Dual effects of diclofenac on human platelet adhesion in vitro

The effect of two non-steroidal anti-inflammatory drugs on the adhesion function of human platelets was evaluated Platelets isolated from healthy human subjects were treated for 10 min with the indicated dugs and then incubated in fibrinogen-coated microwell plates in the absence or in the presence of ADP (10 mu M) and thrombin (0.05 U/ml). After Ih of incubation, adherent platelets were measured using an enzymatic assay. ADP- and thrombin-stimulated adhesion was significantly inhibited by high doses (>500 mu M) of didofenac, while doses ranging from 50 to 300 mu M stimulated adhesion in the absence of agonists (resting platelets). A similar stimulatory effect on platelet adhesion was observed also with 20-500 mu M flurbiprofen. Moreover, immunocytofluorimetry demonstrated that diclofenac dose-dependently (10-500 mu M) induced the expression of GMP-140 and increased the expression of GPIIb/IIIa on the membrane of unstimulated platelets. High doses (> 500 mu M) of this drug inhibited thrombin-stimulated expression of GPIIb/IIIa and GMP-140.