Platelet size distribution measurements as indicators of shear stress-induced platelet aggregation

• Published in: Annals of biomedical engineering Vol. 22; no. 6; p. 653
• Main Authors: Slack, S M, Jennings, L K, Turitto, V T
• Format: Journal Article
• Language: English
• Published: United States 01.11.1994
• Subjects: Antibodies, Monoclonal; Blood Platelets - cytology; Blood Platelets - metabolism; Cell Size; Glycoproteins - metabolism; Humans; Integrins - metabolism; Platelet Aggregation; Platelet Glycoprotein GPIIb-IIIa Complex; Receptors, Cytoadhesin - metabolism; Receptors, Vitronectin; Rheology; Stress, Mechanical; Vitronectin; von Willebrand Factor - metabolism
• ISSN: 0090-6964; 1573-9686
• DOI: 10.1007/BF02368290

The mechanisms underlying shear stress-induced platelet aggregation (SIPA) were investigated by measuring changes in the platelet size distributions resulting from the exposure of human platelet-rich plasma (PRP) to well-defined shear stresses in a modified viscometer. Exposure of PRP to a shear stress of 100 dyne/cm2 for 1 min at 37 degrees C resulted in the loss of single platelets, an overall shift in the distribution to larger particle sizes, and the generation of platelet fragments. Treatment of PRP prior to shearing with a monoclonal antibody directed against platelet glycoprotein (GP) IIb-IIIa (integrin alpha IIb beta 3) at a concentration that completely inhibited ADP-induced platelet aggregation also inhibited SIPA. Furthermore, incubation of PRP with a recombinant fragment of von Willebrand factor (vWF) that abolishes ristocetin-induced platelet agglutination significantly inhibited but did not eliminate SIPA. Pretreatment of PRP with the tetrapeptides RGDS or RGDV, which constitute the GP IIb-IIIa peptide recognition sequences on fibrinogen and vWF, almost completely blocked platelet aggregation at 100 dyne/cm2, whereas the negative control peptide RGES had no discernible effect. Finally, incubation of PRP with a monoclonal antibody directed against the platelet vitronectin receptor (integrin alpha v beta 3) did not affect SIPA. These results indicate that both GP IIb-IIIa and GP Ib, the latter through its interaction with vWF, are required for SIPA at 100 dyne/cm2; that the interaction of GP IIb-IIIa with its adhesive ligands under shear stress can be inhibited by RGD-containing peptides; and that the vitronectin receptor on platelets, which shares the same beta 3 subunit as GP IIb-IIIa, plays no role in SIPA.