title: Global anticoagulant effects of a novel sulfated pentomanan oligosaccharide mixture.
abstract: PI-88 is a potent antiproliferative agent, which is developed for various indications in cancer. This agent is obtained from yeast fermentation and is primarily composed of pentamannose and tetramannose oligosaccharide units. PI-88 is capable of producing anticoagulant effects, which are mediated by heparin cofactor II. The purpose of this study was to determine the anticoagulant properties of PI-88 in native whole blood, freshly drawn from human volunteers, supplemented with PI-88 at various concentrations (0-100 microg/mL). Whole blood activated clotting time (ACT) was measured using Hemochron instruments. PI-88 produced a strong anticoagulant effect at 100 microg/mL (479.0+/-59.5 sec). This anticoagulant effect was comparable to that observed in interventional cardiology and open-heart surgery. At the lower level, PI-88 produced concentration-dependent effects on ACT. Using thromboelastographic techniques (TEG), the effect of PI-88 was measured in terms of various parameters. PI-88 produced potent anticoagulant effects in the TEG studies. At the concentration of 25 microg/mL, it produced a complete anticoagulant effect in whole blood. Whole blood samples supplemented with PI-88 showed a concentration-dependent decrease in the generation of various markers of clotting activation. These results clearly suggest that PI-88 exerts an anticoagulant effect in whole blood. Because of the low-molecular-weight nature and a novel mechanism of action, this new drug may be considered for further development, particularly in cancer patients.
authors: Department of Pathology and Pharmacology, Loyola University Medical Center, Maywood, Illinois, USA.
authors: P
authors: P
authors: Piccolo
authors: O
authors: O
authors: Iqbal
authors: M
authors: M
authors: Demir
authors: Q
authors: Q
authors: Ma
authors: R
authors: R
authors: Gerbutavicius
authors: J
authors: J
authors: Fareed
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D000970:Antineoplastic Agents; D001780:Blood Coagulation Tests; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009844:Oligosaccharides / Q000737:chemistry / Q000494:pharmacology*; D013916:Thrombelastography
chemical_list: D000925:Anticoagulants; D000970:Antineoplastic Agents; D009844:Oligosaccharides; C120158:phosphomannopentaose sulfate