Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin.
Fluid shear stress in arteries and arterioles partially obstructed by atherosclerosis or spasm may exceed the normal time-average level of 20 dyne/cm2. In vitro, at fluid shear stresses of 30 to 60 dyne/cm2 applied for 30 seconds, platelet aggregation occurs. At these shear stresses, either large or unusually large von Willebrand factor (vWF) multimers in the suspending fluid exogenous to the platelets mediates aggregation. Adenosine diphosphate (ADP) is also required and, in these experiments, was released from the platelets subjected to shear stress. At 120 dyne/cm2, the release of endogenous platelet vWF multimers can substitute for exogenous large or unusually large vWF forms in mediating aggregation. Endogenous released platelet vWF forms, as well as exogenous large or unusually large vWF multimers, must bind to both glycoproteins Ib and the IIb/IIIa complex to produce aggregation. Shear-induced aggregation is the result of shear stress alteration of platelet surfaces, rather than of shear effects on vWF multimers. It is mediated by either large plasma-type vWF multimers, endogenous released platelet vWF forms, or unusually large vWF multimers derived from endothelial cells, requires ADP, and is not inhibited significantly by aspirin. This type of aggregation may be important in platelet thrombus formation within narrowed arterial vessels, and may explain the limited therapeutic utility of aspirin in arterial thrombosis.
Moake
J L
JL
Biomedical Engineering Laboratory, Rice University, Houston, TX 77251.
Turner
N A
NA
Stathopoulos
N A
NA
Nolasco
L
L
Hellums
J D
JD
D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000378:metabolism / Q000502:physiology*
D014841:von Willebrand Factor; D000244:Adenosine Diphosphate; D001241:Aspirin