Rehman Khalid, Lötsch Felix, Kremsner Peter G, Ramharter Michael
Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria; Centre de Recherches Médicales de Lambaréné, Hôpital Albert Schweitzer, Lambaréné, Gabon.
Int J Infect Dis. 2014 Dec;29:268-73. doi: 10.1016/j.ijid.2014.09.007. Epub 2014 Nov 1.
Artemisinin derivatives are the mainstay of antimalarial treatment, both for uncomplicated malaria and for severe disease. Artemisinins are known for their rapid onset of action, good tolerability, and safety. However, besides the sporadic but worrying reports of delayed parasite clearance after treatment with artemisinins, there have been an increasing number of reports of acute haemolytic anaemia following their use and the safety of this class of antimalarials is being questioned.
In this systematic review, all reports of patients experiencing haemolysis following the use of artemisinins for the treatment of malaria were identified and collated into an electronic database. Summary statistics were calculated to characterize the epidemiology and clinical features of this safety concern related to artemisinin derivatives.
A total of 37 patients were identified suffering from haemolysis following the treatment of severe malaria with artemisinin derivatives. Thirty-one cases had received intravenous artesunate, while the remaining cases were attributed to other parenteral or oral regimens of artemisinin derivatives. The majority of patients were returning travellers (n=30), and six clinical cases had been reported in paediatric patients. The median onset of haemolysis was 15 (interquartile range (IQR) 13-15) days after the initiation of treatment for the 'delayed-onset' pattern and 17 (IQR 13-22) days for the 'persistent' haemolysis pattern. The median reduction in haemoglobin due to haemolysis was 6 g/dl (IQR 4-8 g/dl). The estimated proportion of patients suffering from severe malaria experiencing haemolysis after treatment with artemisinin derivatives was 13% (95% confidence interval 9-18%), and 73% of these (i.e., 9% of the total population) required blood transfusions. No fatal outcome has been reported in the literature to date.
Haemolysis is commonly associated with the class of artemisinin drugs when used for the treatment of severe malaria. Potential causes of this safety issue are discussed. Although no deaths attributed to haemolysis have been reported so far, this safety issue may lead to life-threatening anaemia and is particularly worrying for regions where safe blood products are not readily available.
青蒿素衍生物是抗疟治疗的主要药物，无论是用于治疗非重症疟疾还是重症疟疾。青蒿素以起效迅速、耐受性良好和安全性高而闻名。然而，除了偶发但令人担忧的关于青蒿素治疗后寄生虫清除延迟的报告外，使用青蒿素后急性溶血性贫血的报告也越来越多，这类抗疟药的安全性受到质疑。
在本系统评价中，识别了所有使用青蒿素治疗疟疾后发生溶血的患者报告，并整理到一个电子数据库中。计算汇总统计数据，以描述与青蒿素衍生物相关的这一安全问题的流行病学和临床特征。
共识别出37例使用青蒿素衍生物治疗重症疟疾后发生溶血的患者。31例接受了静脉注射青蒿琥酯，其余病例归因于其他青蒿素衍生物的肠外或口服给药方案。大多数患者是归国旅行者（n = 30），儿科患者中有6例临床病例报告。溶血的中位发病时间在“延迟发作”模式下为治疗开始后15天（四分位间距（IQR）13 - 15天），“持续性”溶血模式下为17天（IQR 13 - 22天）。溶血导致的血红蛋白中位数下降为6 g/dl（IQR 4 - 8 g/dl）。估计使用青蒿素衍生物治疗重症疟疾后发生溶血的患者比例为13%（95%置信区间9 - 18%），其中73%（即占总人口的9%）需要输血。迄今为止，文献中尚未报告有致命结局。
青蒿素类药物用于治疗重症疟疾时通常与溶血有关。讨论了这一安全问题的潜在原因。尽管目前尚未报告有因溶血导致的死亡，但这一安全问题可能导致危及生命的贫血，对于难以获得安全血液制品的地区尤其令人担忧。
