Osunkwo Ifeyinwa, Manwani Deepa, Kanter Julie
Non-Malignant Hematology Section, The Levine Cancer Institute and Atrium Health, Charlotte, NC, USA.
Division of Pediatric Hematology and Oncology, The Children's Hospital at Montefiore, Albert Einstein College of Medicine, New York, NY, USA.
Ther Adv Hematol. 2020 Sep 29;11:2040620720955000. doi: 10.1177/2040620720955000. eCollection 2020.
Individuals with sickle cell disease (SCD) are living further into adulthood in high-resource countries. However, despite increased quantity of life, recurrent, acute painful episodes cause significant morbidity for affected individuals. These SCD-related painful episodes, also referred to as vaso-occlusive crises (VOCs), have multifactorial causes, and they often occur as a result of multicellular aggregation and vascular adherence of red blood cells, neutrophils, and platelets, leading to recurrent and unpredictable occlusion of the microcirculation. In addition to severe pain, long-term complications of vaso-occlusion may include damage to muscle and/or bone, in addition to vital organs such as the liver, spleen, kidneys, and brain. Severe pain associated with VOCs also has a substantial detrimental impact on quality of life for individuals with SCD, and is associated with increased health care utilization, financial hardship, and impairments in education and vocation attainment. Previous treatments have targeted primarily SCD symptom management, or were broad nontargeted therapies, and include oral or parenteral hydration, analgesics (including opioids), nonsteroidal anti-inflammatory agents, and various other types of nonpharmacologic pain management strategies to treat the pain associated with VOC. With increased understanding of the pathophysiology of VOCs, there are several new potential therapies that specifically target the pathologic process of vaso-occlusion. These new therapies may reduce cell adhesion and inflammation, leading to decreased incidence of VOCs and prevention of end-organ damage. In this review, we consider the benefits and limitations of current treatments to reduce the occurrence of VOCs in individuals with SCD and the potential impact of emerging treatments on future disease management.
在资源丰富的国家，镰状细胞病（SCD）患者的寿命越来越长。然而，尽管生存时间增加，但反复出现的急性疼痛发作给患者带来了严重的发病率。这些与SCD相关的疼痛发作，也称为血管闭塞性危机（VOCs），有多种因素导致，通常是由于红细胞、中性粒细胞和血小板的多细胞聚集和血管黏附，导致微循环反复且不可预测的阻塞。除了剧痛，血管闭塞的长期并发症可能包括肌肉和/或骨骼损伤，以及肝脏、脾脏、肾脏和大脑等重要器官的损伤。与VOCs相关的剧痛对SCD患者的生活质量也有重大不利影响，并与医疗保健利用率增加、经济困难以及教育和职业成就受损有关。以往的治疗主要针对SCD症状管理，或是广泛的非靶向治疗，包括口服或胃肠外补液、镇痛药（包括阿片类药物）、非甾体抗炎药以及各种其他类型的非药物疼痛管理策略，以治疗与VOC相关的疼痛。随着对VOCs病理生理学的深入了解，有几种新的潜在疗法专门针对血管闭塞的病理过程。这些新疗法可能会减少细胞黏附和炎症，从而降低VOCs的发生率并预防终末器官损伤。在本综述中，我们探讨了当前治疗在减少SCD患者中VOCs发生方面的益处和局限性，以及新兴治疗对未来疾病管理的潜在影响。
