title: Shear stress activation of platelet glycoprotein IIb/IIIa plus von Willebrand factor causes aggregation: filter blockage and the long bleeding time in von Willebrand's disease.
abstract: The article explores the finding that high shear alone applied to normal, native blood results in platelet aggregation. A filter with tortuous capillary-sized channels permits a study of the effect of shearing forces at different pressures. Native, heparinized, citrated and EDTA blood and platelet-rich plasma (PRP) were forced through the filter. Normal and von Willebrand's blood were studied, as were the effects of antibodies to platelet glycoproteins (GPr) and to von Willebrand's factor (vWf) and of "membrane-active" drugs. Normally, the filter blocked at 40 mmHg but not at 5 mmHg. Transmission electronmicroscopy of the filter at 40 mmHg showed blockage by platelet aggregates. Initially, the mean transit time through the filter was 8 milliseconds. Platelet retention in the filter occurred in two phases. From 0 to 3 seconds, only high-shear, vWf, and GPrIIb/IIIa were required. From 10 to 20 seconds, retention presumably involved these three attributes, but divalent cations were also essential. Only this phase was inhibited by some membrane-active drugs. ADP- and thrombin-induced aggregation requires GPrIIb/IIIaand fibrinogen. Shear-induced blocking of the filter by blood with a normal concentration of fibrinogen requires GPrIIb/IIIa and vWf. This indicates a different type of exposure of GPrIIb/IIIa. The long bleeding time in vW disease highlights the absolute requirement for vWf and emphasizes the difference in exposure of GPrIIb/IIIa induced by shear stress. Evidently, a process similar to that occurring in the filter is required in normal capillary hemostasis.
mesh_terms: D000906:Antibodies; D001760:Bleeding Time; D001792:Blood Platelets / Q000648:ultrastructure; D006801:Humans; D007700:Kinetics; D008854:Microscopy, Electron; D010974:Platelet Aggregation; D010979:Platelet Function Tests; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D013314:Stress, Mechanical; D013997:Time Factors; D014842:von Willebrand Diseases / Q000097:blood*; D014841:von Willebrand Factor / Q000502:physiology*
chemical_list: D000906:Antibodies; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor