Department of Medicine, Faculty of Medicine, University of Kelaniya, Sri Lanka.
Health Data Science Unit, Faculty of Medicine, University of Kelaniya, Sri Lanka.
Lancet Glob Health. 2022 Jan;10(1):e134-e141. doi: 10.1016/S2214-109X(21)00446-0. Epub 2021 Nov 26.
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.
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.
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.
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.
Wellcome Trust, Medical Research Council, US March of Dimes, Anthony Cerami and Ann Dunne Foundation for World Health, and Hemoglobal.
在全球范围内，血红蛋白 E β-地中海贫血是最常见的严重 β-地中海贫血基因型。由于这种地中海贫血形式缺乏长期数据，因此基于证据的管理具有挑战性。我们进行了一项长期观察性研究，以确定与血红蛋白 E 地中海贫血患者生存和并发症相关的因素。
在这项前瞻性、纵向队列研究中，我们纳入了 1997 年 1 月 1 日至 2001 年 12 月 31 日期间在斯里兰卡库鲁内加拉国家地中海贫血中心就诊的所有血红蛋白 E 地中海贫血患者。患者每年评估多达 3 次。在此期间，输血、脾切除术和螯合治疗的方法发生了变化。使用 Kaplan-Meier 生存函数估计曲线评估组间生存率，并使用 Cox 比例风险模型确定死亡率的危险因素。
共招募了 109 名患者（54 名男性[50%]；55 名女性[50%]），并进行了中位数为 18 年（IQR 14-20）的随访。招募时的中位年龄为 13 岁（范围 8-21）。32 名（29%）患者在随访期间死亡。所有患者的中位生存时间为 49 年（95%CI 45-未达到）。男性患者（危险比[HR]2.51，95%CI 1.16-5.43）、有严重感染史的患者（调整 HR 8.49，2.90-24.84）和血清铁蛋白浓度估计的体铁负荷较高的患者（调整 HR 1.03，1.01-1.06/每 100 个单位）的中位生存时间更差。脾切除术虽然与死亡或严重感染风险的统计学显著增加无关，但最终并未消除 73 名患者中 42 名（58%）患者对定期输血的需求。血红蛋白浓度等于或小于 4.5 g/dL（vs 浓度大于 4.5 g/dL）、血清铁蛋白浓度大于 1300μg/L（vs 浓度等于或小于 1300μg/L）和肝铁浓度大于 5mg/g 干重的肝脏（vs 浓度等于或小于 5mg/g）与较差的生存相关。
与高资源国家的重型地中海贫血和不涉及血红蛋白 E 等位基因的中间型地中海贫血相比，血红蛋白 E 地中海贫血患者常发生并发症和缩短的生存时间。该疾病的管理方法仍不确定，应进行前瞻性研究，以评估改善体铁控制的改变输血方案是否可以提高生存率。
惠康信托基金会、医学研究理事会、美国生育基金会、安东尼·塞拉米和安·邓恩基金会世界卫生组织以及 Hemoglobal。
