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dc.contributor.authorFurman, Mark I.
dc.contributor.authorKrueger, Lori A.
dc.contributor.authorFrelinger, Andrew L. III
dc.contributor.authorBarnard, Marc R.
dc.contributor.authorMascelli, Mary Ann
dc.contributor.authorNakada, Marian T.
dc.contributor.authorMichelson, Alan D.
dc.date2022-08-11T08:10:10.000
dc.date.accessioned2022-08-23T16:58:20Z
dc.date.available2022-08-23T16:58:20Z
dc.date.issued2000-09-01
dc.date.submitted2012-04-25
dc.identifier.citationThromb Haemost. 2000 Sep;84(3):492-8.
dc.identifier.issn0340-6245 (Linking)
dc.identifier.pmid11019977
dc.identifier.urihttp://hdl.handle.net/20.500.14038/43345
dc.description.abstractIn addition to inhibition of platelet aggregation, GPIIb-IIIa antagonists may reduce thrombotic events via other mechanisms. In a novel whole blood flow cytometric system, we investigated the effects of GPIIb-IIIa antagonists, in the presence or absence of thrombin inhibitors, on platelet surface-bound factor V/Va and platelet surface phospholipids. Diluted venous blood was incubated with either buffer or a GPIIb-IIIa antagonist (abciximab, tirofiban, or eptifibatide). Some samples were pre-incubated with clinically relevant concentrations of unfractionated heparin (UFH), a low molecular weight heparin, a direct thrombin inhibitor, or buffer only. Platelets were then activated and labeled with mAb V237 (factor V/Va-specific) or annexin V (binds phosphatidylserine), fixed, and analyzed by flow cytometry. In the absence of thrombin inhibitors, GPIIb-IIIa antagonists (especially abciximab) significantly reduced agonist-induced platelet procoagulant activity, as determined by reduced binding of V237 and annexin V. At high pharmacologic concentrations, unfractionated heparin and enoxaparin, but not hirudin, further reduced factor V/Va binding to the surface of activated platelets in the presence of GPIIb-IIa antagonists. Agonist-induced platelet procoagulant activity was reduced in a patient with Glanzmann's thrombasthenia. We conclude that GPIIb-IIIa antagonists reduce platelet procoagulant activity in whole blood and heparin and enoxaparin augment this reduction. Fibrinogen binding to GPIIb-IIIa is important in the generation of platelet procoagulant activity.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11019977&dopt=Abstract">Link to article in PubMed</a>
dc.relation.urlhttp://www.schattauer.de/en/magazine/subject-areas/journals-a-z/thrombosis-and-haemostasis/contents/archive/issue/889/manuscript/2537.html
dc.subjectAntibodies, Monoclonal
dc.subjectBlood Platelets
dc.subjectCollagen
dc.subjectDose-Response Relationship, Drug
dc.subjectFactor V
dc.subjectFlow Cytometry
dc.subjectHumans
dc.subjectImmunoglobulin Fab Fragments
dc.subjectInfant, Newborn
dc.subjectMembrane Proteins
dc.subjectPeptides
dc.subjectPhosphatidylserines
dc.subjectPlatelet Glycoprotein GPIIb-IIIa Complex
dc.subjectProtein Binding
dc.subjectThrombasthenia
dc.subjectThrombin
dc.subjectTyrosine
dc.subjectHematology
dc.subjectOncology
dc.subjectPediatrics
dc.titleGPIIb-IIIa antagonist-induced reduction in platelet surface factor V/Va binding and phosphatidylserine expression in whole blood
dc.typeArticle
dc.source.journaltitleThrombosis and haemostasis
dc.source.volume84
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/peds_hematology/23
dc.identifier.contextkey2796510
html.description.abstract<p>In addition to inhibition of platelet aggregation, GPIIb-IIIa antagonists may reduce thrombotic events via other mechanisms. In a novel whole blood flow cytometric system, we investigated the effects of GPIIb-IIIa antagonists, in the presence or absence of thrombin inhibitors, on platelet surface-bound factor V/Va and platelet surface phospholipids. Diluted venous blood was incubated with either buffer or a GPIIb-IIIa antagonist (abciximab, tirofiban, or eptifibatide). Some samples were pre-incubated with clinically relevant concentrations of unfractionated heparin (UFH), a low molecular weight heparin, a direct thrombin inhibitor, or buffer only. Platelets were then activated and labeled with mAb V237 (factor V/Va-specific) or annexin V (binds phosphatidylserine), fixed, and analyzed by flow cytometry. In the absence of thrombin inhibitors, GPIIb-IIIa antagonists (especially abciximab) significantly reduced agonist-induced platelet procoagulant activity, as determined by reduced binding of V237 and annexin V. At high pharmacologic concentrations, unfractionated heparin and enoxaparin, but not hirudin, further reduced factor V/Va binding to the surface of activated platelets in the presence of GPIIb-IIa antagonists. Agonist-induced platelet procoagulant activity was reduced in a patient with Glanzmann's thrombasthenia. We conclude that GPIIb-IIIa antagonists reduce platelet procoagulant activity in whole blood and heparin and enoxaparin augment this reduction. Fibrinogen binding to GPIIb-IIIa is important in the generation of platelet procoagulant activity.</p>
dc.identifier.submissionpathpeds_hematology/23
dc.contributor.departmentDepartment of Pediatrics
dc.source.pages492-8


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