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The Interaction Between the Indirect Anticoagulant Coumatetralyl and Calciferol (Vitamin D3) in Warfarin-resistant Rats (Rattus norvegicus)

The Interaction Between the Indirect Anticoagulant Coumatetralyl and Calciferol (Vitamin D3) in... Resistance to 4-hydroxycoumarin anticoagulant rodenticides has been a problem in some local foci for a number of years. One method of managing resistance could be to use synergists in conjunction with anticoagulants. We investigated the effect of administering cholecalciferol and coumatetralyl alone and in a synergistic mixture to anticoagulant-resistant rats by monitoring plasma factor X concentrations. The study showed that the efficacy of the compounds was significantly improved when they were used together. This synergistic effect led to an increased mortality in female rats that had been treated with both compounds compared to both a control group and groups of rats that had received the compounds singly. An unexpected result from this work was that cholecalciferol when given on its own to rats caused a decrease in plasma factor X concentration. We hypothesise that this effect was due to a vitamin D-induced increase in production of vitamin K-dependent proteins leading to a saturation of the carboxylation process and hence to a significant number of factor X molecules being under-carboxylated and therefore dysfunctional. It is suggested that the reduction in factor X levels is a major component of the increased efficacy of the anticoagulant/calciferol mixture and also that effects on other vitamin K-dependent proteins, e.g. matrix GLA protein, may play a role in the increased mortality seen in female rats. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Comparative Clinical Pathology Springer Journals

The Interaction Between the Indirect Anticoagulant Coumatetralyl and Calciferol (Vitamin D3) in Warfarin-resistant Rats (Rattus norvegicus)

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References (23)

Publisher
Springer Journals
Copyright
Copyright © 2002 by Springer-Verlag London Limited
Subject
Medicine & Public Health; Pathology; Hematology; Oncology
eISSN
1618-565X
DOI
10.1007/s580-002-8083-9
Publisher site
See Article on Publisher Site

Abstract

Resistance to 4-hydroxycoumarin anticoagulant rodenticides has been a problem in some local foci for a number of years. One method of managing resistance could be to use synergists in conjunction with anticoagulants. We investigated the effect of administering cholecalciferol and coumatetralyl alone and in a synergistic mixture to anticoagulant-resistant rats by monitoring plasma factor X concentrations. The study showed that the efficacy of the compounds was significantly improved when they were used together. This synergistic effect led to an increased mortality in female rats that had been treated with both compounds compared to both a control group and groups of rats that had received the compounds singly. An unexpected result from this work was that cholecalciferol when given on its own to rats caused a decrease in plasma factor X concentration. We hypothesise that this effect was due to a vitamin D-induced increase in production of vitamin K-dependent proteins leading to a saturation of the carboxylation process and hence to a significant number of factor X molecules being under-carboxylated and therefore dysfunctional. It is suggested that the reduction in factor X levels is a major component of the increased efficacy of the anticoagulant/calciferol mixture and also that effects on other vitamin K-dependent proteins, e.g. matrix GLA protein, may play a role in the increased mortality seen in female rats.

Journal

Comparative Clinical PathologySpringer Journals

Published: Jan 1, 2002

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