The effects of varying doses of aspirin on human platelet activation induced by PAF, collagen and arachidonic acid.

Abstract

1. The effect of increasing doses of orally administered aspirin (30‐ 900 mg) on platelet aggregation and ATP release induced by arachidonic acid (AA), collagen and platelet activating factor (PAF) was assessed in 12 normal volunteers. 2. Aspirin ingestion was associated with a significant increase in EC50 for AA (P less than 0.0001) and collagen (P less than 0.0001) but not for PAF (P greater than 0.495) although the normal biphasic aggregation response for the latter was abolished. Maximum ATP release was reduced by aspirin for all three agonists. 3. The mean maximum degrees of inhibition of platelet aggregation induced by aspirin for AA, collagen and PAF were 100%, 48% and 21% of baseline, respectively. The corresponding mean maximum inhibition of ATP release was 100%, 63% and 57%. The minimum cumulative doses of aspirin producing these effects were 240, 240 and 90 mg for AA, collagen and PAF respectively. For collagen alone, there was a significant decrease in the degree of inhibition of aggregation between the last dose on day 1 (150 mg) and the baseline measurement on day 2. 4. Platelets from female subjects were more sensitive to collagen (P less than 0.05) and AA (P less than 0.01) stimulation compared with males. However, prior to aspirin ingestion, PAF produced a greater maximum response in platelets from females (P less than 0.02) while following aspirin ingestion PAF‐induced activation was inhibited to a greater degree in females (P less than 0.02). 5. These results indicate that collagen‐ and PAF‐induced platelet activation are only partially dependent on cyclo‐oxygenase and for PAF this seems related only to the second phase of aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)

Glycoprotein IIb/IIIa inhibition attenuates platelet-activating factor-induced platelet activation by reducing protein kinase C activity

“…TXA 2 receptor antagonism did not influence PAF‐induced platelet P‐selectin expression in the present study, whilst TXA 2 synthesis blockade by aspirin has previously been shown to inhibit PAF‐induced platelet aggregation [25]. Our results suggest that PAF‐induced platelet TXA 2 synthesis may be limited in unstirred hirudinized blood, as both physiological calcium levels and the lack of cell–cell contact may limit platelet TXA 2 synthesis [26].…”

Aspirin has limited ability to modulate shear-mediated platelet activation associated with elevated shear stress of ventricular assist devices

“…Several research groups have begun evaluating the effect of ASA in combination with other drugs (8, 12, 13, 44–49). Nonetheless, the effectiveness of such combined therapeutic approaches after exposure to defined dynamic shear stress profiles has been poorly studied and defined.…”

Effect of synthetic peptides corresponding to residues 313–332 of the αIIb subunit on platelet activation and fibrinogen binding to αIIbβ3

“…ATP secretion was determined in parallel to platelet aggregation in aliquots of 0.45 mL PRP along with 50 µL of luciferin/luciferase (to measure ATP secretion, Chrono‐lume reagent, Chronolog, Corp.), in a platelet aggregometer (model 560, Chronolog Corp.) at 37 °C, with continuous stirring at 1200 r.p.m. [18].…”