Painful vaso-occlusive crisis (VOC) remains the most common reason for presenting to the Emergency Department and hospitalization in patients with sickle cell disease (SCD). Although two new agents have been approved by the Food and Drug Administration for treating SCD, they both target to reduce the frequency of VOC. Results from studies investigating various approaches to treat and shorten VOC have so far been generally disappointing. In this paper, we will summarize the complex pathophysiology and downstream events of VOC and discuss the likely reasons for the disappointing results using monotherapy. We will put forward the rationale for exploring some of the currently available agents to either protect erythrocytes un-involved in the hemoglobin polymerization process from sickling induced by the secondary events, or a multipronged combination approach that targets the complex downstream pathways of VOC.

中文翻译：

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镰状细胞病的血管闭塞危机：继发事件的恶性循环

痛苦的血管闭塞危象 (VOC) 仍然是镰状细胞病 (SCD) 患者就诊和住院的最常见原因。尽管美国食品和药物管理局已经批准了两种用于治疗 SCD 的新药物，但它们都旨在降低 VOC 的发生频率。迄今为止，调查各种处理和缩短 VOC 方法的研究结果普遍令人失望。在本文中，我们将总结 VOC 的复杂病理生理学和下游事件，并讨论单药治疗结果令人失望的可能原因。我们将提出探索一些目前可用的药物的基本原理，以保护未参与血红蛋白聚合过程的红细胞免受继发性事件引起的镰状化，