The modern use of hydroxyurea for children with sickle cell anemia.

From initial small proof-of-principle studies to multicenter phase III controlled clinical trials and then numerous open-label studies, the consistent benefits of once-daily oral hydroxyurea have been demonstrated across the lifespan.

从最初的初步小规模概念验证研究到多中心的III期对照临床试验，再到众多的开放标签研究，每天一次口服羟基脲的一致益处已在整个生命过程中得到证明。

Elevated fetal hemoglobin (HbF) serves as the most important treatment response, as HbF delays sickle hemoglobin polymerization and reduces erythrocyte sickling.

升高的胎儿血红蛋白（HbF）作为最重要的治疗反应指标，因为HbF可以延缓镰状血红蛋白的聚合，并减少红细胞镰状化。

Increased amounts of HbF, especially when distributed across the majority of erythrocytes, improve clinical outcomes by reducing hemolytic anemia and preventing vaso-occlusion, thereby ameliorating both acute and chronic - and overt and covert - complications.

特别是当HbF分布在大多数红细胞中时，增加的HbF量通过减少溶血性贫血和预防血管阻塞，改善了临床结果，从而缓解了急性和慢性、明显和隐匿的并发症。

Additional benefits of hydroxyurea beyond HbF induction include lower neutrophil and platelet counts, reduced inflammation, and improved rheology.

羟基脲除了诱导HbF外的额外益处包括降低中性粒细胞和血小板计数、减少炎症和改善血液流变学。

Toxicities of hydroxyurea in SCA are typically mild and predictable; modest cytopenia is expected and actually therapeutic, while occasional gastrointestinal and cutaneous manifestations are well-tolerated.

在镰状细胞贫血（SCA）中，羟基脲的毒性通常是轻微且可预测的；适度的细胞减少症是预期的，实际上是有治疗作用的，而偶尔的胃肠道和皮肤表现也是可以很好耐受的。

Long-term risks of hydroxyurea for SCA are mainly theoretical but require ongoing surveillance.

羟基脲对镰状细胞贫血(SCA)的长期风险主要是理论上的，但需要持续监测。

Accordingly, hydroxyurea should be initiated as part of standard of care, ideally in the first year of life.

因此，应将羟基脲作为标准护理的一部分开始使用，理想情况下在生命的头一年内开始。

Proper dosing of hydroxyurea is critical, aiming through stepwise dose escalation to achieve modest but safe myelosuppression, with periodic adjustments for weight gain.

适当的羟基脲剂量至关重要，通过逐步增加剂量以实现适度但安全的骨髓抑制，对于体重增加需定期调整剂量。

Precision dosing using pharmacokinetics may facilitate optimal dosing without frequent dose adjustments.

使用药物动力学进行精确剂量调整可能有助于在无需频繁调整剂量的情况下实现最佳剂量。

Although transformative and even curative therapies for SCA are emerging, hydroxyurea is the only available and accessible disease-modifying treatment that can address the global burden of disease, especially in low-resource settings within sub-Saharan Africa.

尽管针对镰状细胞贫血(SCA)的变革性甚至治愈性疗法正在出现，但羟基脲是唯一可用且可及的疾病修饰性治疗，可以应对全球疾病负担，特别是在撒哈拉以南非洲的低资源环境中。