Meizothrombin, the stable intermediate product of
ecarin-induced
prothrombin conversion, was investigated for its ability to bind
hirudin in blood. After in vitro pre-incubation of rat plasma with
ecarin, the prolongation of the thrombin time caused by
hirudin was reduced. The extent of
hirudin neutralization was found to be dependent on the duration of incubation with
ecarin. In vivo, after bilateral
nephrectomy in Wistar rats and following administration of
hirudin at a dose of 1 or 5 mg/kg, the blood level of
hirudin remained constant after 2 h. After infusion of
ecarin following
hirudin administration, the
hirudin blood level dropped sharply, reaching significantly reduced values, and
bleeding stopped. Platelet count and
fibrinogen level in plasma remained unchanged in the experiments using
ecarin-induced
prothrombin conversion intermediate generation. It is concluded that
meizothrombin, a naturally occurring
prothrombin conversion intermediate, provides an effective agent to neutralize toxic blood levels of
hirudin.