title: Injection of recombinant activated factor VII can induce transient increase in circulating procoagulant microparticles.
abstract: Recombinant activated factor VII (rFVIIa) is an effective haemostatic treatment in haemophiliacs with inhibitors. In vitro, FVIIa concentrations corresponding to those obtained with therapeutic doses of rFVIIa have been shown to induce normal thrombin generation and platelet activation in the absence of factors VIII or IX. To further study the in vivo haemostatic changes induced by rFVIIa, circulating procoagulant microparticles (MP) were measured in patients treated with discontinuous injections of Novoseven. In 6 out of 15 patients, a transient peak of procoagulant MP was observed after injection, occurring 15 min to 2 h after infusion. It was composed primarily of platelet-derived MP and was of very short duration. This peak was not observed in haemophiliacs without inhibitor, who were treated with conventional replacement therapies. Our results provide further in vivo evidence that rFVIIa specifically activates platelets, either directly or as a consequence of a burst of thrombin generation that could account for its haemostatic efficacy.
authors.affiliation: INSERM Unit 143, Hôpital Bicêtre, Le Kremlin Bicêtre, France. proulle@kb.inserm.fr
authors.forename: Valérie
authors.initials: V
authors.lastname: Proulle
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Hugel
authors.forename: Benoit
authors.initials: B
authors.lastname: Guillet
authors.forename: Catherine
authors.initials: C
authors.lastname: Trichet
authors.forename: Anne
authors.initials: A
authors.lastname: Rafowicz
authors.forename: Thierry
authors.initials: T
authors.lastname: Lambert
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Freyssinet
authors.forename: Marie
authors.initials: M
authors.lastname: Dreyfus
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017304:Annexin A5; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D005167:Factor VII / Q000008:administration & dosage / Q000494:pharmacology*; D015942:Factor VIIa; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D019851:Thrombophilia / Q000139:chemically induced*
chemical_list: D017304:Annexin A5; D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa