C LINICAL BLEEDING or thrombosis results from a disturbance in the balance between a complex network of procoagulant and anticoagulant factors. This network involves three primary interactions, first described by the eminent pathologist Rudolph Virchow during the previous century, between blood (soluble and cellular constituents), the blood vessel (including fixed and dynamic responses), and blood flow. This review examines one increasingly recognized feature of this interplay that appears to affect both hemostasis and thrombosis. This feature is the effect on blood platelets of the mechanical forces of shear generated by flowing blood. Knowledge of the link between platelets and shear stress provides clues to general mechanisms governing physiologic and pathologic processes by re-emphasizing the importance of physical forces in regulating cellular function in vivo.

Platelets have long been regarded as the preeminent cell involved in physiologic hemostasis and pathologic thrombosis. In both cases, the plasma protein von Willebrand factor (vWF) and the blood platelet work together to effect the biologic response. The versatility in biologic responses mediated by a single receptor-ligand coupling has been, and remains, one of the challenging conundrums placed before clinical investigators and practicing hematologists. It is all the more intriguing when one considers that mixing vWF with platelets in a static or stirred suspension evokes no response. The discovery that the mechanism of toxicity of the antibiotic ristocetin is its capacity to induce plasma vWF to bind to platelet glycoprotein (GP) Ib’stimulated numerous important discoveries about the structure and function of vWF and its platelet receptors, including the nosology of von Willebrand (vWD) disease.’-4 However, elucidation of mechanisms of hemostasis and thrombosis in vivo required the convergence of classical pathology with modem molecular biology. One hundred and forty years after it was proposed, Rudolf Virchow’s concept of the pathogenesis of thrombosis holds the key to understanding the relationship between platelets and shear stress. Virchow’s triad is a concept that is old but does not recidivate; rather, it confronts observations and their interpretation within a context of the interrelated pathophysiologic elements of blood, blood vessel, and blood flow. It is the application of Virchow’s principles to the puzzle of vWF-mediated platelet aggregation that ultimately led to the discovery