Sickle Cell Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and.
Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA.
Blood. 2022 May 19;139(20):3030-3039. doi: 10.1182/blood.2021013873.
Chronic hemolytic anemia and intermittent acute pain episodes are the 2 hallmark characteristics of sickle cell disease (SCD). Anemia in SCD not only signals a reduction of red cell mass and oxygen delivery, but also ongoing red cell breakdown and release of cell-free hemoglobin, which together contribute to a number of pathophysiological responses and play a key role in the pathogenesis of cumulative multiorgan damage. However, although anemia is clearly associated with many detrimental outcomes, it may also have an advantage in SCD in lowering risks of potential viscosity-related complications. Until recently, clinical drug development for SCD has predominantly targeted a reduction in the frequency of vaso-occlusive crises as an endpoint, but increasingly, more attention is being directed toward addressing the contribution of chronic anemia to poor outcomes in SCD. This article aims to explore the complex pathophysiology and mechanisms of anemia in SCD, as well as the need to balance the benefits of raising hemoglobin levels with the potential risks of increasing blood viscosity, in the context of the current therapeutic landscape for anemia in SCD.
慢性溶血性贫血和间歇性急性疼痛发作是镰状细胞病（SCD）的两个主要特征。SCD 中的贫血不仅表明红细胞数量和氧气输送减少，而且还伴随着持续的红细胞破坏和无细胞血红蛋白的释放，这些共同导致了许多病理生理反应，并在累积多器官损伤的发病机制中发挥关键作用。然而，尽管贫血与许多不良后果明显相关，但它在 SCD 中也可能具有降低潜在黏度相关并发症风险的优势。直到最近，SCD 的临床药物研发主要以降低血管阻塞性危象的频率作为终点，但越来越多的注意力开始转向解决慢性贫血对 SCD 不良结局的影响。本文旨在探讨 SCD 中贫血的复杂病理生理学和机制，以及在 SCD 贫血的当前治疗领域中，需要平衡提高血红蛋白水平的益处与增加血液黏度的潜在风险。
