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Recombinant factor VIIa reverses the anticoagulant effect of the long‐acting pentasaccharide idraparinux in healthy volunteers
Author(s) -
Bijsterveld Nick R.,
Vink Roel,
Van Aken Benien E.,
Fennema Hein,
Peters Ron J. G.,
Meijers Joost C. M.,
Büller Harry R.,
Levi Marcel
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2003.04811.x
Subject(s) - recombinant factor viia , partial thromboplastin time , medicine , pharmacology , prothrombin time , anesthesia , anticoagulant , heparin , placebo , coagulation , chemistry , alternative medicine , pathology
Summary We investigated whether the anticoagulant effect of idraparinux, a selective long‐acting factor Xa inhibitor, could be neutralized by recombinant factor VIIa (rFVIIa) in healthy male volunteers. We performed a randomized, placebo‐controlled trial, comparing idraparinux [7·5 mg subcutaneous (s.c.)] followed at 3 h by rFVIIa [90 μ g/kg intravenous (i.v.)] ( n = 6), or idraparinux (7·5 mg s.c) followed after 1 week by rFVIIa (90 μ g/kg i.v.)( n = 6). rFVIIa, given 3 h after idraparinux, significantly reversed the increased thrombin generation time (TGT), the increased activated partial thromboplastin time (aPTT) and prothrombin time (PT), and the reduced prothrombin fragment 1+2 (F 1+2 ) levels caused by idraparinux, although no clear effect of rFVIIa on the endogenous thrombin potential (ETP) was observed. One week after idraparinux, injection of rFVIIa resulted in a similar relative reduction of the remaining increased aPTT, PT and TGT, with correction to pre‐idraparinux values. A clear increase of F 1+2 was observed, together with a small increase in ETP. We conclude that rFVIIa has significant effects on the idraparinux‐inhibited thrombin generation and clotting parameters. These results suggest that rFVIIa may be useful in serious bleeding complications in idraparinux treated patients.