Platelet dysfunction after intravenous ketorolac or propacetamol

Background: Paracetamol is a weak cyclo-oxygenase inhibitor in vitro. A rec ent study in children has shown that high doses of paracetamol are effectiv e and safe. We studied the effect of propacetamol on haemostasis in adult v olunteers. Methods: Ten volunteers were investigated in a double-blind, randomized, cr ossover study. They received propacetamol 60 mg kg(-1) or ketorolac 0.4 mg kg(-1) in saline i.v. (30 min) in two different sessions. Platelet function was evaluated before the test infusion (S-0), two (S-2) and 24 h (S-24) af ter the start of the infusion. Coagulation parameters (PT, APTT, factor V a nd VII activities) were measured at S-0, S-24 and 48 h (S-48). Results: One of the volunteers had no secondary platelet aggregation in S-0 and was excluded from the final analysis. Two hours (S-2) after propacetam ol and ketorolac administration the adrenaline (0.9 mu g ml(-1) and 9.0 mu g ml(-1)) induced maximal platelet aggregation was decreased compared with S-0. At S-2 platelet aggregation was inhibited more after ketorolac than af ter propacetamol. At 24 h after ketorolac, but not after propacetamol, ther e was still a decrease in the adrenaline-induced maximal platelet aggregati on. Propacetamol did not affect adenosine di-phosphate (ADP)-induced maxima l platelet aggregation, whereas ketorolac decreased 3 and 6 mu M ADP-induce d maximal platelet aggregation at S-2 and S-24. However, 2 h after both ket orolac and propacetamol, thromboxane B-2 (TXB2) concentration decreased in platelet rich plasma after 5 min aggregation induced by 8 mu M ADP. Coagula tion was unaffected. Conclusion: Propacetamol 60 mg kg(-1) i.v. causes reversible platelet dysfu nction demonstrated by a decrease in maximal platelet aggregation and TxB(2 ) concentration. After 0.4 mg kg(-1) ketorolac i.v. platelet aggregation an d TxB(2) formation are inhibited more in comparison with propacetamol, and platelet dysfunction is still seen after 24 h.