Lodhi Omair Ul Haq, Sohail Shaezal, Hassan Danyal
Internal Medicine, Shifa International Hospital, Islamabad, PAK.
Internal Medicine/Nephrology, Shifa International Hospital, Islamabad, PAK.
Cureus. 2020 Jun 24;12(6):e8806. doi: 10.7759/cureus.8806.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell (HSC) disorder characterized by a partial or complete deficiency of glycosyl-phosphatidylinositol (GPI)-linked membrane proteins, which leads to intravascular hemolysis. The loss of CD55 and CD59, two GPI-anchored proteins on red blood cell surfaces, from mutations in the X-linked phosphatidylinositol glycan class A (PIGA) gene, causes unrestricted proliferation of complement activation. The loss of CD59 especially leads to 'paroxysms' of acute intravascular hemolysis during events of stress. Extravascular hemolysis also occurs without CD55 as the accumulation of C3 on red blood cell surfaces leads to their destruction by the reticuloendothelial system. Diagnosis of PNH relies primarily on clinical presentation and flow cytometry assays used to detect the GPI-anchored proteins, CD55 and CD59; however, fluorescein-labeled proaerolysin variant (FLAER) is seen to have a significant advantage over CD55 and CD59. Typical symptoms of the disorder include fatigue, shortness of breath, hemoglobinuria, abdominal pain and bone marrow failure. Thrombosis also occurs secondary to nitric oxide (NO) deficiency, release of procoagulants, increased tissue factor and reduced fibrinolysis. The classification of PNH is subdivided into three types: classical, PNH with another bone marrow disorder and subclinical PNH. Management of hemolysis, thrombosis and pancytopenia is based on the pathogenesis involved. Inhibition of complement in the form of humanized monoclonal antibody against complement C5 (eculizumab) is seen as an emerging treatment option, while stem cell/bone marrow transplant may also be offered. We present a rare case of PNH with bilateral renal vein thrombosis, who was diagnosed with classical PNH on clinical presentation and flow cytometry. He was initially offered bone marrow transplantation but was lost to follow-up and later presented with bilateral renal vein thrombosis. He was managed conservatively with transfusions and anticoagulation, and was discharged for follow-up on an outpatient basis.
阵发性睡眠性血红蛋白尿（PNH）是一种获得性造血干细胞（HSC）疾病，其特征是糖基磷脂酰肌醇（GPI）连接的膜蛋白部分或完全缺乏，这会导致血管内溶血。X连锁磷脂酰肌醇聚糖A类（PIGA）基因突变导致红细胞表面两种GPI锚定蛋白CD55和CD59缺失，从而引起补体激活不受限制地增殖。尤其是CD59的缺失会导致应激事件期间急性血管内溶血的“发作”。由于红细胞表面C3的积累导致其被网状内皮系统破坏，所以在没有CD55的情况下也会发生血管外溶血。PNH的诊断主要依赖临床表现以及用于检测GPI锚定蛋白CD55和CD59的流式细胞术检测；然而，荧光素标记的前气单胞菌溶素变体（FLAER）相对于CD55和CD59具有显著优势。该疾病的典型症状包括疲劳、呼吸急促、血红蛋白尿、腹痛和骨髓衰竭。血栓形成也是由于一氧化氮（NO）缺乏、促凝剂释放、组织因子增加和纤维蛋白溶解减少继发引起的。PNH分为三种类型：经典型、合并另一种骨髓疾病的PNH和亚临床PNH。溶血、血栓形成和全血细胞减少的治疗基于所涉及的发病机制。以抗补体C5人源化单克隆抗体（依库珠单抗）形式抑制补体被视为一种新兴的治疗选择，同时也可能提供干细胞/骨髓移植。我们报告一例罕见的PNH合并双侧肾静脉血栓形成病例，该患者临床表现和流式细胞术检测诊断为经典型PNH。他最初接受了骨髓移植，但失访，后来出现双侧肾静脉血栓形成。他接受了输血和抗凝的保守治疗，随后出院进行门诊随访。
