Prothrombin conversion intermediate effectively neutralizes toxic levels of hirudin

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 neut...

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Bibliographic Details
Published in:Thrombosis research 1995-11, Vol.80 (4), p.317-325
Main Authors: Nowak, Götz, Bucha, Elke
Format: Article
Language:English
Subjects:
Animals
Antithrombins - drug effects
Biological and medical sciences
Blood Coagulation - drug effects
Blood Coagulation - physiology
Blood. Blood coagulation. Reticuloendothelial system
ecarin
Endopeptidases - pharmacology
Enzyme Precursors - pharmacology
Female
Fibrinolytic Agents - pharmacology
Hirudin antidote
hirudin toxicity
Hirudins - antagonists & inhibitors
Male
Medical sciences
meizothrombin
Nephrectomy
Pharmacology. Drug treatments
Prothrombin - drug effects
Prothrombin - metabolism
prothrombin conversion intermediate
Rats
Rats, Wistar
Thrombin - pharmacology
Thrombin Time
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Summary: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.
ISSN:0049-3848
1879-2472
DOI:10.1016/0049-3848(95)00182-Q