title: Platelet thrombus formation on collagen type I. A model of deep vessel injury. Influence of blood rheology, von Willebrand factor, and blood coagulation.
abstract: Collagen type I is a major component of atherosclerotic vessel wall that is exposed on deep vessel injury, such as in balloon angioplasty or plaque rupture. Collagen type I from pig Achilles tendon was mounted in a tubular perfusion chamber placed within an extracorporeal circuit (carotid artery to jugular vein). The material was exposed to blood from normal pigs (n = 13), severe homozygous von Willebrand factor (vWF)-deficient pigs (vWF less than 3%) (n = 6), and heterozygous vWF-deficient pigs (vWF = 24%) (n = 2). Thrombus formation was measured by autologous 111In-platelet labeling and by ultrastructural morphology. Heparinized and native blood from these pigs was perfused over the substrate for 3 and 5 minutes at local shear rates from 212 to 3,380/sec. On collagen type I exposed to nonanticoagulated blood, for all exposure times studied, thrombus formation in the absence of vWF was significantly reduced at high shear rate typical of stenotic areas but not at low shear rate typical of unobstructed medium-size arteries. A similar inhibition in thrombus formation due to vWF deficiency was observed in both heparinized and native blood; however, thrombus formation was significantly more reduced (p less than 0.05) in the presence of heparin, presumably due to the lack of stability of the accumulated platelets in the absence of fibrin formation. Intermediate levels of vWF, as in heterozygous von Willebrand's disease (vWD), support platelet deposition to extents not significantly different from normal conditions. Therefore, on collagen type I, both the activation of blood coagulation proteins and the presence of vWF contribute significantly to the platelet-platelet interactions necessary for thrombus formation. The effect of vWF occurs primarily at high shear conditions typical intravascularly of flow at the apex of advanced stenotic lesions; thus, these findings may suggest that the absence of vWF may be protective against the development of acute thrombosis in these regions.
authors.affiliation: Division of Cardiology, Mount Sinai Medical Center, New York, NY 10029.
authors.forename: L
authors.initials: L
authors.lastname: Badimon
authors.forename: J J
authors.initials: JJ
authors.lastname: Badimon
authors.forename: V T
authors.initials: VT
authors.lastname: Turitto
authors.forename: S
authors.initials: S
authors.lastname: Vallabhajosula
authors.forename: V
authors.initials: V
authors.lastname: Fuster
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D003094:Collagen / Q000145:classification; D006493:Heparin / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D010974:Platelet Aggregation / Q000187:drug effects; D012039:Regional Blood Flow; D012212:Rheology; D013314:Stress, Mechanical; D013552:Swine; D013927:Thrombosis / Q000209:etiology*; D013997:Time Factors; D014652:Vascular Diseases / Q000150:complications* / Q000503:physiopathology; D014841:von Willebrand Factor / Q000502:physiology*
chemical_list: D014841:von Willebrand Factor; D006493:Heparin; D003094:Collagen