Study of low molecular weight heparin effect on the relation between anticoagulant activity and antithrombin III affinity.
Low molecular weight heparin (FR-860), and conventional unfractionated heparin (UF-heparin) were fractionated by rabbit antithrombin III (AT III)-Sepharose, and the effects of each affinity fraction on the coagulation and fibrinolytic activities were investigated. FR-860 was fractionated to no-affinity, low-affinity (LA) and high-affinity (HA) fractions, and UF-heparin to LA and HA fractions. The HA fractions showed higher activities regarding the prolongation of activated partial thromboplastin time, anti-factor Xa activity and antithrombin activity compared with those of LA. The HA and LA fractions exhibited the enhancement of heparin cofactor II (HC II) activity and fibrinolytic activity in a dose-dependent manner. These results suggest that the antithrombotic activity of FR-860 is exerted through AT III and other mechanism such as HC II-mediated system.
Hamano
S
S
Pharmacological Laboratories, Kissei Pharmaceutical Co. Ltd., Hotaka, Japan.
Nishiyama
M
M
Kikuchi
S
S
Komatsu
H
H
Miyata
H
H
Ikeda
S
S
Sakuragawa
N
N
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D000990:Antithrombin III / Q000378:metabolism*; D001777:Blood Coagulation / Q000187:drug effects*; D005591:Chemical Fractionation; D002846:Chromatography, Affinity; D002863:Chromogenic Compounds; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006493:Heparin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015844:Heparin Cofactor II / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D009842:Oligopeptides / Q000378:metabolism; D010314:Partial Thromboplastin Time; D010958:Plasminogen / Q000378:metabolism; D011817:Rabbits; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
D000925:Anticoagulants; D002863:Chromogenic Compounds; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D009842:Oligopeptides; C018788:valyl-leucyl-lysine 4-nitroanilide; D015844:Heparin Cofactor II; D000990:Antithrombin III; D010958:Plasminogen; D006493:Heparin; D014568:Urokinase-Type Plasminogen Activator