Propofol has both enhancing and suppressing effects on human platelet aggregation in vitro

Background: Volatile anesthetics are known to suppress platelet aggregation. In contrast, there is conflicting information regarding the effect of propofol on platelet function. The present study was designed to clarify the effects of propofol on platelet function and the mechanisms underlying these effects. Methods: Propofol or an equivalent volume of 10% Intralipos (as a control) was added to test tubes 5 min before the induction of each reaction. Platelet aggregation induced by epinephrine, arachidonic acid (AA), prostaglandin G(2) (PGG(2)), or STA(2) (a thromboxane A(2) [TXA(2)] analog) was measured using an eight-channel aggregometer. To determine type 1 cyclooxygenase activity, AA (0.5 mM) was added to an assay mixture containing type 1 cyclooxygenase, and the concentration of the final product, malonaldehyde, was measured by spectrophotometry. Epinephrine-, adenosine diphosphate-, AA-, and PGG(2)-induced TXA(2) formation was measured using a commercially available radioimmunoassay kit. To estimate TXA(2) receptor-binding affinity, H-3-S145, a specific TXA(2) receptor antagonist, was added, and the radioactivity of receptor-bound H-3-S145 was determined using a liquid scintillation analyzer. Inositol 1,4,5-triphosphate formation was measured in STA(2)-stimulated platelets using a commercially available inositol 1,4,5-triphosphate assay kit. Results: Propofol (40 mu M) enhanced, whereas 100 mu M suppressed, adenosine diphosphate- and epinephrine-induced secondary aggregation without affecting primary aggregation. Propofol (40 mu M) also enhanced, but 100 mu M suppressed, AA-induced aggregation. Propofol (100 mu M) enhanced PGG(2)- and STA(2)-induced aggregation. Propofol (100 mu M) suppressed AA-induced TXA(2) formation but did not alter that induced by PGG(2). Propofol (30-100 mu M) suppressed AA- induced malonaldehyde formation, indicating inhibition of type 1 cyclooxygenase activity. Propofol did not alter TXA(2) receptor-binding affinity. Propofol (50 and 100 mu M) augmented inositol 1,4,5-triphosphate formation in STA(2)-stimulated platelets. Conclusions: The present findings clearly indicate that high concentrations of propofol suppress the activity of type 1 cyclooxygenase, the enzyme that converts AA to PGG(2). Furthermore, propofol also enhanced STA(2)-induced inositol 1,4,5-triphosphate formation. These results may explain the inconsistent findings of previous investigators.