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Exploratory study on the reversal of warfarin with rFVIIa in healthy subjects
Journal article   Open access   Peer reviewed

Exploratory study on the reversal of warfarin with rFVIIa in healthy subjects

Brett E. Skolnick, David R. Mathews, Naum M. Khutoryansky, Anthony E. Pusateri and Marcus E. Carr
Blood, v 116(5), pp 693-701
05 Aug 2010
PMID: 20385794
url
https://doi.org/10.1182/blood-2009-11-253492View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

Hematology Life Sciences & Biomedicine Science & Technology
The use of warfarin has a well-known bleeding risk. Recombinant activated factor VII (rFVIIa) is a non-plasma-derived, rapid-acting, and rapidly infused potential treatment. This randomized, single-center, placebo-controlled, double-blinded, dose-escalation, exploratory phase 1 trial assessed safety and effects of rFVIIa in reversing warfarin-induced changes in bleeding and coagulation parameters, using a punch biopsy-induced bleeding model in healthy subjects. The effects of warfarin (experiment 1) and rFVIIa (580 mu g/kg; experiment 2) were evaluated. Outcomes were bleeding duration, blood loss, coagulation parameters, and safety. Warfarin treatment significantly increased bleeding duration and blood loss from pretreatment (experiment 1, 12 subjects). However, these parameters after rFVIIa treatment were not significantly different from placebo (experiment 2, 85 subjects). Mean activated partial thromboplastin time, prothrombin time, and international normalized ratio were reduced from warfarin-elevated levels. rFVIIa (80 mu g/kg) significantly reversed warfarin effects on all thromboelastography parameters, compared with placebo (P < .05), and returned the thrombin generation speed to baseline. There were no thromboembolic or serious adverse events. In this exploratory trial, the reversal of warfarin effects was observed in the thromboelastography, thrombin generation, and clotting assays. However, this reversal did not translate to improvements in the bleeding model parameters evaluated in the punch biopsy model. Trial registration is exempt (phase 1). (Blood. 2010;116(5): 693-701)

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Hematology
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