title: Shear-induced platelet activation and platelet microparticle formation in native human blood.
abstract: Shear-induced platelet activation and platelet microparticle formation are triggered in native human blood by high arterial shear or by a sudden increase in shear as introduced by a stenosis with potential consequences for collagen-induced platelet thrombus formation. Blood was drawn from healthy volunteers and directly perfused ex vivo over various well-defined eccentric stenoses. Shear-induced platelet activation was determined by using flow cytometry to assess: 1) GPIIb-IIIa activation by fluorescein isothiocyanate (FITC)-labeled Mab PAC-1; and 2) translocation of membrane aminophospholipids (procoagulant activity) by FITC-labeled Annexin V. Microparticle formation was measured by flow cytometry and FITC-labeled Mab Y2/51 directed against GPIIIa. Significant platelet activation and platelet microparticle formation were elicited when the wall shear rate reached 10,500 sec-1 for a period of 0.075 sec. Prolonged exposure to or a rapid increase in shear further enhanced activation and microparticle formation. Shear-induced platelet activation was associated with significantly increased collagen-induced platelet thrombus formation that was insensitive to aspirin ingestion. Exposure of native blood to very high shear thus activates platelets to express GPIIb-IIIa, renders the platelet membrane procoagulant and stimulates microparticle formation. These responses are associated with enhanced collagen-induced thrombus formation by prostaglandin-independent mechanisms.
authors.affiliation: Bioreg Research, Nycomed Imaging AS, Oslo, Norway. kjell.sakariassen@eu.pnu.com
authors.forename: K S
authors.initials: KS
authors.lastname: Sakariassen
authors.forename: P A
authors.initials: PA
authors.lastname: Holme
authors.forename: U
authors.initials: U
authors.lastname: Orvim
authors.forename: R M
authors.initials: RM
authors.lastname: Barstad
authors.forename: N O
authors.initials: NO
authors.lastname: Solum
authors.forename: F R
authors.initials: FR
authors.lastname: Brosstad
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D008297:Male; D015539:Platelet Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000502:physiology; D013314:Stress, Mechanical
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex