Interaction of low molecular weight heparin with ketorolac.
Postoperative patients may receive ketorolac, a nonsteroidal antiinflammatory drug that inhibits platelet function, for analgesia and may receive low-molecular-weight heparin (LMWH) for thrombosis prevention. We investigated whether the combination of these two agents increases blood loss in a rabbit model of hemostasis. In a randomized, blinded study, animals received either intramuscular ketorolac (0.5 mg/kg or 1.0 mg/kg) and subcutaneous saline solution, subcutaneous LMWH (100 U/kg) and intramuscular saline solution, ketorolac (0.5 mg/kg or 1.0 mg/kg) and subcutaneous LMWH (100 U/kg), or intramuscular and subcutaneous saline solution given 30 minutes before ear incision and measurement of blood loss. Collagen-induced platelet aggregation was examined and anti-Xa levels were determined by using a chromogenic substrate method. As compared with results in saline-treated controls, blood loss was significantly increased in animals receiving ketorolac in a dose of 1.0 mg/kg but not in those treated with 0.5 mg/kg. The addition of LMWH did not further increase blood loss above that observed with either dose of ketorolac alone. Platelet aggregation was inhibited by both doses of ketorolac. The anti-Xa levels in the LMWH-treated animals were comparable to those measured in patients receiving these agents for prophylaxis (0.09 to 0.13 U/ml). We conclude that in the rabbit model, LMWH does not augment ketorolac-associated bleeding when both agents are used in doses comparable to those given to human patients.
Green
D
D
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA.
Klement
P
P
Liao
P
P
Weitz
J
J
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D016063:Blood Loss, Surgical; D004347:Drug Interactions; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000009:adverse effects*; D020911:Ketorolac Tromethamine; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors; D011817:Rabbits; D011897:Random Allocation; D014046:Tolmetin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D014325:Tromethamine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D010975:Platelet Aggregation Inhibitors; D014325:Tromethamine; D020911:Ketorolac Tromethamine; D014046:Tolmetin