Document Detail


An anti-von Willebrand factor aptamer reduces platelet adhesion among patients receiving aspirin and clopidogrel in an ex vivo shear-induced arterial thrombosis.
MedLine Citation:
PMID:  21078615     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The von Willebrand factor (vWF) aptamer, ARC1779 that blocks the binding of vWF A1-domain to platelet glycoprotein 1b (GPIb) at high shear, may deliver a site-specific antithrombotic effect. We investigated the efficiency of ARC1779 on platelet function in patients with coronary artery disease (CAD) on double antiplatelet therapy. Blood from patients taking aspirin and clopidogrel and from normal volunteers was treated ex vivo with ARC1779 or abciximab, either prior to perfusion (pretherapy) or 10 minutes following the initiation of perfusion (posttherapy) on damaged arteries. Under pre- but not posttherapy, platelet adhesion was significantly reduced by ARC1779 at 83 and 250 nmol/L and by abciximab (100 nmol/L) versus placebo (4.8, 3.8, and 2.9 vs 7.3 platelets × 10(6)/cm(2), P < .05). In contrast to abciximab, ARC1779 did not significantly affect platelet aggregation, P-selectin expression, and platelet-leukocyte binding. These proof-of-concept data may constitute the framework for randomized clinical investigations of this novel antiplatelet therapy among patients with CAD.
Authors:
Dabit Arzamendi; Firas Dandachli; Jean-François Théorêt; Gregory Ducrocq; Mark Chan; Walid Mourad; James C Gilbert; Robert G Schaub; Jean-François Tanguay; Yahye Merhi
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2010-11-15
Journal Detail:
Title:  Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis     Volume:  17     ISSN:  1938-2723     ISO Abbreviation:  Clin. Appl. Thromb. Hemost.     Publication Date:    2011 Nov-Dec
Date Detail:
Created Date:  2012-02-20     Completed Date:  2012-10-03     Revised Date:  2013-05-24    
Medline Journal Info:
Nlm Unique ID:  9508125     Medline TA:  Clin Appl Thromb Hemost     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E70-8     Citation Subset:  IM    
Affiliation:
Department of Medicine, Montreal Heart Institute, Université de Montréal, Montreal, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adult
Antibodies, Monoclonal / therapeutic use
Aptamers, Nucleotide / therapeutic use*
Aspirin / therapeutic use*
Coronary Artery Disease / blood,  drug therapy*
Female
Humans
Immunoglobulin Fab Fragments / therapeutic use
Male
Middle Aged
Platelet Activation / drug effects
Platelet Adhesiveness / drug effects*
Platelet Aggregation / drug effects
Platelet Aggregation Inhibitors / therapeutic use*
Thrombosis / blood,  drug therapy*
Ticlopidine / analogs & derivatives*,  therapeutic use
von Willebrand Factor / antagonists & inhibitors,  metabolism
Chemical
Reg. No./Substance:
0/ARC 1779; 0/Antibodies, Monoclonal; 0/Aptamers, Nucleotide; 0/Immunoglobulin Fab Fragments; 0/Platelet Aggregation Inhibitors; 0/von Willebrand Factor; 50-78-2/Aspirin; 55142-85-3/Ticlopidine; A74586SNO7/clopidogrel; X85G7936GV/abciximab

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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