Opatrný K
I. interní klinika LF UK a FN, Plzen.
Cas Lek Cesk. 2003;142(12):741-5.
Since the nineties of the previous century, incidence of pure red-cell aplasia (PRCA) in patients with chronic renal failure (CRF) and renal anaemia treated with recombinant human erythropoietin (rHuEPO) has significantly increased. Due to the positive effects of rHuEPO on quality of life, lowering of morbidity and mortality of patients with CRF, such increased incidence has attained a widespread interest, though PRCA remains only a rare complication. The responsibility for the development of PRCA lies with the neutralizing anti-erythropoietin antibodies. The rise of antibodies and development of PRCA is related to the subcutaneous administration of erythropoietin and in the vast majority of patients to the treatment with Eprex, one of the epoetins alpha. At present, the most probable explanation is a change of the stabilizer in Eprex formulation, which is related to the increased immunogeneity of the product. The subcutaneous administration of rHuEPO, preferred for medical and economical reasons in both American and European guidelines, is known for its higher immunization power. Properties of the product, emphasized by the route of administration, can cause the rise of these antibodies. To prevent the rise of anti-erythropoietin antibodies and the development of PRCA, regulatory authorities and Eprex producers decided that Eprex cannot be administered to CRF patients subcutaneously, but only intravenously. Also the requirements on the handling of Eprex have become more stringent. Limitations do not concern either epoetin beta (NeoRecormon) or other epoetins alpha (of which the latter are not available in this country). Therapy of PRCA in patients treated with rHuEPO is based on suspension of rHuEPO and on the immunosuppressive therapy. Many questions concerning PRCA in CRF patients treated with rHuEPO remain unsolved. It is necessary to study further the ethiopathogenesis of this complication and possibly adjust preventive and therapeutic measures.
自上世纪九十年代以来，慢性肾衰竭（CRF）患者及肾性贫血患者接受重组人促红细胞生成素（rHuEPO）治疗时，纯红细胞再生障碍性贫血（PRCA）的发病率显著上升。由于rHuEPO对CRF患者的生活质量、降低发病率和死亡率具有积极作用，尽管PRCA仍然只是一种罕见的并发症，但这种发病率的上升已引起广泛关注。PRCA的发生与中和性抗促红细胞生成素抗体有关。抗体的产生及PRCA的发生与促红细胞生成素的皮下给药有关，在绝大多数患者中与α-促红细胞生成素之一的益比奥治疗有关。目前，最可能的解释是益比奥制剂中稳定剂的改变，这与产品免疫原性增加有关。出于医学和经济原因，美国和欧洲的指南均更倾向于皮下注射rHuEPO，而皮下注射因其更高的免疫原性而闻名。给药途径所强调的产品特性可导致这些抗体的产生。为防止抗促红细胞生成素抗体的产生及PRCA的发生，监管机构和益比奥生产商决定，益比奥不能皮下注射给CRF患者，而只能静脉注射。同时，对益比奥处理的要求也变得更加严格。这些限制不适用于β-促红细胞生成素（宁红欣）或其他α-促红细胞生成素（后者在该国无法获得）。接受rHuEPO治疗的患者发生PRCA时，治疗方法是停用rHuEPO并进行免疫抑制治疗。许多关于接受rHuEPO治疗的CRF患者发生PRCA的问题仍未解决。有必要进一步研究这种并发症的发病机制，并可能调整预防和治疗措施。
