Summary
The antithrombotic and anticoagulant activities of depolymerized fragment (DHG-l)
of glycosaminoglycan extracted from Stichopw japonicus Selenka (FGAG) were compared with those of unfractionated heparin (UFH) or low molecular
weight heparin (LMWH). DHG-1 at more than 0.3 mg/kg i. v. significantly prevented
death of mice treated with thrombin (800 U/kg i.u.). Under the same conditions, FGAG,
UFH and LMWH significantly prevented death of mice at more than 0.3, 0.3 and 0.6 mg/kg
i.v., respectively. In normal plasma, the concentration required to double the activated
partial thromboplastin time (doubling APTT) of DHG-I, FGAG, LMWH and UFH were 12.0,
2.4, 5.8, and 1.2 μg/ml, respectively. In antithrombin III (AT Ill)-depleted plasma,
doubling APTT of DHG-1, FGAG, and UFH were 11.3, 2.1, and 18.5 μg/ml, respectively.
Prothrombin activation in contact-activated plasma was inhibited completely for 60
s at doubling APTT by all glycosaminoglycans used in this study. DHG-I, however, showed
much less antithrombin activity than UFH as tested by thrombin clotting time in plasma
and chromogenic assay in the presence of AT III. Moreover, DHG-1 showed much less
inhibitory activity on factor Xa, factor IXa, and glass surface-induced factor IXa
generation than UFH
These results suggested that DHG-1 is one of the promising antithrombotic agents with
quite different anticoagulant property from UFH or LMWH.
