Combination of FVIII and by-passing agent potentiates in vitro thrombin production in hemophilia A inhibitor plasma
Résumé
By-passing agents, rVIIa (recombinant factor VII) and APCC (activated prothrombin complex concentrates), are important tools in the treatment of patients with haemophilia A and high-responding inhibitory antibodies. It has been observed clinically that in some patients undergoing immune tolerance induction the bleeding frequency decreases, hypothetically caused by a transient haemostatic effect of infused FVIII not measurable ex vivo. We evaluated how by-passing agents and factor VIII affect thrombin generation (TG) in vitro using plasma from 11 patients with severe haemophilia A and high titer of inhibitors. Samples were spiked with combinations of APCC, rFVIIa and five different factor VIII products. Combination of APCC and factor VIII showed for four factor VIII products a synergistic effect in eliciting TG (p<0.005). When rFVIIa and factor VIII were combined the interaction between the preparations was found to be additive. Further on, we combined APCC and rFVIIa without factor VIII, resulting in an additive effect on the thrombin production. Each product separately increased TG above baseline. In conclusion, the amount of thrombin formed in vitro by adding a by-passing agent, were higher in the presence of factor VIII. Our findings support the use of factor VIII in by-passing therapy to optimize the haemostatic effect.
Fichier principal
PEER_stage2_10.1111%2Fj.1365-2141.2010.08378.x.pdf (204.27 Ko)
Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...