Malyszko Jolanta, Suchowierska Ewa, Malyszko Jacek S, Mysliwiec Michal
Department of Nephrology and Internal Medicine, Bialystok University School of Medicine, Bialystok, Poland.
Perit Dial Int. 2002 Sep-Oct;22(5):582-92.
Bleeding diathesis and simultaneous thrombotic complications may be seen in dialyzed patients. Erythropoietin (EPO) may shift the precarious balance of the hemostatic system toward thrombosis. Platelets and tissue factor (TF) play a major role in plug formation. Tissue factor pathway inhibitor (TFPI) appears to play a primary role in regulating TF-induced coagulation. Thrombin activatable fibrinolysis inhibitor (TAFI) is a key protein linking coagulation and fibrinolysis. The aim of the study was to assess whether 6 months of EPO therapy affects platelet function, that is, platelet aggregation and P-selectin level; moieties of the extrinsic coagulation pathway: TF, TFPI, and TFPI/Xa complexes, and factors VII and X; markers of ongoing coagulation: thrombin-antithrombin complexes (TAT) and prothrombin fragments 1+2; a marker of ongoing fibrinolysis: plasmin-antiplasmin complexes (PAP); fibrinolytic activity: euglobulin clot lysis time (ECLT); and markers of endothelial cell injury: von Willebrand factor, thrombomodulin, E-selectin, and TAFI, in continuous ambulatory peritoneal dialysis (CAPD) patients.
22 patients on CAPD were given EPO 6,000 U/week. 12 patients with chronic renal failure and 12 healthy volunteers served as control groups. All parameters were studied before, and after 1, 3, and 6 months of EPO therapy.
Department of Nephrology and Internal Medicine, Medical Academy of Bialystok, Poland.
Platelet aggregation in whole blood did not change significantly during EPO treatment. A significant rise in arachidonic acid-induced platelet aggregation in platelet-rich plasma was observed after 3 and 6 months, and in collagen-induced platelet aggregation after 6 months of EPO therapy, compared to the baseline values. The TFPI concentration decreased significantly after 6 months of EPO therapy. The activity of factor VII increased transiently after 1 month of EPO therapy, compared to the baseline values. The TAFI concentration and activity in the CAPD group were significantly higher than in the control group. Erythropoietin therapy resulted in a significant decrease in TAFI concentration and activity after 6 months of EPO treatment. The ECLT was shortened significantly as early as after 1 month of EPO therapy. Thrombomodulin, von Willebrand factor concentration and activity, PAP, TAT, TFPI/Xa complexes, prothrombin fragments 1+2, factor X activity, P-selectin, E-selectin, and lipoprotein(a) did not change significantly during EPO treatment.
Erythropoietin treatment has a minimal effect on hemostasis in CAPD patients. A tendency toward a decline in TAFI is of unknown clinical relevance so far, and awaits further research.
在接受透析的患者中可能会出现出血素质和同时发生的血栓形成并发症。促红细胞生成素(EPO)可能会使止血系统不稳定的平衡向血栓形成方向转变。血小板和组织因子(TF)在血栓形成中起主要作用。组织因子途径抑制剂(TFPI)似乎在调节TF诱导的凝血中起主要作用。凝血酶激活的纤维蛋白溶解抑制剂(TAFI)是连接凝血和纤维蛋白溶解的关键蛋白。本研究的目的是评估6个月的EPO治疗是否会影响血小板功能,即血小板聚集和P-选择素水平;外源性凝血途径部分:TF、TFPI和TFPI/Xa复合物,以及因子VII和X;正在进行的凝血标志物:凝血酶-抗凝血酶复合物(TAT)和凝血酶原片段1+2;正在进行的纤维蛋白溶解标志物:纤溶酶-抗纤溶酶复合物(PAP);纤维蛋白溶解活性:优球蛋白凝块溶解时间(ECLT);以及内皮细胞损伤标志物:血管性血友病因子、血栓调节蛋白(TM)、E-选择素和TAFI,在持续性非卧床腹膜透析(CAPD)患者中。
22例CAPD患者接受每周6000 U的EPO治疗。12例慢性肾衰竭患者和12名健康志愿者作为对照组。在EPO治疗前、治疗1、3和6个月后研究所有参数。
波兰比亚韦斯托克医学院内科和肾脏病科。
在EPO治疗期间,全血中的血小板聚集没有显著变化。与基线值相比,在EPO治疗3个月和6个月后,富含血小板血浆中花生四烯酸诱导的血小板聚集显著增加,在EPO治疗6个月后,胶原诱导的血小板聚集显著增加。EPO治疗6个月后,TFPI浓度显著降低。与基线值相比,EPO治疗1个月后,因子VII的活性短暂增加。CAPD组的TAFI浓度和活性显著高于对照组。EPO治疗6个月后,EPO治疗导致TAFI浓度和活性显著降低。早在EPO治疗1个月后,ECLT就显著缩短。在EPO治疗期间,血栓调节蛋白、血管性血友病因子浓度和活性、PAP、TAT、TFPI/Xa复合物、凝血酶原片段1+2、因子X活性、P-选择素、E-选择素和脂蛋白(a)没有显著变化。
EPO治疗对CAPD患者的止血作用最小。目前TAFI下降的趋势临床意义尚不清楚,有待进一步研究。