Virshup D M, Zinkham W H, Sirota R L, Caughey W S
Am J Hematol. 1983 Jun;14(4):315-24. doi: 10.1002/ajh.2830140402.
Phenazopyridine (PAP) causes a hemolytic anemia in normal individuals who receive an overdose or in patients with decreased renal function given therapeutic doses. There are no reports of PAP-induced hemolysis in individuals with unstable hemoglobins. Therapeutic doses of PAP administered to a subject with Hb Zürich (His E7 (63) beta leads to Arg) caused a severe hemolytic anemia with many large Heinz bodies appearing in the red cells. Incubation of whole blood from three asymptomatic Hb Zürich subjects with PAP at a molar ratio of PAP/Hb of 1.3/1 produced a moderate to marked increase in methemoglobin (MHb) and Heinz body formation accompanied by a slight to moderate decrease in levels of reduced glutathione. The rates of MHb formation were proportional to the concentration of PAP. In two of the subjects the rates of formation of Heinz bodies and MHb were substantially higher than in the third subject. Red cells from five normal adults were not affected. In Hb Zürich red cells the affinity of the abnormal beta chain for carbon monoxide is much greater than that of the normal alpha and beta chains. The two subjects with higher rates of MHb and Heinz body formation were nonsmokers with in vivo carboxyhemoglobin (HbCO) levels of 4-6%. The third subject with low rates of MHb and Heinz body formation was a smoker with in vivo HbCO levels of 15-18%. Increasing levels of HbCO from 8.2% to 14.3% by the in vitro addition of CO caused a marked reduction in the rate of Heinz body formation and a moderate decrease in MHb formation. Rates of MHb formation similar to those observed in normal red cells occurred at HbCO percentages of 89.2 and 99.2. Red cells containing Hb Zürich are extremely sensitive to oxidative injury by PAP, either in vivo or in vitro. The degree of oxidative injury diminishes as the level of HbCO increases, a phenomenon that is enhanced by preferential binding of CO to the abnormal beta subunit of Hb Zürich.
非那吡啶（PAP）在接受过量药物的正常个体或接受治疗剂量的肾功能减退患者中会引发溶血性贫血。目前尚无关于PAP诱导不稳定血红蛋白个体发生溶血的报道。给一名患有苏黎世血红蛋白（His E7(63)β突变为Arg）的受试者施用治疗剂量的PAP，导致了严重的溶血性贫血，红细胞中出现了许多大的海因茨小体。将三名无症状的苏黎世血红蛋白受试者的全血与PAP以PAP/Hb摩尔比1.3/1进行孵育，高铁血红蛋白（MHb）和海因茨小体形成出现中度到显著增加，同时还原型谷胱甘肽水平略有到中度下降。MHb形成速率与PAP浓度成正比。在两名受试者中，海因茨小体和MHb的形成速率显著高于第三名受试者。来自五名正常成年人的红细胞未受影响。在苏黎世血红蛋白红细胞中，异常β链对一氧化碳的亲和力远大于正常α链和β链。两名MHb和海因茨小体形成速率较高的受试者为非吸烟者，体内碳氧血红蛋白（HbCO）水平为4 - 6%。第三名MHb和海因茨小体形成速率较低的受试者为吸烟者，体内HbCO水平为15 - 18%。通过体外添加CO使HbCO水平从8.2%增加到14.3%，导致海因茨小体形成速率显著降低，MHb形成速率中度下降。在HbCO百分比为89.2和99.2时，出现了与正常红细胞中观察到的类似的MHb形成速率。含有苏黎世血红蛋白的红细胞对PAP的氧化损伤极为敏感，无论是在体内还是体外。随着HbCO水平升高，氧化损伤程度降低，这一现象因CO优先结合到苏黎世血红蛋白的异常β亚基而增强。
