A fluid shear stress of 180 dyn/cm2 was applied for 0.5 and 5 min to platelets in citrated plasma or blood in a cone and plate viscometer with minimal platelet-surface interactions. Platelets aggregated in the shear field if large von Willebrand Factor (vWF) multimers were present. Aggregation did not require ristocetin, other exogenous agents, or desialation of vWF. Unusually large vWF multimers produced by human endothelial cells were functionally more effective than the largest plasma vWF forms in supporting shear-induced aggregation. Shear-induced aggregation was inhibited by monoclonal antibodies to platelet glycoprotein Ib or the IIb/IIIa complex, but was little affected by the absence of fibrinogen. vWF-dependent platelet aggregation under elevated shear stress in partially occluded vessels of the arterial microcirculation may contribute to thrombosis, especially if unusually large vWF multimers are released locally from stimulated or disrupted endothelial cells.

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Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation.

ONE decade after the Food and Drug Administration approved the plasminogen activators streptokinase and urokinase, thrombolytic therapy is no longer a novel approach to the treatment of thrombotic ...

Thrombolytic therapy: current status (1).

Studies with a murine monoclonal antibody that abolishes ristocetin- induced binding of von Willebrand factor to platelets: additional evidence in support of GPIb as a platelet receptor for von Willebrand factor

The binding of 125I-von Willebrand factor (125I-vWF) to platelets stimulated by thrombin, ADP, and a combination of ADP + epinephrine (EPI) is specific, saturable, and reversible. Active platelet metabolism and divalent cations are required for binding induced by these stimuli, but not by ristocetin, suggesting the existence of different mechanisms involved in the vWF-platelet interaction. A monoclonal antibody directed against an epitope of membrane glycoprotein (GP) Ib had no effect on the binding of 125I-vWF to normal platelets stimulated by thrombin or a combination of ADP + EPI, but completely blocked ristocetin-induced binding. Binding induced by thrombin to GPIb-blocked platelets was specific. Moreover, thrombin-induced binding of 125I-vWF was increased, rather than decreased, in two patients with the Bernard-Soulier syndrome whose platelets lacked GPIb. Conversely, monoclonal antibodies directed against the GPIIb/IIIa complex had no effect on ristocetin-induced binding of 125I-v-WF to normal platelets, but blocked thrombin- and ADP + EPI-induced binding. To exclude effects mediated by the platelet Fc receptor, a monoclonal IgG directed against an epitope present on human B cells and monocytes, but not expressed on resting or stimulated platelets, was used. It did not affect 125I-vWF binding induced by any of the stimuli. These studies show that platelets have more than one binding site for vWF, and that they may be exposed by different stimuli.

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Platelets have more than one binding site for von Willebrand factor.

EARLY in this century, it was clearly demonstrated that blood platelets are essential for hemostasis,1 and shortly thereafter the first report appeared demonstrating that a congenital hemorrhagic disease can result from abnormal platelet function.2 Since that time, descriptions of many additional disorders have greatly added to our understanding of the role of platelets in normal hemostasis.3 4 5 6 Analytical techniques developed during the past decade have helped both to identify the molecular abnormalities causing these disorders and to define the mechanisms of platelet-vessel-wall interactions. It has been demonstrated that platelet function requires the presence of specific receptors on the platelet surface that . . .

T. Funicella

Papers

Binding of radioiodinated human von Willebrand factor to Bernard-Soulier, thrombasthenic and von Willebrand's disease platelets