title: Biorheology of platelet activation in the bloodstream distal to thrombus formation.
abstract: Thrombus growth at the site of vascular injury is mediated by the sequential events of platelet recruitment, activation and aggregation concomitant with the initiation of the coagulation cascade, resulting in local thrombin generation and fibrin formation. While the biorheology of a localized thrombus formation has been well studied, it is unclear whether local sites of thrombin generation propagate platelet activation within the bloodstream. In order to study the physical biology of platelet activation downstream of sites of thrombus formation, we developed a platform to measure platelet activation and microaggregate formation in the bloodstream. Our results show that thrombi formed on collagen and tissue factor promote activation and aggregation of platelets in the bloodstream in a convection-dependent manner. Pharmacological inhibition of the coagulation factors (F) X, XI or thrombin dramatically reduced the degree of distal platelet activation and microaggregate formation in the bloodstream without affecting the degree of local platelet deposition and aggregation on a surface of immobilized collagen. Herein we describe the development and an example of the utility of a platform to study platelet activation and microaggregate formation in the bloodstream (convection-limited regime) relative to the local site of thrombus formation.
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR, USA.
authors.forename: Jevgenia
authors.initials: J
authors.lastname: Zilberman-Rudenko
authors.affiliation: Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, USA; Drug Discovery, Bayer Pharma AG, Wuppertal, Germany.
authors.forename: Asako
authors.initials: A
authors.lastname: Itakura
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR, USA; Chemical and Biomedical Engineering, West Virginia University, Morgantown, WV.
authors.forename: Jeevan
authors.initials: J
authors.lastname: Maddala
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR, USA.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Baker-Groberg
authors.affiliation: Drug Discovery, Bayer Pharma AG, Wuppertal, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Vetter
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR, USA; Division of Hematology / Medical Oncology, School of Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Erik I
authors.initials: EI
authors.lastname: Tucker
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR, USA; Division of Hematology / Medical Oncology, School of Medicine, Oregon Health & Science University, Portland, OR, USA; Aronora Inc., Portland, OR, USA.
authors.forename: András
authors.initials: A
authors.lastname: Gruber
authors.affiliation: Drug Discovery, Bayer Pharma AG, Wuppertal, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Gerdes
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR, USA; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, USA; Division of Hematology / Medical Oncology, School of Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Owen J T
authors.initials: OJ
authors.lastname: McCarty
keywords: biophysics; factor X; factor XI; physical biology; platelets; shear; thrombin