Document Detail


Dichotomous effects of exposure to bivalirudin in patients undergoing percutaneous coronary intervention on protease-activated receptor-mediated platelet activation.
MedLine Citation:
PMID:  23054462     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bivalirudin is a direct thrombin inhibitor that is increasingly used in percutaneous coronary intervention (PCI) and has been previously shown to lack inherent platelet activation. Thrombin works through activation of protease activated receptor-1 (PAR1) and PAR4 on human platelets to initiate signaling cascades leading to platelet aggregation. Despite the increasing usage of bivalirudin, the effects on platelet function have not been well defined. Bivalirudin exposure during PCI was therefore assessed for its potential short-term effects on washed platelet function through PAR1 and PAR4. Bivalirudin significantly inhibited low-dose thrombin-mediated platelet aggregation, dense granule secretion, integrin αIIbβ3 activation and Rap1 activation and high dose thrombin-mediated dense granule secretion and Rap1 activation. Exposure to bivalirudin did not alter PAR1 or 4 agonist peptide (PAR1-AP or PAR4-AP) induced aggregation, dense granule secretion, integrin glycoprotein IIbIIIa activation or Rap1 activation. However, exposure to bivalirudin significantly potentiated surface expression of P-selectin following stimulation with high dose thrombin and PAR1-AP, and both low and high dose PAR4-AP. Hence, our data are the first to show that exposure to bivalirudin increased P-selectin expression with certain conditions demonstrating that bivalirudin can increase inherent platelet activity.
Authors:
Michael Holinstat; Nancy E Colowick; Willie J Hudson; Dana Blakemore; Qingxia Chen; Heidi E Hamm; John H Cleator
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of thrombosis and thrombolysis     Volume:  35     ISSN:  1573-742X     ISO Abbreviation:  J. Thromb. Thrombolysis     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  2013-10-17     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  9502018     Medline TA:  J Thromb Thrombolysis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  209-22     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aged
Antithrombins / adverse effects,  pharmacology*
Dose-Response Relationship, Drug
Female
Hirudins / adverse effects,  pharmacology*
Humans
Male
Middle Aged
P-Selectin / biosynthesis
Peptide Fragments / adverse effects,  pharmacology*
Percutaneous Coronary Intervention* / trends
Platelet Activation / drug effects*,  physiology
Receptor, PAR-1 / physiology*
Receptors, Thrombin / metabolism*
Recombinant Proteins / adverse effects,  pharmacology
Treatment Outcome
Grant Support
ID/Acronym/Agency:
P50-HL081009/HL/NHLBI NIH HHS; R00 HL089457/HL/NHLBI NIH HHS; R00-HL089457/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antithrombins; 0/Hirudins; 0/P-Selectin; 0/Peptide Fragments; 0/Receptor, PAR-1; 0/Receptors, Thrombin; 0/Recombinant Proteins; 0/protease-activated receptor 4; 128270-60-0/bivalirudin
Comments/Corrections

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


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