PMID: 8977459Dec 1, 1996Paper

Ultrastructural studies of platelet aggregates from human subjects receiving clopidogrel and from a patient with an inherited defect of an ADP-dependent pathway of platelet activation

Arteriosclerosis, Thrombosis, and Vascular Biology
M HumbertA Nurden

Abstract

Our study investigated the effect of the antithrombotic drug clopidogrel (75 mg/d for 7 days) on the ultrastructure of platelet aggregates induced by ADP or 2-methylthio-ADP (2-MeS-ADP) in citrated platelet-rich plasma and examined the activation state of the GP IIb/IIIa complexes. Results were compared with those obtained for patient M.L., who has a congenital disorder characterized by a reduced and reversible platelet response to ADP. When untreated normal platelets were stimulated with high-dose ADP, electron microscopy revealed large and stable aggregates often surrounded by a layer of what appeared to be degranulated platelets. The reversible aggregates of platelets from subjects receiving clopidogrel or from patient M.L. did not show this layer. Electron microscopy showed that in both situations, the aggregates were composed of loosely bound platelets with few contact points. Immunogold labeling of ultrathin sections of Lowicryl-embedded aggregates formed by ADP or 2-MeS-ADP showed a much decreased platelet surface staining by (1) a polyclonal anti-fibrinogen antibody and (2) AP-6, a murine anti-ligand-induced binding site monoclonal antibody specific for GP IIb/IIIa complexes occupied with fibrinogen. Similar findings we...Continue Reading

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Citations

Jul 28, 2011·Purinergic Signalling·Béatrice Hechler, Christian Gachet
Oct 12, 2012·International Journal of Hematology·Fatemeh Moheimani, Denise E Jackson
Jul 16, 2011·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Samuel Yip, Oscar Benavente
Jun 16, 2005·Pharmacology & Therapeutics·Christian Gachet
Jan 30, 2003·The Journal of Emergency Medicine·Charles V Pollack
Dec 3, 2005·The Journal of Clinical Investigation·Lawrence F BrassTimothy J Stalker
Dec 3, 2005·The Journal of Clinical Investigation·Lawrence F Brass
Aug 8, 2015·Thrombosis and Haemostasis·Mohammed MakkawiDenise E Jackson
Feb 14, 2006·Blood Cells, Molecules & Diseases·Lawrence F BrassLi Zhu
Jun 24, 2006·Platelets·P SaviJ M Herbert
Feb 18, 2003·British Journal of Haematology·Jean O ContreresSylviane Levy-Toledano
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·A K Rao
Oct 23, 2010·Pharmacology & Therapeutics·Hong-Guang XieShao-Liang Chen

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