Differential inhibition of thrombin generation by vitamin K antagonists alone and associated with low-molecular-weight heparin

Grigoris T. Gerotziafas; Charlotte Dupont; Alex C. Spyropoulos; Mohamed Hatmi; Meyer M. Samama; Dimitris Kiskinis; Ismail Elalamy

doi:10.1160/TH08-10-0653

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 102(01): 42-48
DOI: 10.1160/TH08-10-0653

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Differential inhibition of thrombin generation by vitamin K antagonists alone and associated with low-molecular-weight heparin

Grigoris T. Gerotziafas

¹Service d’Hématologie Biologique, Hôpital Tenon, Assistance Publique Hôpitaux de Paris, France

²ER2UPMC, Faculty of Medicine, University Pierre and Marie Curie (Paris VI), France

,

Charlotte Dupont

¹Service d’Hématologie Biologique, Hôpital Tenon, Assistance Publique Hôpitaux de Paris, France

,

Alex C. Spyropoulos

³Clinical Thrombosis Center, Lovelace Medical Center, Albuquerque, New Mexico, USA

,

Mohamed Hatmi

⁴Service d’Hématologie Biologique, Hôpital Hôtel Dieu, Assistance Publique Hôpitaux de Paris, Université Pierre et Marie Curie (Paris VI), France

,

Meyer M. Samama

⁴Service d’Hématologie Biologique, Hôpital Hôtel Dieu, Assistance Publique Hôpitaux de Paris, Université Pierre et Marie Curie (Paris VI), France

,

Dimitris Kiskinis

⁵Research Unit of Thrombosis and Vascular Biology, 1st Department of Surgery, Aristotle University of Thessaloniki, Papageorgiou general Hospital, Thessaloniki, Greece

,

Ismail Elalamy

¹Service d’Hématologie Biologique, Hôpital Tenon, Assistance Publique Hôpitaux de Paris, France

²ER2UPMC, Faculty of Medicine, University Pierre and Marie Curie (Paris VI), France

› Author Affiliations

Abstract

Summary

Vitamin K antagonists (VKA) treatment starts with co-administration of low-molecular-weight heparin (LMWH). The anticoagulation induced by the two drugs is still not well determined. In the present study we used thrombin generation assay to evaluate the hypo-coagulation induced by treatment with VKA and by the combination of VKA with LMWH. Tissue factor triggered thrombin generation in platelet-poor plasma was assessed in samples from 15 healthy volunteers, 97 samples from patients treated with VKA and 41 samples from patients receiving enoxaparin and VKA. Patients were classified according to international normalised ratio (INR) level (<2, 2–3 and >3).In plasma samples from patients treated with VKA having INR 2–3 the inhibition of thrombin generation reached 50% compared to controls. In samples with INR>3 this inhibition was 80%. In samples from patients receiving both LMWH and VKA, thrombin generation was significantly decreased compared to the controls and VKA group. In samples with an INR 2–3 obtained from patients treated with LMWH and VKA, the inhibition of thrombin generation was similar to that observed in samples with an INR>3 obtained from VKA treated patients. Thrombin generation assay is sensitive to detect the global the anticoagulant effect produced by the association of LMWH and VKA. For equal INR dual anticoagulant treatment induces significantly more profound inhibition of thrombin generation compared to treatment with VKA alone. The clinical relevance of this observation merits to be studied in prospective studies in patients with defined indications of anticoagulant therapy.

Keywords

Oral anticoagulants - vitamin K antagonists - bridging treatment - LMWH - thrombin generation

Full Text

References

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