Junichi Onaya, Mamoru Kyogashima, Atsuko Sunose, Satoshi Miyauchi, Syoji
Mizuno and Katsuyuki Horie
Tokyo Research Institute, Seikagaku Corporation, 3-1253 Tateno, Higashiyamato,
Tokyo 207-0021, Japan
Abstract: Effects of dermatan sulfate (DS) on the endotoxin-induced
disseminated intravascular coagulation (DIC) rat model were compared with
those of low-molecular weight heparin (LMWH), nafamostat mesilate (NM) and
argathroban (AR). At doses of 5, 10 or 20 mg/kg/4 hr, DS significantly ameliorated
the decrease of fibrinogen (Fbg), the increase of fibrin-fibrinogen degradation
products (FDP) and except at the highest dose (20 mg/kg/4 hr), the prolongation
of thrombin clotting time (TCT). It also decreased the glomerular fibrin
deposits (%GFD) at doses of 10 or 20 mg/kg/4 hr. LMWH suppressed the decrease
of Fbg and the increase of FDP at doses of 1.4 or 2.8 mg/kg/4 hr. Only the
highest dose of LMWH suppressed the decrease of the platelet count (PL),
the prolongation of prothrombin time, and improved the %GFD. AR suppressed
the decrease of PL and improved the %GFD. At the dose required to improve
the %GFD, DS (5, 10 mg/kg/4 hr) significantly suppressed the prolongation
of TCT, which is related to the bleeding frequency, while LMWH and AR further
increased the prolongation of the TCT. These results suggest that DS has
potential as a therapeutic drug with a lower hemorrhagic risk as compared
with LMWH and AR in the treatment of DIC.
Keywords: Endotoxin, Dermatan sulfate, Disseminated intravascular coagulation,
Hemorrhagic tendency, Thrombin clotting time