Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA; and Comprehensive Bone Marrow Failure Center, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA.
Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):143-152. doi: 10.1182/hematology.2021000245.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired blood disease caused by somatic mutations in the phosphatidylinositol glycan class A (PIGA) gene required to produce glycophosphatidyl inositol (GPI) anchors. Although PNH cells are readily identified by flow cytometry due to their deficiency of GPI-anchored proteins, the assessment of the clinical significance of a PNH clone is more nuanced. The interpretation of results requires an understanding of PNH pathogenesis and its relationship to immune-mediated bone marrow failure. Only about one-third of patients with PNH clones have classical PNH disease with overt hemolysis, its associated symptoms, and the highly prothrombotic state characteristic of PNH. Patients with classical PNH benefit the most from complement inhibitors. In contrast, two-thirds of PNH clones occur in patients whose clinical presentation is that of bone marrow failure with few, if any, PNH-related symptoms. The clinical presentations are closely associated with PNH clone size. Although exceptions occur, bone marrow failure patients usually have smaller, subclinical PNH clones. This review addresses the common scenarios that arise in evaluating the clinical significance of PNH clones and provides practical guidelines for approaching a patient with a positive PNH result.
阵发性睡眠性血红蛋白尿症（PNH）是一种后天获得性血液疾病，由磷脂酰肌醇聚糖 A（PIGA）基因的体细胞突变引起，该基因对于产生糖基磷脂酰肌醇（GPI）锚定物是必需的。虽然 PNH 细胞由于缺乏 GPI 锚定蛋白，很容易通过流式细胞术来识别，但评估 PNH 克隆的临床意义更为复杂。结果的解释需要了解 PNH 的发病机制及其与免疫介导的骨髓衰竭的关系。只有大约三分之一的 PNH 克隆患者患有典型的 PNH 疾病，表现为明显的溶血、相关症状以及 PNH 特有的高度血栓形成状态。典型 PNH 患者从补体抑制剂中获益最多。相比之下，三分之二的 PNH 克隆发生在表现为骨髓衰竭且仅有少数（如果有的话）与 PNH 相关的症状的患者中。临床表现与 PNH 克隆大小密切相关。尽管存在例外情况，但骨髓衰竭患者通常具有较小的、亚临床的 PNH 克隆。这篇综述讨论了在评估 PNH 克隆的临床意义时出现的常见情况，并为处理 PNH 阳性结果的患者提供了实用的指导方针。
