de Prost D, Guérot C, Karsenty F
Clin Pharmacol Ther. 1985 Aug;38(2):171-5. doi: 10.1038/clpt.1985.154.
Pentosane polysulfate (PP) is a sulfated polysaccharide known to exhibit anticoagulant properties that are in part independent of antithrombin III activity. These effects have only been studied in vitro or after single injections in healthy subjects. Our objective was to evaluate the modification of hemostasis induced by a 3-day continuous infusion of PP (4 mg/kg body weight/24 hr) in 10 subjects. No hemorrhagic complication was observed in any patient. Bleeding time was not modified by the infusion, despite a slight decrease in the platelet number. Among the other parameters measured, the automated partial thromboplastin time, prothrombin time, and anti-Xa activity were the most affected by PP. The kinetics of their modifications were quite uniform: clotting times and the anti-Xa effect increased gradually until reaching steady state 24 hours after the start of the infusion. A progressive return to the pretreatment level was then observed during the 6 hours after the end of the infusion. A significant decrease in the factor V concentration was found at day 4. Finally, in contrast with other reported results, no activation of fibrinolysis was induced by PP under the conditions we used, which suggests that discontinuous administration or the route of administration of the drug influences the fibrinolytic effect. In conclusion, we show the excellent tolerance of continuous infusion of PP, detail the modifications in biologic parameters of hemostasis during and after PP infusion, and demonstrate that PP decreases factor V activity.
戊聚糖多硫酸酯(PP)是一种硫酸化多糖,已知具有部分独立于抗凝血酶III活性的抗凝特性。这些作用仅在体外或在健康受试者单次注射后进行过研究。我们的目的是评估10名受试者连续3天输注PP(4mg/kg体重/24小时)诱导的止血变化。未观察到任何患者出现出血并发症。尽管血小板数量略有减少,但输注并未改变出血时间。在测量的其他参数中,自动部分凝血活酶时间、凝血酶原时间和抗Xa活性受PP影响最大。它们的变化动力学相当一致:凝血时间和抗Xa效应逐渐增加,直到输注开始后24小时达到稳态。然后在输注结束后的6小时内观察到逐渐恢复到预处理水平。在第4天发现因子V浓度显著降低。最后,与其他报道结果相反,在我们使用的条件下,PP未诱导纤维蛋白溶解激活,这表明药物的间断给药或给药途径会影响纤维蛋白溶解作用。总之,我们展示了PP连续输注的良好耐受性,详细描述了PP输注期间和之后止血生物学参数的变化,并证明PP会降低因子V活性。