We examined whether
JTV-803, a specific
activated factor X inhibitor independent of
antithrombin III (ATIII), is effective against
disseminated intravascular coagulation (
DIC) in rat models induced by
tissue factor (TF) or
lipopolysaccharides (LPS). In male Wistar rats,
DIC was induced by a 4 h infusion of
thromboplastin (3.75 U/kg) or LPS (50 mg/kg). The rats were given
JTV-803 (0.3 or 3 mg/kg, bolus intravenously) (JTV-803 groups) or
low molecular weight heparin (
LMWH groups) (200 U/kg, bolus intravenously) prior to an injection of TF or LPS. The results showed that
JTV-803 was dose-dependently effective against
DIC in both TF-induced and LPS-induced rat models. This anti-
DIC effect of
JTV-803 at higher doses was almost equivalent to that of
LMWH in both types of
DIC. Plasma ATIII activity was more prominent in the group treated with
JTV-803 than in that treated with
LMWH. None of rats died in the TF-induced
DIC model with or without
drug administration. On the contrary, seven of 22 rats died (mortality rate, 31.8%) in the LPS-induced
DIC model without
drug administration. Although the mortality rate of rats induced with LPS and treated with
LMWH was quite high (6/16, 37.5%), none of the LPS-induced rats treated with
JTV-803 died. These findings suggested that
JTV-803 can treat both TF-induced and LPS-induced
DIC models, and that this
drug has greater potential in preserving ATIII and in improving the prognosis of
DIC.