Evaluation of recombinant factor VIIa, tranexamic acid and desmopressin to reduce prasugrel-related bleeding: A randomised, placebo-controlled study in a rabbit model

BACKGROUND Prasugrel is a thienopyridine that inhibits platelet aggregation more rapidly and effectively than clopidogrel, with an increased bleeding risk. OBJECTIVE The current study aimed to evaluate the efficacy of three nonspecific haemostatic drugs – recombinant activated factor VII (rFVIIa), tranexamic acid and desmopressin (DDAVP) – to limit blood loss after administration of prasugrel in a rabbit model of bleeding while also evaluating any prothrombotic effects. DESIGN Randomised, placebo-controlled study. SETTING Faculty of Medicine, University of Geneva, Switzerland, in 2013. ANIMALS Anaesthetised and artificially ventilated rabbits (n=56). INTERVENTIONS Animals were randomly allocated to one of five groups: control (placebo–placebo), prasugrel–placebo, rFVIIa (prasugrel–rFVIIa 150 μg kg−1), tranexamic acid (prasugrel–tranexamic acid 20 mg kg−1) or DDAVP (prasugrel–DDAVP 1 μg kg−1). Two hours after an oral prasugrel loading dose (4 mg kg−1), a stenosis and an injury were inflicted on the carotid artery to induce cyclic flow reductions (CFRs) due to thrombosis. Haemostatic drugs were administered during the ensuing observation period. MAIN OUTCOME MEASURES Standardised hepatosplenic sections were performed to evaluate the primary endpoint of blood loss, monitored for 15 min. Ear-immersion bleeding time and incidence of CFRs were secondary endpoints. RESULTS Prasugrel decreased ADP-induced platelet aggregation (light transmission method) from 66 ± 4% (mean ± SD) to 41 ± 7% (P 

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