Wang Winfred C
St Jude Children's Research Hospital, Department of Hematology, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA.
Expert Opin Pharmacother. 2008 Dec;9(17):3069-82. doi: 10.1517/14656560802519878.
Sickle cell disease (SCD) is characterized by acute and chronic complications, which can affect almost any organ system in the body. Recently, there has been remarkable progress in the pharmacotherapy of SCD, and therapeutic options have been greatly expanded beyond red blood cell transfusion and hematopoietic stem cell transplantation. The most successful approach has been the stimulation of Hb F production through drugs such as hydroxycarbamide, which reduces the frequency of vaso-occlusive pain events and is the only therapeutic agent at present approved by the US Food and Drug Administration for SCD. Hydroxycarbamide is still greatly underused, but its indications are being broadened through a number of Phase II and III clinical trials. Other Hb F-promoting agents such as decitabine and butyrate have been studied less extensively. Another approach is the use of agents that reduce red cell dehydration through blockage of ion channels in the red cell membrane. Also under investigation is manipulation of nitric oxide (NO) metabolism to counteract the effects of chronic hemolysis. As yet, unproven drugs include agents that target coagulation, inflammation and adhesion to vascular endothelium. In the near future we expect to see exploration of the efficacy of drug combinations and an expansion in the use of the proven therapeutic, hydroxycarbamide.
镰状细胞病（SCD）的特点是存在急性和慢性并发症，几乎可影响身体的任何器官系统。近年来，SCD的药物治疗取得了显著进展，治疗选择已大大扩展，不再局限于红细胞输血和造血干细胞移植。最成功的方法是通过羟基脲等药物刺激胎儿血红蛋白（Hb F）的产生，这减少了血管闭塞性疼痛事件的发生频率，且是目前美国食品药品监督管理局批准用于SCD的唯一治疗药物。羟基脲的使用仍严重不足，但通过多项II期和III期临床试验，其适应证正在扩大。其他促进Hb F生成的药物，如地西他滨和丁酸盐，研究相对较少。另一种方法是使用通过阻断红细胞膜离子通道来减少红细胞脱水的药物。此外，正在研究通过调节一氧化氮（NO）代谢来对抗慢性溶血的影响。目前未经证实的药物包括针对凝血、炎症和与血管内皮粘附的药物。在不久的将来，我们有望看到对药物联合疗效的探索以及已证实的治疗药物羟基脲使用的扩大。
