Department of Medicine, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.
Platelets. 1992;3(1):47-52. doi: 10.3109/09537109209013168.
Recombinant human erythropoietin is a successful treatment for the anaemia of renal failure. Its use has however been associated with thromboembolic complications. Changes in platelet number and behaviour in vitro were studied in: (1) 23 haemodialysis patients, and 10 continuous ambulatory peritoneal dialysis patients (CAPD) treated with erythropoietin (EPO); (2) 14 untreated dialysis patients (7 haemodialysis, 7 CAPD), with intrinsically high haemoglobins; and (3) 23 age-matched non-uraemic normal controls. All patients treated with erythropoietin had a significant rise in haemoglobin (23 haemodialysis patients: pre-EPO median (range), 6.9 (5.1-8.1)g/dl; post-EPO, 10.9 (9.0--12.8)g/dl; 10 CAPD patients: pre-EPO, 7.8 (6.7-8.8)g/dl); post-EPO, 12.5 (9.9-14.3)g/dl; p < 0.01). Platelet number was significantly reduced in CAPD patients (pre-EPO: 327 (210-745) & 10(9)/1; post-EPO: 240(198-359) & 10(9)/l; p < 0.01) but not in haemodialysis patients. Spontaneous and collagen-induced whole blood platelet aggregation were significantly increased following erythropoietin treatment, both in haemodialysis (spontaneous platelet aggregation: pre-EPO, 39(12-78)%; post-EPO, 64(27-93)%, p < 0.01, collagen-induced platelet aggregation: pre-EPO, 61(3-95)%; post-EPO, 74(21-93)% p < 0.05), and CAPD patients (spontaneous platelet aggregation: pre-EPO, 38(18-81)%; post-EPO, 71 (41-95)%, p < 0.01, collagen-induced platelet aggregation; pre-EPO, 73(28-95)%; post-EPO, 90(44-95)%, p < 0.05). There was no significant change in aggregation to 1 μM ADP. Spontaneous and collagen-induced platelet aggregation were significantly higher in erythropoietin treated patients and untreated CAPD controls with high haemoglobins compared to age and haemoglobin-matched non-uraemic normal individuals (23 normals: spontaneous platelet aggregation, 37(10-75)%; collagen-induced platelet aggregation, 43(6-94)%, p < 0.001). Enhanced platelet aggregability is associated with vascular disorders. The increased red cell mass due to erythropoietin therapy may have physical and chemical effects on platelet function predisposing to thrombosis in this susceptible group of patients.
重组人红细胞生成素是治疗肾衰竭贫血的有效方法。然而,它的使用与血栓栓塞并发症有关。研究了体外血小板数量和行为的变化:(1)23 名血液透析患者和 10 名接受红细胞生成素(EPO)治疗的持续非卧床腹膜透析患者(CAPD);(2)14 名未接受 EPO 治疗的透析患者(7 名血液透析患者,7 名 CAPD),血红蛋白较高;和(3)23 名年龄匹配的非尿毒症正常对照者。所有接受 EPO 治疗的患者血红蛋白均显著升高(23 名血液透析患者:EPO 前中位数(范围),6.9(5.1-8.1)g/dl;EPO 后,10.9(9.0-12.8)g/dl;10 名 CAPD 患者:EPO 前,7.8(6.7-8.8)g/dl;EPO 后,12.5(9.9-14.3)g/dl;p <0.01)。CAPD 患者血小板数量显著减少(EPO 前:327(210-745)&10(9)/1;EPO 后:240(198-359)&10(9)/l;p <0.01),但血液透析患者无变化。EPO 治疗后,血液透析(自发性血小板聚集:EPO 前,39(12-78)%;EPO 后,64(27-93)%,p <0.01,胶原诱导血小板聚集:EPO 前,61(3-95)%;EPO 后,74(21-93)%,p <0.05)和 CAPD 患者(自发性血小板聚集:EPO 前,38(18-81)%;EPO 后,71(41-95)%,p <0.01,胶原诱导血小板聚集;EPO 前,73(28-95)%;EPO 后,90(44-95)%,p <0.05)自发性和胶原诱导的血小板聚集明显增加。对 1 μM ADP 的聚集没有明显变化。与年龄和血红蛋白匹配的非尿毒症正常个体相比,接受 EPO 治疗的患者和未经治疗的 CAPD 对照组中血红蛋白较高的患者自发性和胶原诱导的血小板聚集明显更高(23 名正常个体:自发性血小板聚集,37(10-75)%;胶原诱导的血小板聚集,43(6-94)%,p <0.001)。增强的血小板聚集性与血管疾病有关。EPO 治疗引起的红细胞质量增加可能对血小板功能产生物理和化学影响,使这一易感患者群体易发生血栓形成。