Platelet dysfunction after intravenous ketorolac or propacetamol

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Abstract
Background: Paracetamol is a weak cyclo‐oxygenase inhibitor in vitro. A recent study in children has shown that high doses of paracetamol are effective and safe. We studied the effect of propacetamol on haemostasis in adult volunteers. Methods: Ten volunteers were investigated in a double‐blind, randomized, crossover 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) after the start of the infusion. Coagulation parameters (PT, APTT, factor V and 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 propacetamol and ketorolac administration the adrenaline (0.9 μg ml−1 and 9.0 μg ml−1) induced maximal platelet aggregation was decreased compared with S‐0. At S‐2 platelet aggregation was inhibited more after ketorolac than after propacetamol. At 24 h after ketorolac, but not after propacetamol, there was still a decrease in the adrenaline‐induced maximal platelet aggregation. Propacetamol did not affect adenosine diphosphate (ADP)‐induced maximal platelet aggregation, whereas ketorolac decreased 3 and 6 μM ADP‐induced maximal platelet aggregation at S‐2 and S‐24. However, 2 h after both ketorolac and propacetamol, thromboxane B2 (TxB2) concentration decreased in platelet rich plasma after 5 min aggregation induced by 8 μM ADP. Coagulation was unaffected. Conclusion: Propacetamol 60 mg kg−1 i.v. causes reversible platelet dysfunction demonstrated by a decrease in maximal platelet aggregation and TxB2 concentration. After 0.4 mg kg−1 ketorolac i.v. platelet aggregation and TxB2 formation are inhibited more in comparison with propacetamol, and platelet dysfunction is still seen after 24 h.