Pawlak Krystyna, Pawlak Dariusz, Mysliwiec Michal
Department of Nephrology and Clinical Transplantation, Medical University, 14 Zurawia St, 15-540 Bialystok, Poland.
Thromb Res. 2008;121(6):787-91. doi: 10.1016/j.thromres.2007.07.017. Epub 2007 Sep 14.
Recombinant human erythropoietin (rHuEPO) is the cornerstone of anaemia therapy in uraemic patients however the effects of this hormone on fibrinolytic system are difficult to interpret.
Assessment of fibrinolytic parameters: tissue-type plasminogen activator (tPA) antigen, urokinase-type plasminogen activator (uPA) and its soluble receptor (suPAR), plasminogen activator inhibitor 1 (PAI-1) and plasmin/antiplasmin (PAP) complexes were performed in haemodialyzed (HD) patients without rHuEPO therapy: Group I (n=8, Hg<10 g/dl); Group II (n=12, Hg>10 g/dl); and in HD patients treated with rHuEPO for more than 6 months (Group III, n=10) or for more than 12 months (Group IV, n=9) in relation to the healthy controls.
Patients of Group I had the significantly lower haematological parameters than those of Groups II, III and IV. All the fibrinolytic parameters studied, except PAI-1, were significantly higher in HD patients without rHuEPO therapy when compared to the controls. There were no significant differences in fibrinolytic system between the Groups I and II. Erythropoietin therapy resulted in progressive decrease in antigenic tPA levels, which reach normal range values after 6 months rHuEPO administration. uPA and PAP concentrations were also decreased and reached normal values after 12 months of rHuEPO therapy. In these patients a significant decrease in uPAR levels was also observed. Therapy with rHuEPO did not alter PAI-1 concentrations in HD patients.
These results suggest that long-term rHuEPO therapy can correct fibrinolytic parameters in patients undergoing regular HD irrespective from haemoglobin levels and in the absence of concomitant iron supplementation.
重组人促红细胞生成素(rHuEPO)是尿毒症患者贫血治疗的基石,然而这种激素对纤溶系统的影响难以解释。
纤溶参数评估:对未接受rHuEPO治疗的血液透析(HD)患者进行组织型纤溶酶原激活物(tPA)抗原、尿激酶型纤溶酶原激活物(uPA)及其可溶性受体(suPAR)、纤溶酶原激活物抑制剂1(PAI-1)和纤溶酶/抗纤溶酶(PAP)复合物的检测:第一组(n = 8,血红蛋白<10 g/dl);第二组(n = 12,血红蛋白>10 g/dl);以及与健康对照相比,接受rHuEPO治疗超过6个月(第三组,n = 10)或超过12个月(第四组,n = 9)的HD患者。
第一组患者的血液学参数显著低于第二组、第三组和第四组。与对照组相比,未接受rHuEPO治疗的HD患者中,除PAI-1外,所有研究的纤溶参数均显著更高。第一组和第二组之间的纤溶系统无显著差异。促红细胞生成素治疗导致抗原性tPA水平逐渐降低,在给予rHuEPO 6个月后达到正常范围值。uPA和PAP浓度也降低,并在rHuEPO治疗12个月后达到正常值。在这些患者中还观察到uPAR水平显著降低。rHuEPO治疗未改变HD患者的PAI-1浓度。
这些结果表明,长期rHuEPO治疗可纠正接受定期HD治疗患者的纤溶参数,无论血红蛋白水平如何,且无需同时补充铁剂。