Shear and elongational flows and relation to platelet plug formation and thrombosis. (A) Shear flow, which may be represented as elongational flow superimposed on rotational flow.^40,41  Arrows show streamlines and dots regions of no flow. (B) Cartoon of VWF elongating, compressing, and tumbling in shear flow.⁴³  (C) Stills representing the last frame of movies simulating VWF in shear and elongational flows at the indicated rates (supplemental Videos 1-6). VWF is represented as a string of 50 spheres (cyan except for spheres at the 2 ends in magenta). Simulations are similar to those described in Schneider et al³⁵  and Sing and Alexander-Katz.⁴⁴  Simulations and movies are courtesy of Darren Yang and Wesley Wong (Children’s Hospital, Boston, MA). Both shear and elongational flows are measured as velocity/distance and have units of s⁻¹. VWF becomes thread-like at much lower values of elongational flow than shear flow. (D-E) Shear and elongational flows in a bleeding vessel (D) and stenotic vessel (E). Round orange spheres show the effect of elongational flow on the shape of a polymeric protein in the flow field.⁴⁴  Two zones of elongational flow marked 1 and 2 are described in “The shape of VWF” section. Elongation of VWF concatemers would occur in the directions shown by the orange globules. (F) Light micrographs of rat mesentery artery (top) and vein (bottom) before and 9 minutes after the wall of the vein was nicked with scissors. Reprinted from Zucker⁹⁶  with permission. A platelet plug (arrow) lies above the vein. Vasoconstriction occurs in both the artery and vein and is only seen when a platelet plug is formed, demonstrating that platelet plugs release a diffusible vasoconstrictor.⁹⁶  (G-I) Human skin wound experiment for determination of bleeding time. Reprinted from Wester et al⁹⁵  with permission. (G) Schematic showing the morphology of the hemostatic plug (HP) formed by a transected vessel (Vs). The plug is 90% outside the vessel. (H-I) Biopsy excised 30 seconds after wounding. Two light micrographs a few sections apart are shown of the same hemostatic plug (HP) formed at the outflow of a transected vessel. D, dermis; E, epidermis; Vs, transected vessel; W, wound. (J-K) Differential interference contrast microscopy of thrombosis formation at sites of vessel constriction in vivo (J) and in vitro (K), reprinted from Nesbitt et al¹⁰⁰  with permission. Flow is left to right. Scale bars are 10 μm. (J) Mouse mesenteric arteriole crush injured with a needle. A platelet aggregate (cyan shading) forms downstream of the injury and stenosis site (red arrow). Blue and yellow arrows mark the center and downstream extent of the platelet aggregate. Time is shown in seconds. After release of the stenosis the aggregate embolized (24 seconds). (K) Whole blood in a microchannel with a 90% stenosis and downstream expansion. Red and black arrows mark the margins of the platelet aggregate (cyan shading). Much less aggregation was noticed with a lower rate of downstream expansion; that is, with lower elongational flow rates.¹⁰⁰