Document Detail


Efficacy of prothrombin complex concentrate to reverse the anticoagulant effect of the pentasaccharide fondaparinux in a rabbit model.
MedLine Citation:
PMID:  20941458     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
As a potent anticoagulant agent, fondaparinux exposes a risk of bleeding. An effective way to reverse its effects is needed. It was the objective to study efficacy and safety of prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of fondaparinux in a rabbit model of bleeding and thrombosis. In anaesthetised and ventilated rabbits, the Folts model was applied: a stenosis (75%) and an injury were carried out on the carotid artery, inducing thrombosis. Blood flow decreased as thrombus size increased until the pressure gradient was such that the thrombus was released and local blood flow was suddenly restored. This is known as a cyclic flow reduction (CFR). After the first CFR, rabbits were randomised into three groups: control (saline and saline after 1 minute), fondaparinux (fondaparinux [3 mg.kg-1] and saline), PCC (fondaparinux and PCC [40 UI.kg-1]). Then CFRs were recorded over 20 minutes. The following were measured: ear immersion bleeding time (BT), haemoglobin blood level (Hb1) and thrombelastometric parameters (ROTEM®). Finally, a hepatosplenic section was performed; 15 minutes later, the amount of blood loss was recorded as primary endpoint and Hb2 was measured. Blood loss was increased with fondaparinux and normalised with PCC. Regarding ROTEM® INTEM, fondaparinux increased clotting time and clotting formation time. PCC normalised these parameters. EXTEM and FIBTEM tests were not modified. Regarding safety, PCC did not increase CFRs. PCC reduced bleeding without increasing thrombosis and was effective to reverse the haemorrhagic effect of fondaparinux in this rabbit model.
Authors:
Anne Godier; Marion Durand; Joseph Emmerich; Blandine Dizier; Thomas Lecompte; Charles-Marc Samama
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Publication Detail:
Type:  Journal Article     Date:  2010-10-12
Journal Detail:
Title:  Thrombosis and haemostasis     Volume:  105     ISSN:  0340-6245     ISO Abbreviation:  Thromb. Haemost.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-04     Completed Date:  2011-05-18     Revised Date:  2011-05-23    
Medline Journal Info:
Nlm Unique ID:  7608063     Medline TA:  Thromb Haemost     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  161-8     Citation Subset:  IM    
Affiliation:
Department of Anesthesia and Critical Care, Paris Descartes University; Hôtel-Dieu, Paris, France. anne.godier@htd.aphp.fr
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticoagulants / pharmacology
Blood Coagulation Factors / adverse effects,  pharmacology*,  therapeutic use
Carotid Arteries
Disease Models, Animal
Hemorrhage / chemically induced
Polysaccharides / adverse effects,  pharmacology*,  therapeutic use
Rabbits
Regional Blood Flow
Thrombosis / drug therapy*
Treatment Outcome
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/Blood Coagulation Factors; 0/Polysaccharides; 0/fondaparinux; 37224-63-8/prothrombin complex concentrates

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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