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 nonsteroidal 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 stable 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 μM) and indomethacin (10 μM). These drugs reduced %PA in part and yielded only reversible macro-aggregation for studies conducted at the higher [ADP] (4–6 μM) and at high G (≳ 120–150 sec −1), with no significant effects at low G (≲ 30 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.