Laboratory of Hematology and Blood Bank Unit, "Attikon" University General Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Department of Hematology and Lymphoma, BMT Unit, Evangelismos General Hospital, 10676 Athens, Greece.
Int J Mol Sci. 2024 Nov 11;25(22):12104. doi: 10.3390/ijms252212104.
Paroxysmal Nocturnal Hemoglobinuria (PNH) constitutes a rare bone marrow failure syndrome characterized by hemolytic anemia, thrombotic events (TEs), and bone marrow aplasia of variable degrees. Thrombosis is one of the major clinical manifestations of the disease, affecting up to 40% of individuals with PNH. Venous thrombosis is more prevalent, affecting mainly unusual sites, such as intrabdominal and hepatic veins. TEs might be the first clinical manifestation of PNH. Complement activation, endothelial dysfunction, hemolysis, impaired bioavailability of nitric oxide, and activation of platelets and neutrophils are implicated in the pathogenesis of TEs in PNH patients. Moreover, a vicious cycle involving the coagulation cascade, complement system, and inflammation cytokines, such as interleukin-6, is established. Complement inhibitors, such as eculizumab and ravulizumab (C5 inhibitors), have revolutionized the care of patients with PNH. C5 inhibitors should be initiated in patients with PNH and thrombosis, while they constitute a great prophylactic measure for TEs in those individuals. Anticoagulants, such as warfarin and low-molecular-weight heparin, and, in selected cases, direct oral anticoagulants (DOACs) should be used in combination with C5 inhibitors in patients who develop TEs. Novel complement inhibitors are considered an alternative treatment option, especially for those who develop extravascular or breakthrough hemolysis when terminal inhibitors are administered.
阵发性睡眠性血红蛋白尿症（PNH）是一种罕见的骨髓衰竭综合征，其特征为溶血性贫血、血栓事件（TEs）和不同程度的骨髓再生障碍。血栓形成是该疾病的主要临床表现之一，影响多达 40%的 PNH 患者。静脉血栓形成更为普遍，主要影响不常见的部位，如腹部和肝静脉。TEs 可能是 PNH 的首发临床表现。补体激活、内皮功能障碍、溶血、一氧化氮生物利用度降低以及血小板和中性粒细胞的激活都与 PNH 患者的 TEs 发病机制有关。此外，还建立了涉及凝血级联、补体系统和炎症细胞因子（如白细胞介素-6）的恶性循环。补体抑制剂，如依库珠单抗和拉维珠单抗（C5 抑制剂），彻底改变了 PNH 患者的治疗方法。C5 抑制剂应在有 PNH 和血栓形成的患者中启动，同时对于这些患者来说，C5 抑制剂也是 TEs 的有效预防措施。对于发生 TEs 的患者，应联合使用抗凝剂（如华法林和低分子量肝素），并在特定情况下联合使用直接口服抗凝剂（DOACs）。新型补体抑制剂被认为是一种替代治疗选择，特别是对于那些在使用终末抑制剂时出现血管外或突破性溶血的患者。
