Misztal Tomasz, Tomasiak Marian
Zakład Chemii Fizycznej, Uniwersytet Medyczny w Białymstoku.
Postepy Hig Med Dosw (Online). 2011 Sep 28;65:627-39. doi: 10.5604/17322693.961007.
Abundant hemolysis is associated with a number of inherent and acquired diseases including sickle-cell disease (SCD), polycythemia, paroxysmal nocturnal hemoglobinuria (PNH) and drug-induced hemolytic anemia. Despite different etiopathology of hemolytic diseases, many concomitant symptoms are comparable and include e.g. hypertension, hemoglobinuria and hypercoagulation state. Studies in the last years have shown a growing list of mechanisms lying at the basis of those symptoms, in particular irreversible reaction between cell-free hemoglobin (Hb) and nitric oxide (NO) - endogenous vasorelaxant and anti-thrombotic agent. Saturation of protective physiological cell-free Hb-scavenging mechanisms results in accumulation of Hb in plasma and hemoglobinemia. Extensive hemoglobinemia subsequently leads to hemoglobinuria, which may cause kidney damage and development of Fanconi syndrome. A severe problem in patients with SCD and PNH is pulmonary and systemic hypertension. It may lead to circulation failure, including stroke, and it is related to abolition of NO bioavailability for vascular smooth muscle cells. Thrombotic events are the major cause of death in SCD and PNH. It ensues from lack of platelet inhibition evoked by Hb-mediated NO scavenging. A serious complication that affects patients with excessive hemolysis is erectile dysfunction. Also direct cytotoxic, prooxidant and proinflammatory effects of cell-free hemoglobin and heme compose the clinical picture of hemolytic diseases. The pathophysiological role of plasma Hb, mechanisms of its elimination, and direct and indirect (via NO scavenging) deleterious effects of cell-free Hb are presented in detail in this review. Understanding the critical role of hemolysis and cell-free Hb is important in the perspective of treating patients with hemolytic diseases and to design new effective therapies in future.
大量溶血与多种先天性和后天性疾病相关，包括镰状细胞病（SCD）、红细胞增多症、阵发性夜间血红蛋白尿（PNH）和药物性溶血性贫血。尽管溶血性疾病的病因病理不同，但许多伴随症状具有可比性，包括例如高血压、血红蛋白尿和高凝状态。近年来的研究表明，这些症状背后的机制越来越多，特别是游离血红蛋白（Hb）与一氧化氮（NO）——内源性血管舒张剂和抗血栓形成剂之间的不可逆反应。保护性生理游离Hb清除机制的饱和导致Hb在血浆中积累和血红蛋白血症。广泛的血红蛋白血症随后导致血红蛋白尿，这可能会导致肾损伤和范科尼综合征的发展。SCD和PNH患者的一个严重问题是肺动脉高压和系统性高血压。它可能导致循环衰竭，包括中风，并且与血管平滑肌细胞的NO生物利用度丧失有关。血栓形成事件是SCD和PNH患者死亡的主要原因。这是由于Hb介导的NO清除引起的血小板抑制缺乏所致。影响过度溶血患者的一个严重并发症是勃起功能障碍。游离血红蛋白和血红素的直接细胞毒性、促氧化和促炎作用也构成了溶血性疾病的临床表现。本文详细介绍了血浆Hb的病理生理作用、其清除机制以及游离Hb的直接和间接（通过NO清除）有害作用。从治疗溶血性疾病患者的角度以及未来设计新的有效疗法来看，了解溶血和游离Hb的关键作用非常重要。
