Axial dependence of platelet-collagen interactions in flowing blood. Upstream thrombus growth impairs downstream platelet adhesion.
Vascular subendothelium and collagenous surfaces were exposed to flowing citrated blood. Platelet interactions with these surfaces were investigated at various axial distances from the upstream end of the exposed surfaces. A pronounced axial decrease in surface coverage with platelets and in thrombus dimensions was encountered on collagenous surfaces. This phenomenon was observed at shear rates of 200 to 2000 s-1, but was most pronounced at low shear rates (less than 650 s-1). After 5 minutes of perfusion at a shear rate of 650 s-1, 4.6 x 10(6) platelets were deposited on the most upstream 20 mm2 of the collagen surface, in contrast to 2.2 x 10(6) platelets/20 mm2 14 mm farther downstream. Depletion of von Willebrand factor and/or thrombospondin from the boundary layer of the blood flow was not responsible for this. Collagen-bound von Willebrand factor enhanced the surface coverage with platelets without affecting the axial decrement, while pretreatment of the collagen surface with thrombospondin had no effect at all. However, partial inhibition of thrombus growth by aspirin reduced the axial decrements, and less thrombogenic surfaces as human and rabbit subendothelium, which induced only a few small thrombi, produced virtually no axial differences in platelet adhesion. Raising the shear rate to 2600 s-1 also gave no axial differences in platelet-collagen adhesion; it did, however, give an axial increase in thrombus dimensions. This increase was neutralized after the addition of antibody against human platelet thrombospondin to the blood.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmaceutical Research, F. Hoffmann-La Roche & Company, Basel, Switzerland.
K S
KS
Sakariassen
H R
HR
Baumgartner
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001777:Blood Coagulation; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002860:Chromium Radioisotopes; D003094:Collagen / Q000097:blood*; D004730:Endothelium, Vascular / Q000502:physiology; D006023:Glycoproteins / Q000276:immunology / Q000502:physiology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007700:Kinetics; D010973:Platelet Adhesiveness; D011817:Rabbits; D013499:Surface Properties; D019699:Thrombospondins; D014841:von Willebrand Factor / Q000502:physiology
D002860:Chromium Radioisotopes; D006023:Glycoproteins; D007106:Immune Sera; D019699:Thrombospondins; D014841:von Willebrand Factor; D003094:Collagen; D001241:Aspirin