10339485

Source:http://linkedlifedata.com/resource/pubmed/id/10339485

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Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0023820, umls-concept:C0032173, umls-concept:C0600433, umls-concept:C1280500
pubmed:issue	11
pubmed:dateCreated	1999-6-24
pubmed:abstractText	Plasma and platelet factor Va represent different substrates for activated protein C (APC). In this study, we have measured platelet-dependent APC resistance and the effect of aspirin and a platelet glycoprotein IIbIIIa antagonist (GR144053F) on this phenomenon. In platelet rich plasma (PRP), progressive APC resistance was observed with increasing platelet activation. APC sensitivity ratios of 1.8, 1.7, and 1.4 were observed after platelet activation with thrombin receptor activating peptide (TRAP), collagen, and A23187, respectively. Ultracentrifugation at 77,000g for 1 hour abolished APC resistance indicating that the phenotype is associated exclusively with the platelet membrane. APC resistance was not observed in the presence of phosphatidylcholine-phosphatidylserine (PCPS) vesicles or purified human plasma lipoproteins. APC resistance was observed in the presence of platelet-derived microparticles, but to a lesser degree than that in the presence of activated platelets. The platelet-dependent APC resistance phenotype was also observed when endogenous APC was generated by Protac (American Diagnostica, Inc, Greenwich, CT). In vitro inhibition of platelet activation with aspirin had no effect, but the fibrinogen receptor antagonist, GR144053F, inhibited platelet-dependent APC resistance. These results indicate that platelet activation results in an APC-resistant phenotype comparable to that observed in the plasma of patients with factor V gene mutations affecting critical APC cleavage sites. This suggests that platelet activation at the site of endothelial damage downregulates a critical natural anticoagulant mechanism. The antithrombotic effect of aspirin may be due to an indirect effect on platelet-dependent APC resistance with reduced platelet retention within a developing thrombus. The more potent antithrombotic effect of glycoprotein IIbIIIa antagonists may in addition be the result of reduced platelet factor Va expression and modulation of the platelet-dependent APC resistance phenotype.
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/7603509
pubmed:citationSubset	AIM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins
pubmed:status	MEDLINE
pubmed:month	Jun
pubmed:issn	0006-4971
pubmed:author	pubmed-author:BaglinTT, pubmed-author:ByrneC DCD, pubmed-author:LuddingtonRR, pubmed-author:McWilliamNN, pubmed-author:TaubeJJ
pubmed:issnType	Print
pubmed:day	1
pubmed:volume	93
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	3792-7
pubmed:dateRevised	2006-11-15
pubmed:meshHeading	pubmed-meshheading:10339485-Activated Protein C Resistance, pubmed-meshheading:10339485-Cytoplasmic Granules, pubmed-meshheading:10339485-Humans, pubmed-meshheading:10339485-Lipoproteins, pubmed-meshheading:10339485-Platelet Activation
pubmed:year	1999
pubmed:articleTitle	Activated protein C resistance: effect of platelet activation, platelet-derived microparticles, and atherogenic lipoproteins.
pubmed:affiliation	Department of Haematology and the University Department of Clinical Biochemistry, Addenbrooke's NHS Trust, Cambridge, UK.
pubmed:publicationType	Journal Article, Research Support, Non-U.S. Gov't