p < 0.05) and reductions in erythropoietic stress as measured by soluble transferrin receptor concentration (79% vs. 40%; p < 0.05). Based on fetal haemoglobin induction (> 1.5%), 44% of patients were identified as hydroxyurea-responders. Hydroxyurea-responders, required significantly lower blood volume (77 ± SD27ml/kg) compared to hydroxyurea-non-responders (108 ± SD24ml/kg; p < 0.01) and placebo-receivers (102 ± 28ml/kg; p < 0.05). Response to hydroxyurea was significantly higher in patients with HbE ß-thalassaemia genotype (50% vs. 0%; p < 0.01) and Xmn1 polymorphism of the γ-globin gene (67% vs. 27%; p < 0.05). We conclude that oral hydroxyurea increased fetal haemoglobin percentage and reduced erythropoietic stress of ineffective erythropoiesis in patients with transfusion-dependent ß-thalassaemia. Hydroxyurea reduced the transfusion burden in approximately 40% of patients. Response to hydroxyurea was higher in patients with HbE ß-thalassaemia genotype and Xmn1 polymorphism of the γ-globin gene.

A "One-Stop" Screening Protocol for Haemoglobinopathy Traits and Iron Deficiency in Sri Lanka.

Introduction: The high frequencies of carriers of severe haemoglobinopathies and of iron deficiency in Southeast Asia require reliable and affordable tests to improve on current screening procedures. Objectives: We evaluate a "one stop" approach using the THALCON dichlorophenolindophenol (DCIP) and one-tube osmotic fragility (OF) tests and measurement of Zinc Protoporphyrin (ZPP) to detect and distinguish HbE and ß-thalassaemia traits from iron deficiency. We compare findings with current screening practice in Sri Lanka that relies on the identification of low mean red cell volume and/or mean red cell hemoglobin for this purpose. Methods: Between November 2017 and May 2018, we undertook a cross-sectional survey of secondary school students in Gampaha district, Sri Lanka. The THALCON-DCIP and OF tests were compared to capillary electrophoresis (CE), used as a gold standard to detect haemoglobinopathies. ZPP was measured in whole blood. Plasma ferritin and C-reactive protein (CRP) were measured in students with a raised ZPP concentration. Results: We collected venous blood samples from 1,324/1,332 (99.4%) students. The median age of the students was 17 (IQR 16-18) years, all were Sinhalese and 814/1,324 (61.5%) were female. CE identified 3 students with HbE trait and 26 students with ß-thalassaemia trait. The THALCON-DCIP test was positive only in the 3 students with HbE (sensitivity 100%, 95% CI 29.2-100.0; specificity 100%, 95% CI 99.7-100.0). The THALCON-OF test identified all 26 students with ß-thalassaemia trait (sensitivity = 100%, 95% CI 86.8-100.0) and 287 students with a normal CE result (specificity = 77.9%; 95% CI 75.5-80.1). It was also positive in 2/3 (66.7%) students with HbE trait. Iron deficiency (ZPP > 70 µmol/mol heme) was present in 118/1,240 (9.5%) students with a normal hemoglobin genotype, all of whom had plasma ferritin <15 ng/ml and CRP <5 mg/L. Conclusion: This one-stop approach offers reliable and affordable population screening for both haemoglobinopathy traits and iron deficiency in resource-limited settings where these conditions are common and ensures that iron supplements are targeted only to those who require them. Further work is warranted to refine the OF test to reduce the number of false positive results.

A nationwide survey of hospital-based thalassemia patients and standards of care and a preliminary assessment of the national prevention program in Sri Lanka.

OBJECTIVES: Our aim was to describe the numbers and distribution of patients with different types of thalassemia and to assess the standards of care in all thalassemia treatment centers throughout Sri Lanka and the success of the ongoing prevention programme. METHODS: This cross-sectional island-wide survey was conducted by two trained medical graduates, who visited each thalassemia center to collect data from every patient, using a standardized form. Data was collected through review of patient registers and clinical records. RESULTS: We collected data on 1774 patients from 23 centers. 1219 patients (68.7%) had homozygous ß-thalassemia, 360 patients (20.3%) had hemoglobin E ß-thalassemia, and 50 patients (2%) had sickle ß-thalassemia. There were unacceptably high serum ferritin levels in almost all centers. The annual number of births of patients with ß-thalassaemia varied between 45-55, with little evidence of reduction over 19 years. CONCLUSIONS: Central coordination of the treatment and ultimately prevention of thalassemia is urgently needed in Sri Lanka. Development of expert centers with designated staff with sufficient resources will improve the quality of care and is preferred to managing patients in multiple small units.