Efficacy of prothrombin complex concentrate to reverse the anticoagulant effect of the pentasaccharide fondaparinux in a rabbit model

Anne Godier; Marion Durand; Joseph Emmerich; Blandine Dizier; Thomas Lecompte; Charles-Marc Samama

doi:10.1160/TH10-07-0434

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 105(01): 161-168
DOI: 10.1160/TH10-07-0434

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Efficacy of prothrombin complex concentrate to reverse the anticoagulant effect of the pentasaccharide fondaparinux in a rabbit model

Anne Godier

¹INSERM U765, Paris, France

²Department of Anaesthesia and Critical Care, Paris Descartes University, Hôtel-Dieu Hospital, Paris, France

,

Marion Durand

³Department of Thoracic Surgery, Nancy University Hospital, CHU, Nancy, France

⁴INSERM U961, Nancy, France

,

Joseph Emmerich

¹INSERM U765, Paris, France

,

Blandine Dizier

¹INSERM U765, Paris, France

,

Thomas Lecompte

⁴INSERM U961, Nancy, France

⁵Laboratory of Haemostasis, Nancy University Hospital, CHU, Nancy, France

,

Charles-Marc Samama

¹INSERM U765, Paris, France

²Department of Anaesthesia and Critical Care, Paris Descartes University, Hôtel-Dieu Hospital, Paris, France

› Author Affiliations

Abstract

Summary

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 thrombelasto-metric 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.

Keywords

Arterial thrombosis - coagulation factors - haemostasis - animal models - coagulation inhibitors

Full Text

References

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