Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; and.
Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH.
Blood Adv. 2019 Oct 22;3(20):3170-3180. doi: 10.1182/bloodadvances.2019000193.
Sickle cell disease (SCD) is an inherited monogenic red blood cell disorder affecting millions worldwide. SCD causes vascular occlusions, chronic hemolytic anemia, and cumulative organ damage such as nephropathy, pulmonary hypertension, pathologic heart remodeling, and liver necrosis. Coagulation system activation, a conspicuous feature of SCD that causes chronic inflammation, is an important component of SCD pathophysiology. The key coagulation factor, thrombin (factor IIa [FIIa]), is both a central protease in hemostasis and thrombosis and a key modifier of inflammation. Pharmacologic or genetic reduction of circulating prothrombin in Berkeley sickle mice significantly improves survival, ameliorates vascular inflammation, and results in markedly reduced end-organ damage. Accordingly, factors both upstream and downstream of thrombin, such as the tissue factor-FX complex, fibrinogen, platelets, von Willebrand factor, FXII, high-molecular-weight kininogen, etc, also play important roles in SCD pathogenesis. In this review, we discuss the various aspects of coagulation system activation and their roles in the pathophysiology of SCD.
镰状细胞病 (SCD) 是一种遗传性单基因红细胞疾病，影响全球数百万人。SCD 导致血管阻塞、慢性溶血性贫血和累积性器官损伤，如肾病、肺动脉高压、病理性心脏重构和肝坏死。凝血系统激活是 SCD 的一个显著特征，它导致慢性炎症，是 SCD 病理生理学的一个重要组成部分。关键凝血因子凝血酶（因子 IIa [FIIa]）既是止血和血栓形成的中心蛋白酶，也是炎症的关键调节剂。在伯克利镰状细胞小鼠中，用药物或基因手段降低循环凝血酶原水平可显著提高存活率、改善血管炎症，并显著减少终末器官损伤。因此，凝血酶上下游的因子，如组织因子-FX 复合物、纤维蛋白原、血小板、血管性血友病因子、FXII、高分子量激肽原等，也在 SCD 发病机制中发挥重要作用。在这篇综述中，我们讨论了凝血系统激活的各个方面及其在 SCD 病理生理学中的作用。
