Anticoagulant and antiheparin activities of a pentosan polysulphate.
Pentosan polysulphate (PPS, Hemoclar, MW 6,700) was observed to have a low affinity for ATIII-Sepharose eluting at 0.3M NaCl. Tested in vitro it had, as previously reported, a low potency as an anticoagulant, about 10 times less than heparin on a weight for weight basis. Only the KCCT was affected by low concentrations of PPS unlike heparin by which both thrombin time and KCCT were affected. Upon injection of PPS subcutaneously (50mg) the heparin activity measured by chromogenic anti factor Xa and by KCCT was in the ratio of 2:1. When injected intravenously (40mg) into 3 healthy volunteers a significant prolongation of a modified prothrombin time was observed in 2 subjects. When PPS was added to heparin containing plasma it was observed to completely inhibit heparin at low concentrations (2:1 on a weight to weight basis) when measured in the thrombin and prothrombin time but not in the KCCT. The antiheparin effect of PPS was also observed in a purified system in obviating the heparin potentiation of the rate of inhibition of thrombin by antithrombin III. Observations showed that at higher concentrations of PPS it acted by directly inhibiting thrombin without the intervention of antithrombin III but also to potentiate the rate of fibrin monomer polymerization.
D000925:Anticoagulants; D000990:Antithrombin III / Q000378:metabolism; D006494:Heparin Antagonists; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D010426:Pentosan Sulfuric Polyester / Q000008:administration & dosage / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism; D014914:Whole Blood Coagulation Time
D000925:Anticoagulants; D006494:Heparin Antagonists; D011134:Polysaccharides; D010426:Pentosan Sulfuric Polyester; D000990:Antithrombin III; D013917:Thrombin