The pathophysiology of disease in patients with paroxysmal nocturnal hemoglobinuria.
The pathophysiology of disease in patients with paroxysmal nocturnal hemoglobinuria.
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DOI：
10.1182/asheducation-2008.1.104
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发表时间：
2008-01-01
期刊：
影响因子：
--
通讯作者：
Hiken, Jeffrey
中科院分区：
文献类型：
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作者：
Bessler, Monica;Hiken, Jeffrey
阵发性夜间血红蛋白尿（PNH）是一种获得性溶血性贫血，由x连锁PIGA基因突变的造血祖细胞扩张引起。PNH发生在骨髓衰竭的背景下。骨髓衰竭和异常细胞的存在解释了PNH患者的临床表型，包括溶血、细胞减少和血栓症。PIGA是合成糖基磷脂酰肌醇（GPI）锚定分子所必需的。因此，PNH血细胞缺乏使用这种锚定分子附着在细胞膜上的所有蛋白质。其中两种蛋白质调节细胞表面补体的激活。因此，它们的缺乏解释了PNH红细胞对补体介导的溶解的敏感性。补体介导的红细胞溶解发生在血管内，血管内溶血对这种疾病患者的发病率和死亡率有重要影响。PNH是一个突出的例子，说明如何增加对病理生理学的理解可以直接改善疾病的诊断、护理和治疗。
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia caused by the expansion of a hematopoietic progenitor cell that has acquired a mutation in the X-linked PIGA gene. PNH occurs on the background of bone marrow failure. Bone marrow failure and the presence of the abnormal cells account for the clinical phenotype of patients with PNH including hemolysis, cytopenia, and thrombophilia. PIGA is essential for the synthesis of glycosyl phosphatidylinositol (GPI) anchor molecules. PNH blood cells are therefore deficient in all proteins that use such an anchor molecule for attachment to the cell membrane. Two of these proteins regulate complement activation on the cell surface. Their deficiency therefore explains the exquisite sensitivity of PNH red blood cells to complement-mediated lysis. Complement-mediated lysis of red blood cells is intravascular, and intravascular hemolysis contributes significantly to the morbidity and mortality in patients with this condition. PNH is an outstanding example of how an increased understanding of pathophysiology may directly improve the diagnosis, care, and treatment of disease.