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Titolo:
Ability of recombinant factor VIIa to generate thrombin during inhibition of tissue factor in human subjects
Autore:
Friederich, PW; Levi, M; Bauer, KA; Vlasuk, GP; Rote, WE; Breederveld, D; Keller, T; Spataro, M; Barzegar, S; Buller, HR;
Indirizzi:
Univ Amsterdam, Acad Med Ctr, Dept Vasc Med & Internal Med F4, NL-1105 AZ Amsterdam, Netherlands Univ Amsterdam Amsterdam Netherlands NL-1105 AZ Z Amsterdam, Netherlands Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA USA Harvard Univ Boston MA USA ed, Boston VA Healthcare Syst, Boston, MA USA Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA Harvard Univ Boston MA USA Beth Israel Deaconess Med Ctr, Boston, MA USA Corvas Int Inc, San Diego, CA USA Corvas Int Inc San Diego CA USACorvas Int Inc, San Diego, CA USA
Titolo Testata:
CIRCULATION
fascicolo: 21, volume: 103, anno: 2001,
pagine: 2555 - 2559
SICI:
0009-7322(20010529)103:21<2555:AORFVT>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
FACTOR PATHWAY INHIBITOR; ACTIVATED FACTOR-VII; HUMAN ATHEROSCLEROTIC PLAQUES; FACTOR-IX; FACTOR-X; BLOOD-COAGULATION; PROTEIN-C; MECHANISM; HEMOPHILIA; PATIENT;
Keywords:
anticoagulants; coagulation; thrombosis; drugs; inhibitors;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Levi, M Univ Amsterdam, Acad Med Ctr, Dept Vasc Med & Internal Med F4, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands Univ Amsterdam Meibergdreef 9 Amsterdam Netherlands NL-1105 AZ ds
Citazione:
P.W. Friederich et al., "Ability of recombinant factor VIIa to generate thrombin during inhibition of tissue factor in human subjects", CIRCULATION, 103(21), 2001, pp. 2555-2559

Abstract

Background-In view of the central role of the tissue factor-factor VIIa pathway in the initiation of blood coagulation, novel therapeutic strategies aimed at inhibiting this catalytic complex are currently being evaluated. Alimitation of this new class of anticoagulants may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs. The aim of this study was to investigate the in vivo potential of recombinant factorVIIa (rVIIa) to induce thrombin generation in healthy subjects pretreated with recombinant nematode anticoagulant protein c2, a specific inhibitor ofthe tissue factor-factor VIIa complex, in a double-blind randomized crossover study. Methods and Results-Administration of nematode anticoagulant protein c2 (3.5 mug/kg) caused a prolongation of the prothrombin time from 13.7+/-0.6 to16.9+/-1.2 seconds. The subsequent injection of rVIIa (90 mug/kg) resultedin an immediate and complete correction of the prothrombin time and a marked generation of thrombin, reflected by increased levels of prothrombin activation fragment F1+2 and thrombin-antithrombin complexes from 0.75+/-0.64 to 3.29+/-6.3 nmol/L and from 2.4+/-0.6 to 10.7+/-3.9 mug/mL, respectively. Factor X and IX activation peptides showed a 3.5-fold and a 3.8-fold increase, respectively, after the administration of rVIIa in the presence of nematode anticoagulant protein c2. Conclusions-During treatment with an inhibitor of the tissue factor-factorVIIa complex, the infusion of rVIIa resulted in thrombin generation. Our results indicate that rVIIa may be a good candidate as an antidote for inhibitors of tissue factor.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 23:22:43