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

Anuja P. Premawardhena, Dileepa Senajith Ediriweera, Amir Sabouhanian, Angela Allen, David Rees, Shanthimala de Silva, Windsor Perera, Nimal Katugaha, Mahinda Arambepola, Robert C. Yamashita, Sachith Mettananda, Nilam Jiffry, Vikita Mehta, Refai Cader, Dayananda Bandara, Timothy St Pierre, Giulia Muraca, Christopher Fisher, Abirami Kirubarajan, Shawn KhanStephen Allen, Sanath P. Lamabadusuriya, David J. Weatherall, Nancy F. Olivieri

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


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.

Original languageEnglish
Pages (from-to)e134-e141
JournalThe Lancet Global Health
Issue number1
Publication statusPublished - Jan 2022


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