Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
Platelets. 2013;24(3):213-8. doi: 10.3109/09537104.2012.684733. Epub 2012 May 30.
Platelet dysfunction and associated hemorrhagic complications are often encountered in patients with chronic kidney disease. This study aimed to evaluate the prevalence and associations for abnormal bleeding time (BT) in patients with renal dysfunction. Hemoglobin, hematocrit, platelet, blood urea nitrogen, creatinine, and parathyroid hormone levels were determined in 1716 patients (55.18 ± 17.19 years, men 50.8%). For these patients, BTs were estimated using a platelet function analyzer-100. Glomerular filtration rates (GFRs) were estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. The study population was divided into six groups according to the estimated GFR (eGRF): group I, eGFR ≥ 90 ml/min/1.73 m(2); group II, 60 ≤ eGFR < 90 ml/min/1.73 m(2); group III, 30 ≤ eGFR < 60 ml/min/1.73 m(2); group IV, 15 ≤ eGFR < 30 ml/min/1.73 m(2); group V, eGFR < 15 ml/min/1.73 m(2); and group VI, undergoing regular hemodialysis. Renal insufficiency was defined as eGFR < 60 ml/min/1.73 m(2). To further investigate the role of inflammatory cytokines, nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) were measured in a 327-patient subset of the total patient population (52.82 ± 18.3 years, men 60.9%). Abnormal BT occurred in 11.8% of group I, 15.3% of group II, 29.1% of group III, 37.5% of group IV, 35.0% of group V, and 32.1% of group VI. By Pearson correlation coefficient, eGFR (r = -0.089), hemoglobin (r = -0.127), platelet (r = -0.054) were correlated with BT. Multivariate analysis revealed that age [odds ratio (OR), 1.013; 95% CI, 1.004-1.022], renal insufficiency (eGFR < 60 ml/min/1.73 m(2); OR, 2.271; 95% CI, 1.672-3.083), anemia (hemoglobin < 120 g/l; OR, 1.486; 95% CI, 1.089-2.027), and thrombocytopenia (platelet < 150 × 10(9)/l; OR, 1.445; 95% CI, 1.089-1.918) were independently associated with prolonged BT. Plasma levels of NO and TNF-α were increased in patients with renal insufficiency (eGFR < 60 ml/min/1.73 m(2)). Plasma levels of NO in renal insufficiency group were higher in prolonged BT than those in normal BT. A significant positive correlation was noted between BTs and NO levels (r = 0.152, p = 0.009) but not with TNF-α levels. The prevalence of abnormal BTs was higher as eGFR declined. Old age, renal insufficiency, anemia, and thrombocytopenia were independent associations for abnormal BT.
血小板功能障碍和相关出血并发症在慢性肾脏病患者中经常遇到。本研究旨在评估肾功能障碍患者异常出血时间 (BT) 的患病率和关联。在 1716 名患者（55.18±17.19 岁，男性 50.8%）中测定血红蛋白、血细胞比容、血小板、血尿素氮、肌酐和甲状旁腺激素水平。使用血小板功能分析仪-100 估计这些患者的 BT。使用慢性肾脏病流行病学合作方程估计肾小球滤过率 (GFR)。根据估计的肾小球滤过率 (eGFR) 将研究人群分为六组：组 I，eGFR≥90 ml/min/1.73 m(2)；组 II，60≤eGFR<90 ml/min/1.73 m(2)；组 III，30≤eGFR<60 ml/min/1.73 m(2)；组 IV，15≤eGFR<30 ml/min/1.73 m(2)；组 V，eGFR<15 ml/min/1.73 m(2)；组 VI，接受定期血液透析。肾功能不全定义为 eGFR<60 ml/min/1.73 m(2)。为了进一步研究炎症细胞因子的作用，在总患者人群的 327 名亚组（52.82±18.3 岁，男性 60.9%）中测量了一氧化氮 (NO) 和肿瘤坏死因子-α (TNF-α)。I 组异常 BT 的发生率为 11.8%，II 组为 15.3%，III 组为 29.1%，IV 组为 37.5%，V 组为 35.0%，VI 组为 32.1%。通过 Pearson 相关系数，eGFR（r=-0.089）、血红蛋白（r=-0.127）和血小板（r=-0.054）与 BT 相关。多变量分析显示年龄 [比值比 (OR)，1.013；95%置信区间，1.004-1.022]、肾功能不全 (eGFR<60 ml/min/1.73 m(2)；OR，2.271；95%置信区间，1.672-3.083)、贫血 (血红蛋白<120 g/l；OR，1.486；95%置信区间，1.089-2.027) 和血小板减少症 (血小板<150×10(9)/l；OR，1.445；95%置信区间，1.089-1.918) 与延长 BT 独立相关。肾功能不全患者（eGFR<60 ml/min/1.73 m(2)）的血浆 NO 和 TNF-α 水平升高。肾功能不全组中 BT 延长的血浆 NO 水平高于 BT 正常的患者。BT 与 NO 水平呈显著正相关 (r=0.152，p=0.009)，但与 TNF-α水平无关。随着 eGFR 的下降，异常 BT 的患病率升高。年龄大、肾功能不全、贫血和血小板减少症是异常 BT 的独立相关因素。
