Pentosane polysulfate: the effect on hemostasis of a continuous 3-day infusion.
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.
D
D
de Prost
C
C
Guérot
F
F
Karsenty
D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000378:metabolism; D001779:Blood Coagulation Factors / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D015951:Factor Xa; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010426:Pentosan Sulfuric Polyester / Q000008:administration & dosage* / Q000494:pharmacology; D010976:Platelet Count; D011134:Polysaccharides / Q000008:administration & dosage*; D011517:Prothrombin Time; D013918:Thrombin Time
D001779:Blood Coagulation Factors; D011134:Polysaccharides; D010426:Pentosan Sulfuric Polyester; D000990:Antithrombin III; D005170:Factor X; D015951:Factor Xa