Machleidt C, Mettang T, Stärz E, Weber J, Risler T, Kuhlmann U
Department of Nephrology, Robert-Bosch-Krankenhaus Stuttgart, Federal Republic of Germany.
Kidney Int. 1989 Dec;36(6):1119-24. doi: 10.1038/ki.1989.310.
Platelet aggregation, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF 4) release and thromboxane B2 (TxB2) formation in stimulated platelet-rich plasma were investigated in 13 patients with nephrotic syndrome who had normal serum creatinine levels (creatinine clearance greater than 70 ml/min/1.73 m2). In contrast to 13 sex- and age-matched controls, spontaneous platelet aggregation only occurred in patients with nephrotic syndrome with correlation to serum albumin and plasma fibrinogen levels. The EC50 (estimated concentration of aggregating agent to cause half maximum velocity of primary aggregation) for ADP and collagen and threshold concentration of arachidonic acid (threshold AA) were decreased in patients with nephrotic syndrome, reflecting a hyperaggregable state. In patients with nephrotic syndrome EC50 ADP values were significantly correlated to serum albumin, serum cholesterol and plasma fibrinogen, however, EC50 collagen or threshold AA did not correlate to these parameters. Plasma beta-TG levels were increased in patients, whereas plasma PF 4 levels were not significantly changed in patients compared to controls. In vitro TxB2 formation was elevated in patients only after stimulation with AA. Nevertheless, after stimulation with collagen and ADP, TxB2 formation was unchanged in patients compared to controls. Platelet hyperaggregability in nephrotic patients was confirmed in our study. However, unchanged thromboxane B2 formation after collagen stimulus as well as missing correlations between EC50 collagen or threshold AA and serum albumin were contradictory to the hypothesis that enhanced AA availability due to hypoalbuminemia is responsible for platelet hyperaggregability. Platelet hyperaggregability in terms of EC50 ADP being associated with serum albumin levels as well as to serum cholesterol and plasma fibrinogen indicate a multifactorial genesis.
对13例血清肌酐水平正常（肌酐清除率大于70 ml/min/1.73 m2）的肾病综合征患者，研究了富血小板血浆受刺激后的血小板聚集、β-血小板球蛋白（β-TG）和血小板因子4（PF 4）释放以及血栓素B2（TxB2）生成情况。与13例年龄和性别匹配的对照组相比，仅肾病综合征患者出现自发性血小板聚集，且与血清白蛋白和血浆纤维蛋白原水平相关。肾病综合征患者中，ADP和胶原的半数有效浓度（EC50，引起初始聚集最大速度一半时的聚集剂估计浓度）以及花生四烯酸的阈值浓度（阈值AA）降低，反映出高聚集状态。肾病综合征患者中，EC50 ADP值与血清白蛋白、血清胆固醇和血浆纤维蛋白原显著相关，然而，EC50胶原或阈值AA与这些参数无关。患者血浆β-TG水平升高，而与对照组相比，患者血浆PF 4水平无显著变化。仅在花生四烯酸刺激后，患者体外TxB2生成升高。然而，与对照组相比，胶原和ADP刺激后患者TxB2生成无变化。我们的研究证实了肾病患者存在血小板高聚集性。然而，胶原刺激后血栓素B2生成无变化，以及EC50胶原或阈值AA与血清白蛋白之间缺乏相关性，这与低白蛋白血症导致花生四烯酸可用性增加是血小板高聚集性原因的假设相矛盾。就EC50 ADP而言，血小板高聚集性与血清白蛋白水平以及血清胆固醇和血浆纤维蛋白原相关，表明其发病机制是多因素的。
