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Titolo:
Disaggregation of in vitro preformed platelet-rich clots by abciximab increases fibrin exposure and promotes fibrinolysis
Autore:
Collett, JP; Montalescot, G; Lesty, C; Soria, J; Mishal, Z; Thoms, D; Soria, C;
Indirizzi:
Pitie Salpetriere Hosp, Dept Cardiol, Paris, France Pitie Salpetriere Hosp Paris France e Hosp, Dept Cardiol, Paris, France Pitie Salpetriere Hosp, Hematol Res Ctr, Paris, France Pitie Salpetriere Hosp Paris France osp, Hematol Res Ctr, Paris, France Hotel Dieu Hosp, Res Lab St Marie, Paris, France Hotel Dieu Hosp Paris France Dieu Hosp, Res Lab St Marie, Paris, France Paul Brousse Hosp, CNRS, UPS 937, Villejuif, France Paul Brousse Hosp Villejuif France sp, CNRS, UPS 937, Villejuif, France Lariboisiere Hosp, Hemostasis Lab, Paris, France Lariboisiere Hosp ParisFrance iere Hosp, Hemostasis Lab, Paris, France
Titolo Testata:
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
fascicolo: 1, volume: 21, anno: 2001,
pagine: 142 - 148
SICI:
1079-5642(200101)21:1<142:DOIVPP>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLASMINOGEN-ACTIVATOR INHIBITOR-1; MEDIATED FORCE DEVELOPMENT; GLYCOPROTEIN-IIB/IIIA; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; THROMBOLYSIS; BIOPOLYMERS; RESISTANCE; RETRACTION; NETWORKS;
Keywords:
platelets; fibrin; fibrinolysis; glycoprotein IIb/IIIa inhibitors;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Collett, JP Ctr Hosp Univ Pitie Salpetriere, Dept Cardiol, 47 Blvd Hop, F-75013 Paris,France Ctr Hosp Univ Pitie Salpetriere 47 Blvd Hop Paris France F-75013
Citazione:
J.P. Collett et al., "Disaggregation of in vitro preformed platelet-rich clots by abciximab increases fibrin exposure and promotes fibrinolysis", ART THROM V, 21(1), 2001, pp. 142-148

Abstract

The glycoprotein IIb/IIIa receptor inhibitor abciximab has been shown to facilitate the rate and the extent of pharmacological thrombolysis with recombinant tissue plasminogen activator (rtPA) in patients with acute myocardial infarction, However, the underlying mechanisms remain not fully determined. We sought to demonstrate that this facilitating effect of abciximab could be related to its potential to modify the clot architecture and the clotphysical properties. Compared with fibrin-rich clots, platelets dramatically modified the in vitro properties of the fibrin network, leading to a significant increase of the permeability (K-s) and the viscoelasticity (G') indexes but also leading to the appearance of platelet aggregates (surface area [S,ag]). These modifications resulted in a 2.6-fold decrease of the fibrinolysis rate when rtPA (1 nmol/L) was added before the initiation of clotting. Adding aspirin (100 mug/mL) or abciximab (0.068 mu mol/L) before the clotting of platelet-rich clots (PRCs) lowered K-s by 50% and 70%, respectively (P<0.01), G' by 41% and 66%, respectively (P<0.01), and S.ag by 32% and61%, respectively (P<0.01), As a consequence, the lysis speed was increased by 21% with aspirin (P<0.01) and 45% with abciximab (P<0.01), However, unlike aspirin, permeation of preformed PRCs with abciximab (0.068 <mu>mol/L)decreased G' (37%, P<0.01), K-s (35%, P<0.001) and S.ag (25%, P=NS) and resulted in a 27% (P<0.01) increase of the lysis speed when abciximab and rtPA (0.2 <mu>mol/L) were simultaneously permeated. This effect was found to be time dependent and was observed only with early permeation, starting within the first 10 minutes of clotting. These changes in the physical properties of the PRC architecture suggest that fibrin is removed from the platelet-fibrin aggregates and reexposed into the surrounding fibrin network, increasing rtPA access to fibrin and therefore the fibrinolysis rate. The superiority of abciximab over aspirin in accelerating fibrinolysis of forming andpreformed PRCs is related to its ability to modulate the interactions of fibrinogen and fibrin with platelets. These findings provide new mechanisticinformation on reperfusion therapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 10:21:43