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

Premawardhena, Anuja P, Ediriweera, Dileepa Senajith, Sabouhanian, Amir, Allen, Angie, Rees, David, de Silva, Shanthimala, Perera, Windsor, Katugaha, Nimal, Arambepola, Mahinda, Yamashita, Robert C, Mettananda, Sachith, Jiffry, Nilam, Mehta, Vikita, Cader, Refai, Bandara, Dayananda, St Pierre, Timothy, Muraca, Giulia, Fisher, Christopher, Kirubarajan, Abirami, Khan, Shawn, Allen, Stephen ORCID: https://orcid.org/0000-0001-6675-249X, Lamabadusuriya, Sanath P, Weatherall, David J and Olivieri, Nancy F (2022) 'Survival and complications in patients with haemoglobin E thalassaemia in Sri Lanka: a prospective, longitudinal cohort study'. Lancet Global Health, Vol 10, Issue 1, e134-e141.

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Abstract

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.

Item Type:	Article
Subjects:	WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 170 Hemolytic anemia (e.g., Sickle cell anemia) WH Hemic and Lymphatic Systems > WH 20 Research (General)
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1016/S2214-109X(21)00446-0
Depositing User:	Julie Franco
Date Deposited:	14 Dec 2021 09:38
Last Modified:	03 Feb 2022 16:43
URI:	https://archive.lstmed.ac.uk/id/eprint/19643

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