Abstract | INTRODUCTION: MATERIALS AND METHODS: Anesthetized rabbits were treated with initial 0, 75, 200 or 450 μg kg(-1) dabigatran boluses followed by continuous infusions to maintain elevated plasma dabigatran levels. At 15 min after the start of dabigatran administration, PCC doses of 0, 50 or 300 IU kg(-1) were administered. Thereafter, coagulation in an arteriovenous (AV) shunt was evaluated and histopathologic examination for thrombotic changes performed. Venous thrombosis was also assessed in a modified Wessler model. RESULTS: At the suprapharmacologic dose of 300 IU kg(-1), PCC increased thrombus weight during AV shunting, but this effect could be prevented by dabigatran at all tested doses. AV shunt occlusion after PCC administration was delayed by 75 μg kg(-1) dabigatran and abolished by progressively higher dabigatran doses. High-dose treatment with 300 IU kg(-1) PCC resulted in histologically evident low-grade pulmonary thrombi; however, that effect could be blocked by dabigatran in a dose-dependent manner (p=0.034). In rabbits treated with high-dose PCC, dabigatran inhibited thrombus formation during venous stasis. PCC effectively reversed dabigatran-induced bleeding. CONCLUSIONS:
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Authors | Eva Herzog, Franz J Kaspereit, Wilfried Krege, Baerbel Doerr, Joanne van Ryn, Gerhard Dickneite, Ingo Pragst |
Journal | Thrombosis research
(Thromb Res)
Vol. 134
Issue 3
Pg. 729-36
(Sep 2014)
ISSN: 1879-2472 [Electronic] United States |
PMID | 25084749
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014. Published by Elsevier Ltd. |
Chemical References |
- Drug Combinations
- Hemostatics
- factor IX, factor VII, factor X, prothrombin drug combination
- Factor VII
- Prothrombin
- Factor IX
- Factor X
- Thrombin
- Dabigatran
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Topics |
- Animals
- Blood Coagulation
(drug effects)
- Blood Coagulation Tests
- Dabigatran
- Disease Models, Animal
- Drug Combinations
- Factor IX
(administration & dosage, toxicity)
- Factor VII
(administration & dosage, toxicity)
- Factor X
(administration & dosage, toxicity)
- Female
- Hemorrhage
(blood, chemically induced, prevention & control)
- Hemostatics
(administration & dosage, toxicity)
- Prothrombin
(administration & dosage, toxicity)
- Rabbits
- Risk Assessment
- Risk Factors
- Thrombin
(metabolism)
- Time Factors
- Venous Thrombosis
(blood, chemically induced, prevention & control)
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