Nri-Ezedi Chisom, Ugwu Nwanneka, Ulasi Arinze, Ulasi Thomas Obiajulu
Department of Paediatrics, Nnamdi Azikiwe University, Awka, Anambra, Nigeria.
Department of Paediatrics, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra, Nigeria.
BMC Pediatr. 2025 Jul 2;25(1):487. doi: 10.1186/s12887-025-05834-y.
Sickle cell anaemia (SCA) is highly prevalent in sub-Saharan Africa and is characterized by frequent vaso-occlusive crises and other severe complications. Hydroxyurea has proven effective in reducing SCA complications by increasing foetal haemoglobin, but its use in low- and middle-income countries (LMICs) remains limited due to cost, need for regular laboratory monitoring, and concerns about safety. This study evaluates a simplified hydroxyurea dosing regimen as a practical approach to reduce emergency room visits and improve treatment adherence in paediatric SCA within a resource-limited setting.
We conducted a prospective open-label cohort study over two years (January 2022– January 2024) at a tertiary hospital in South East Nigeria. One hundred children aged 1–18 years with confirmed SCA (HbSS genotype) were started on a uniform dose of hydroxyurea (20 mg/kg/day, capped at 500 mg/day). Patients were followed monthly, and those experiencing “breakthrough vaso-occlusive crises” had their dose increased to 25 mg/kg/day (or from 500 mg to 750 mg for those at the capped dose). The primary outcome was the frequency of SCA-related emergency room visits. Secondary outcomes included treatment adherence (assessed via caregiver report of missed doses) and factors associated with adherence. Statistical analyses (t-tests, Mann–Whitney U, chi-square) were performed to compare clinical and demographic variables between adherence groups, with a significance threshold of < 0.05.
The simplified hydroxyurea regimen dramatically reduced emergency room visits. Only one patient (1% of the cohort) required an emergency visit for a vaso-occlusive crisis during the two-year period, and this patient’s dose was successfully escalated to 750 mg/day with no further crises. Overall, treatment adherence was high: 84.2% reported consistent adherence to daily hydroxyurea. Younger children demonstrated better adherence than older children (mean age of adherent patients 8.5 ± 5.3 years vs. 11.6 ± 4.2 years for non-adherent, = 0.027). Patients who were non-adherent tended to have older fathers (median paternal age 49 years vs. 44 years in adherent patients, = 0.02). Other factors—sex, socio-economic status (social class), maternal age, weight, and baseline health status—showed no significant association with adherence (all > 0.2). No severe adverse effects were observed, and the dosing approach was well-tolerated without routine laboratory monitoring.
A simplified hydroxyurea dosing strategy appears to be a safe, effective, and feasible strategy for managing paediatric SCA in a resource-limited setting. This approach resulted in a substantial reduction in vaso-occlusive crises requiring emergency care and high levels of treatment adherence. These findings suggest that simplified dosing protocols could be a valuable component of broader SCA care strategies in settings such as Nigeria. Validation through larger or comparative studies is encouraged, and we recommend that healthcare policy-makers consider piloting and supporting similar models as part of national sickle cell control efforts.
The online version contains supplementary material available at 10.1186/s12887-025-05834-y.
镰状细胞贫血（SCA）在撒哈拉以南非洲地区高度流行，其特征是频繁发生血管阻塞性危机和其他严重并发症。羟基脲已被证明可通过增加胎儿血红蛋白来有效减少SCA并发症，但由于成本、需要定期实验室监测以及对安全性的担忧，其在低收入和中等收入国家（LMICs）的使用仍然有限。本研究评估了一种简化的羟基脲给药方案，作为在资源有限的环境中减少儿科SCA患者急诊室就诊次数并提高治疗依从性的实用方法。
我们在尼日利亚东南部的一家三级医院进行了一项为期两年（2022年1月至2024年1月）的前瞻性开放标签队列研究。100名年龄在1至18岁之间确诊为SCA（HbSS基因型）的儿童开始服用统一剂量的羟基脲（20mg/kg/天，上限为500mg/天）。患者每月接受随访，那些经历“突破性血管阻塞性危机”的患者剂量增加到25mg/kg/天（对于剂量已达上限的患者，从500mg增加到750mg）。主要结局是与SCA相关的急诊室就诊频率。次要结局包括治疗依从性（通过照顾者报告的漏服剂量评估）以及与依从性相关的因素。进行统计分析（t检验、曼 - 惠特尼U检验、卡方检验）以比较依从性组之间的临床和人口统计学变量，显著性阈值为<0.05。
简化的羟基脲方案显著减少了急诊室就诊次数。在两年期间，只有一名患者（占队列的1%）因血管阻塞性危机需要急诊就诊，该患者的剂量成功增加到750mg/天，此后未再发生危机。总体而言，治疗依从性较高：84.2%的患者报告持续坚持每日服用羟基脲。年龄较小的儿童比年龄较大的儿童表现出更好的依从性（依从患者的平均年龄为8.5±5.3岁，非依从患者为11.6±4.2岁，P = 0.027）。非依从患者的父亲往往年龄较大（父亲年龄中位数，非依从患者为49岁，依从患者为44岁，P = 0.02）。其他因素——性别、社会经济地位（社会阶层）、母亲年龄、体重和基线健康状况——与依从性均无显著关联（均P>0.2）。未观察到严重不良反应，该给药方法耐受性良好，无需常规实验室监测。
简化的羟基脲给药策略似乎是在资源有限的环境中管理儿科SCA的一种安全、有效且可行的策略。这种方法使需要紧急护理的血管阻塞性危机大幅减少，并实现了高水平的治疗依从性。这些发现表明，简化给药方案可能是尼日利亚等地区更广泛的SCA护理策略的重要组成部分。鼓励通过更大规模或对比研究进行验证，我们建议医疗保健政策制定者考虑试点并支持类似模式，作为国家镰状细胞病控制工作的一部分。
在线版本包含可在10.1186/s12887 - 025 - 05834 - y获取的补充材料。
