Macconi D, Viganò G, Bisogno G, Galbusera M, Orisio S, Remuzzi G, Livio M
Mario Negri Institute for Pharmacological Research, Ospedali Riuniti di Bergamo, Italy.
Am J Kidney Dis. 1992 Apr;19(4):318-25. doi: 10.1016/s0272-6386(12)80447-1.
The bleeding tendency associated with uremia is likely due to a qualitative platelet dysfunction. So far the data available on platelet aggregation are conflicting. Since platelet-activating factor (PAF) plays a role in primary hemostasis, we studied platelet aggregation in response to PAF in 40 patients with chronic uremia on regular hemodialysis and 12 control subjects. Our results showed that in 28 of 40 uremics, platelet aggregation response to PAF was normal, whereas in the remaining 12 it was defective in that no second wave of aggregation was elicited even if the PAF concentrations were increased by a factor of 10,000. This abnormal response was peculiar to PAF and only partially related to factor(s) of plasma origin. The number of platelet PAF receptors and their affinity for the agonist were comparable in controls and "PAF-unresponsive" patients. The defective platelet aggregation in response to PAF was associated with a statistically significant reduction (P less than 0.01) in thromboxane A2 (TxA2) generation in platelet-rich plasma (PRP) challenged with PAF (10 and 100 nmol/L). When PRPs from PAF-unresponsive patients were preincubated with a stable analogue of prostaglandin endoperoxides/TxA2 U-46619, an irreversible platelet aggregation in response to PAF was obtained. Thus in a subpopulation of uremics, platelet aggregation in response to PAF is selectively abnormal as a consequence of a reduced TxA2 generation.
与尿毒症相关的出血倾向可能是由于血小板质量功能障碍所致。到目前为止，关于血小板聚集的现有数据相互矛盾。由于血小板活化因子（PAF）在初级止血中起作用，我们研究了40例接受定期血液透析的慢性尿毒症患者和12例对照受试者对PAF的血小板聚集反应。我们的结果表明，40例尿毒症患者中有28例对PAF的血小板聚集反应正常，而其余12例则有缺陷，即即使PAF浓度增加10000倍也不会引发第二波聚集。这种异常反应是PAF所特有的，并且仅部分与血浆来源的因子有关。对照组和“PAF无反应性”患者的血小板PAF受体数量及其对激动剂的亲和力相当。对PAF的血小板聚集缺陷与用PAF（10和100 nmol/L）刺激的富血小板血浆（PRP）中血栓素A2（TxA2）生成的统计学显著降低（P小于0.01）相关。当将PAF无反应性患者的PRP与前列腺素内过氧化物/TxA2 U-46619的稳定类似物预孵育时，可获得对PAF的不可逆血小板聚集。因此，在一部分尿毒症患者中，由于TxA2生成减少，对PAF的血小板聚集选择性异常。
