Haemostatic effects of ketorolac with and without concomitant heparin in normal volunteers.
Ketorolac is a potent cyclo-oxygenase inhibitor used for the treatment of postoperative pain. It is known to have anti-platelet properties. The aim of this study was to determine the effect of ketorolac on haemostasis both alone and in combination with low dose heparin in 12 healthy male volunteers. Each volunteer received the following drug combinations in a double blind, placebo controlled, cross over manner: ketorolac placebo/heparin placebo, ketorolac active/heparin placebo, ketorolac active/heparin active and ketorolac placebo/heparin active. Ketorolac significantly prolonged bleeding time, inhibited platelet aggregation to arachidonic acid and collagen and platelet thromboxane production. Heparin had no effect on bleeding time or platelet function, but significantly prolonged the kaolin cephalin clotting time and increased anti-Xa levels. Ketorolac had no effect on the kaolin cephalin clotting time or anti-Xa levels and no interaction was found between ketorolac and heparin in any of the investigations. The prolongation of bleeding time seen with ketorolac is unlikely, to be of any major clinical significance as almost all subjects remained within the normal range; however, it should be used with caution in subjects with haemostatic problems.
Spowart
K
K
University Department of Obstetrics, Centre for Reproductive Biology, Edinburgh, UK.
Greer
I A
IA
McLaren
M
M
Lloyd
J
J
Bullingham
R E
RE
Forbes
C D
CD
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology; D001760:Bleeding Time; D004359:Drug Therapy, Combination; D015951:Factor Xa; D006490:Hemostatics; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D020910:Ketorolac; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors; D013929:Thromboxane B2 / Q000097:blood; D014046:Tolmetin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D006490:Hemostatics; D011758:Pyrroles; D015842:Serine Proteinase Inhibitors; D013929:Thromboxane B2; D006493:Heparin; D014046:Tolmetin; D015951:Factor Xa; D020910:Ketorolac