title: Fibrinolytic agents inhibit platelet adhesion onto collagen type I-coated surfaces at high blood flow conditions.
abstract: The effect of fibrinolytic agents on platelet adhesion onto insolubilized collagen type I was evaluated. Normal human whole blood samples were incubated with agents and perfused over collagen-coated surfaces in a parallel-plate flow chamber. Platelet adhesion and aggregation were analyzed by video microscopy and image processing. When blood was perfused at 1500/s, both streptokinase and urokinase, each at 500 U/ml, caused a significantly less normalized platelet deposition, compared with controls. At 480/s, platelet deposition was not different between controls and test samples. Inhibition of platelet deposition at high flow rates was partly due to inhibition of platelet adhesion. Both ristocetin- and ADP-induced platelet aggregation were inhibited in test samples. The agents caused proteolytic degradation of plasma fibrinogen, but no degradation of platelet glycoproteins Ib and IIb-IIIa (GPIb and GPIIb-IIIa) and of plasma von Willebrand factor in test samples prior to perfusion. Post-perfusion von Willebrand factor degradation was not found. Plasmin may cause functional changes to plasma proteins and/or platelet receptors, altering their adhesive properties under flow. At high shear, fibrinogen degradation products may interfere with GPIIb-IIIa binding to insolubilized von Willebrand factor, leading to decreased platelet adhesion. Inhibition of platelet adhesion by thrombolytic agents could help maintain vessel patency after recanalization in stenosed arteries. Publishers.
authors.affiliation: Biomedical Engineering Department, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Huang
authors.forename: D A
authors.initials: DA
authors.lastname: Graham
authors.forename: L D
authors.initials: LD
authors.lastname: Nelson
authors.forename: B R
authors.initials: BR
authors.lastname: Alevriadou
mesh_terms: D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D003094:Collagen / Q000378:metabolism*; D003864:Depression, Chemical; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D018056:Hemorheology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D018715:Microscopy, Video; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D012310:Ristocetin / Q000037:antagonists & inhibitors; D013300:Streptokinase / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; D012310:Ristocetin; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D003094:Collagen; D013300:Streptokinase; D014568:Urokinase-Type Plasminogen Activator