Short-term treatment with cholestyramine increases long-acting anticoagulant rodenticide clearance from rabbits without affecting plasma vitamin K1 levels nor blood coagulation

Abstract

Administration of high dose vitamin K1 (VK1) overcomes coagulopathy and bleeding elicited by acute poisoning with long-acting anti-coagulant rodenticides (LAARs). However, long-term (months) treatment is required due to long LAAR biological half-lives that may lead to poor compliance and recurrent coagulopathy. The half-lives of LAARs are extended by slow metabolism, and similar to warfarin, are thought to undergo enterohepatic recirculation. We now show that treatment with the bile acid sequestrant cholestyramine (CSA) administered concomitantly with VK1 decreases plasma LAAR levels and increases LAAR fecal excretion. Daily CSA treatment for 14 days did not reduce plasma VK1 levels, nor increase prothrombin time. Collectively, these data show that CSA accelerates LAAR clearance from rabbits without adverse effects on VK1 anti-coagulation, and could provide an additional therapeutic option for treatment of LAAR poisoning.

Keywords: bioterrorism; enterohepatic recirculation; feces; hemorrhage; prothrombin time; resin.