Effects of ketorolac and dextran-70 alone and in combination on haemostasis.
BACKGROUND
Dextran may be used in surgical patients for thromboprophylaxis or volume expansion along with ketorolac, a nonsteroidal anti-inflammatory drug, for analgesia. As these two agents can influence the haemostatic system at different sites, it is important to demonstrate that there is no adverse haemostatic interaction between them.


METHODS
The haemostatic interaction between intravenous dextran-70 and intramuscular ketorolac was assessed in a double-blind, randomised, crossover study of healthy male volunteers each given all four combinations of ketorolac/placebo intramuscularly and dextran/placebo intravenously. The effect of ketorolac and dextran on haemostasis was assessed by the following techniques: skin bleeding time, in vitro platelet aggregation function, whole blood thromboxane generation, von Willebrand factor antigen, factor VIII coagulant activity and tissue plasminogen activator. The results were analysed for the effects of ketorolac and dextran and for any evidence of an interaction.


RESULTS
Ketorolac inhibited platelet function and thromboxane generation. Dextran reduced factor VIII coagulant activity. Neither agent had a significant effect on bleeding time, von Willebrand factor or tissue plasminogen activator. There was only evidence of a small but statistically significant interaction between ketorolac and dextran on thromboxane generation. There was no evidence of any other interaction of ketorolac with dextran.


CONCLUSIONS
This interaction on thromboxane generation is unlikely to be of clinical significance as substantial inhibition of thromboxane generation occurs with ketorolac alone.
Department of Anaesthesia and Pain Management, University of Sydney, St Leonards, New South Wales, Australia.
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Power
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Noble
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Winter
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Greer
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001760:Bleeding Time; D018592:Cross-Over Studies; D003911:Dextrans / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D006487:Hemostasis / Q000187:drug effects*; D006490:Hemostatics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007267:Injections; D020910:Ketorolac; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood; D014046:Tolmetin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003911:Dextrans; D006490:Hemostatics; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D014046:Tolmetin; D020910:Ketorolac