Thrombophilia is 1 of the principal features of paroxysmal nocturnal hemoglobinuria (PNH) and constitutes the main cause of disease morbidity/mortality. Anticomplement treatment has revolutionized the natural history of PNH, with control of the hemolytic process and abolition of thrombotic events (TEs). However, no guidelines exist for the management of thromboembolic complications in this setting, with type and duration of anticoagulation depending on individual practices. Besides, a scarcity of data is present on the efficacy of direct oral anticoagulants (DOACs). Herein, we accrued a large real-world cohort of patients with PNH from 4 US centers to explore features, predictors of TE, and anticoagulation strategies. Among 267 patients followed up for a total of 2043 patient-years, 56 (21%) developed TEs. This occurred at disease onset in 43% of cases, involving more frequently the venous system, typically as Budd-Chiari syndrome. Rate of TEs was halved in patients receiving complement inhibitors (21 vs 40 TEs per 1000 patient-years in untreated cases, with a 2-year cumulative incidence of thrombosis of 3.9% vs 18.3%, respectively), and varied according to PNH granulocytes and erythrocytes clone size, type, disease activity parameters, as well as number (≥2 mutations, or less) and variant allelic frequency of mutations. Anticoagulation with warfarin (39%), DOACs (37%), and low-molecular weight heparin (16%) was administered for a median of 29 months (9-61.8). No thrombotic recurrence was observed in 19 patients treated with DOACs at a median observation of 17.1 months (8.9-45) whereas 14 cases discontinued anticoagulation without TE recurrence at a median time of 51.4 months (29.9-86.8).

中文翻译：

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新疗法时代阵发性睡眠性血红蛋白尿相关血栓形成：2043 年患者分析

血栓形成倾向是阵发性睡眠性血红蛋白尿症 (PNH) 的主要特征之一，也是疾病发病/死亡的主要原因。抗补体治疗彻底改变了 PNH 的自然史，控制了溶血过程并消除了血栓事件 (TE)。然而，在这种情况下，尚无治疗血栓栓塞并发症的指南，抗凝治疗的类型和持续时间取决于个人实践。此外，关于直接口服抗凝剂（DOAC）功效的数据也很少。在此，我们收集了来自美国 4 个中心的大量现实世界 PNH 患者队列，以探索 TE 的特征、预测因素和抗凝策略。在总共 2043 患者年的随访中，267 名患者中有 56 名 (21%) 出现了 TE。 43% 的病例发生在疾病发作时，更频繁地累及静脉系统，通常为布加综合征。接受补体抑制剂的患者中，TE 发生率减半（未经治疗的病例中，每 1000 名患者年发生 21 例 TE，而未治疗病例中，每 1000 例患者年 40 例 TE，血栓形成的 2 年累积发生率分别为 3.9% 和 18.3%），并且根据 PNH 粒细胞和红细胞克隆大小、类型、疾病活动参数，以及突变数量（≥2 个突变或更少）和变异等位基因频率。华法林 (39%)、DOAC (37%) 和低分子量肝素 (16%) 抗凝治疗的中位时间为 29 个月 (9-61.8)。 19 例接受 DOAC 治疗的患者在中位观察时间为 17.1 个月（8.9-45）时未观察到血栓复发，而 14 例患者在中位观察时间为 51.4 个月（29.9-86.8）时停止抗凝治疗而未出现 TE 复发。