Possible role of platelet activating factor (PAF) in disseminated intravascular coagulation (DIC), evidenced by use of a PAF antagonist, CV-3988.
The i.v. infusion of endotoxin (ET) (0.25 mg/kg/hr for 4 hr) induced disseminated intravascular coagulation (DIC) in rats; thrombocytopenia, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT), hypofibrinogenemia and elevated levels of fibrinogen/fibrin degradation products (FDP) were observed. Platelet activating factor (PAF) (8 micrograms/kg/hr for 4 hr) also induced DIC-like changes, except in platelets. A specific PAF antagonist, CV-3988 (2 mg/kg bolus 5 min before ET + 1 or 2 mg/kg/hr for 4 hr of ET infusion) improved all the parameters that had been altered by both ET and PAF. CV-3988 (2 mg/kg bolus 2 hr after ET + 2 mg/kg/hr for 2 hr of ET infusion) also had beneficial effects on DIC. CV-3988 itself had no effects on the parameters of DIC. These results strongly suggest that PAF may play a role in the pathogenesis of DIC and CV-3988 may prove to be useful for the treatment of DIC.
D000818:Animals; D004211:Disseminated Intravascular Coagulation / Q000209:etiology / Q000503:physiopathology*; D004731:Endotoxins / Q000633:toxicity; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D013844:Thiazoles / Q000494:pharmacology*
D004731:Endotoxins; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D013844:Thiazoles; C037913:CV 3988