title: Platelet aggregation in laminar flow. II. Shear rate and ADP-dependent effects of acetylsalicylic acid and indomethacin.
abstract: The relative contributions of physiologic activators and shear rates (G) on the formation and stability of platelet aggregates arising from platelets treated with widely clinically used non-steroidal anti-inflammatory drugs such as acetylsalicylic acid (ASA) need to be characterized for conditions of low G believed to be important in vivo. In Part I of these studies it was found that platelets in human citrated platelet-rich plasma (PRP) undergo ADP-induced aggregation in laminar flow by apparently two distinct processes: a low ADP-dependent process, generating large visible aggregates stably only at low shear rates, and a higher ADP-threshold-dependent process yielding more complete and shear-resistant large aggregate formation. Similar studies of both macroaggregation (TA) and actual % aggregation (%PA) were made with ADP injections into PRP in the cone-in-plate device as a function of G and pre-treatments with ASA (200 microM) and indomethacin (10 microM). These drugs reduced %PA in part and yielded only reversible macro-aggregation for studies conducted at the higher [ADP] (4-6 microM) and at high G (greater than or approximately 120-150 sec-1), with no significant effects at low G (less than or approximately 20 sec-1). The results are discussed in terms of a platelet stickiness factor 's', ascribed to changes in fibrinogen binding sites reported for these drug actions, and related to in vivo flow and variable platelet activation conditions.
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D004780:Environment, Controlled; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D009391:Nephelometry and Turbidimetry; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000244:Adenosine Diphosphate; D001241:Aspirin; D007213:Indomethacin