title: Anticoagulant mechanism of sulfonated polyisoprenes.
abstract: The influence of sulfonated polyisoprene (SPIP) on coagulation factors and human blood cells was investigated to elucidate and compare its anticoagulant mechanism with that of heparin. While the number of red cells was unaffected, the number of platelets decreased dramatically in the presence of SPIP due to aggregation. Using a synthetic peptide substrate to assay thrombin activity in the presence of its natural inhibitor, antithrombin (AT), we observed no stimulation by SPIP of AT-mediated inhibition. Nevertheless, thrombin cleavage of its natural substrate fibrinogen to fibrin peptide A was slightly inhibited. SPIP altered the electrophoretic mobility of fibrinogen and completely inhibited fibrinogen from clotting. We detected no significant influence of SPIP on factors II, VII, IX, and X, while factor XI and factors V and VIII were only slightly affected. Therefore, the main mechanism of SPIP's anticoagulant activity appears to be a strong interaction with fibrinogen and fibrin monomer, first, to prevent proteolytic conversion of the former to the latter and second, to inhibit polymerization of the fibrin monomer, once formed.
authors.affiliation: Tsukuba Research Laboratories, JSR Corporation, Tsukuba, Ibaraki, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tamada
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Murata
authors.forename: Toshio
authors.initials: T
authors.lastname: Hayashi
authors.forename: Kohei
authors.initials: K
authors.lastname: Goto
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005164:Factor IX / Q000378:metabolism; D005165:Factor V / Q000378:metabolism; D005167:Factor VII / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D005172:Factor XI / Q000378:metabolism; D005337:Fibrin / Q000737:chemistry; D005340:Fibrinogen / Q000737:chemistry; D005344:Fibrinopeptide A / Q000737:chemistry; D006801:Humans; D010455:Peptides / Q000737:chemistry; D011095:Polyethylenes / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011516:Prothrombin / Q000378:metabolism; D013450:Sulfones / Q000378:metabolism*; D013917:Thrombin / Q000737:chemistry
chemical_list: D000925:Anticoagulants; D010455:Peptides; D011095:Polyethylenes; D011108:Polymers; D013450:Sulfones; D005344:Fibrinopeptide A; D005165:Factor V; D005167:Factor VII; D011516:Prothrombin; D005164:Factor IX; D005170:Factor X; D005337:Fibrin; D005340:Fibrinogen; D005172:Factor XI; D013917:Thrombin