Red blood cells may have a physical and chemical effect on the interaction between platelets and blood vessel surfaces. Under flow conditions in which primarily physical effects prevail, platelet adhesion increases fivefold as hematocrit values increase from 10 to 40 percent but undergoes no further increase from 40 to 70 percent, implying a saturation of the transport-enhancing capabilities of red cells. For flow conditions in which platelet-surface reactivity is more dominant, platelet adhesion and thrombus formation increase monotonically as hematocrit values increase from 10 to 70 percent. Thus red cells may have a significant influence on hemostasis and thrombosis; the nature of the effect is apparently related to the flow conditions.

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The shear rate and corresponding shear stress have impacts on arterial thrombus formation. In particular, the effects of increasing concentration of platelets at the vessel wall and activation of platelets at this site increase the growth and stability of the thrombi which may result in a fatal narrowing of the arterial lumen. The efficacy of many antithrombotic agents is shear dependent as well. It is apparent that there is a need for a point-of-care device to rapidly monitor the risk for arterial thrombosis and to optimize antithrombotic therapy in vitro. The present review focuses on the essential role of shear rate on arterial thrombus formation in native human blood drawn directly from an antecubital vein.

Platelet adhesion and thrombus formation on subendothelium, studied at a shear rate of 2,600 s'l, were inhibited by two synthetic peptides known to interact with GPIIb-IIIa. One peptide (HHLGGAKQAGDV) corresponds to the carboxyl terminal segment of the fibrinogen y-chain ('y400411) and the other (RGDS) contains the amino acid sequence Arg-Gly-Asp (RGD) common to fibronectin, von Willebrand factor, vitronectin and the a-chain of fibrinogen. Neither platelet adhesion nor thrombus formation were decreased in a patient with severe congenital fibrinogen deficiency and this was equally true when his blood was further depleted of the small amounts of fibrinogen present utilizing an anti-fibrinogen antibody. In normal subjects, adhesion and thrombus formation were inhibited by the Fab' fragments of a monoclonal anti-GPIIb-IIIa antibody (LJ-CP8), which interferes with the interaction of platelets with all four adhesive proteins in both the fluid and solid phase. However, another anti-GPIIb-IIIa antibody (LJ-PS) that had minimal effects on the interaction of platelets with fibrinogen, but inhibited to varying degrees platelet interaction with other adhesive proteins, was equally effective. The findings demonstrate that, at a shear rate of 2,600 s5, adhesive proteins other than fibrinogen are involved in GPIIb-IIIa-mediated platelet adhesion and thrombus formation on subendothelium. In addition, since LJ-P5 inhibited the binding of soluble von Willebrand factor and vitronectin, these adhesive proteins may be involved in platelet thrombus formation. In contrast to the results obtained at a shear rate of 2,600 s51, fibrinogen could play a role in mediating platelet-platelet interactions with weak agonists or lower shear rates.

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