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Platelet dysfunction after intravenous ketorolac or propacetamol
T T Niemi1, J T Backman, M T Syrjälä
1Department of Anaesthesiology, Helsinki University Central Hospital, Finland.
Insights
Propacetamol (a paracetamol prodrug) reversibly impairs platelet function and thromboxane B2 production in adults. Ketorolac, a non-steroidal anti-inflammatory drug, demonstrated more potent and prolonged inhibition of platelet aggregation and thromboxane B2 formation.
Area of Science:
- Pharmacology
- Hematology
Background:
- Paracetamol is a weak cyclo-oxygenase inhibitor.
- High-dose paracetamol has shown efficacy and safety in pediatric studies.
- The hemostatic effects of propacetamol in adults were previously unexamined.
Purpose of the Study:
- To investigate the impact of propacetamol on hemostasis in adult volunteers.
- To compare the effects of propacetamol with ketorolac on platelet function and coagulation.
Main Methods:
- A double-blind, randomized, crossover study involving ten adult volunteers.
- Administration of intravenous propacetamol (60 mg kg(-1)) or ketorolac (0.4 mg kg(-1)).
- Evaluation of platelet aggregation and thromboxane B2 (TxB2) levels at various time points; coagulation parameters were also assessed.
Main Results:
- Both propacetamol and ketorolac decreased maximal platelet aggregation and TxB2 concentration.
- Ketorolac exhibited a more pronounced and sustained inhibition of platelet aggregation compared to propacetamol.
- Coagulation parameters remained unaffected by either drug.
Conclusions:
- Propacetamol administration results in reversible platelet dysfunction, evidenced by reduced maximal platelet aggregation and TxB2 levels.
- Ketorolac demonstrates a stronger inhibitory effect on platelet aggregation and TxB2 formation than propacetamol, with effects persisting for 24 hours.
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 microg ml(-1) and 9.0 microg 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 microM 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 microM 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.