title: Effect of ketorolac and low-molecular-weight heparin individually and in combination on haemostasis.
abstract: Low-molecular-weight heparins, when used in surgical patients for thromboprophylaxis, may be used concurrently with ketorolac, a non-steroidal anti-inflammatory drug that is used for analgesia. Because these two agents can influence the haemostatic system, it is important to identify any such effect. The haemostatic interaction between dalteparin and ketorolac was assessed in a double-blind, placebo-controlled, randomized, crossover study of healthy male volunteers each given all four combinations of ketorolac/placebo and dalteparin/placebo. The effect of ketorolac and dalteparin on haemostasis was assessed by measuring in-vitro platelet aggregation, anti-factor-Xa, activated partial thromboplastin times and skin bleeding time. The results were analysed for evidence of an interaction between ketorolac and dalteparin. Ketorolac inhibited platelet aggregation in whole blood and platelet-rich plasma. The administration of dalteparin led to a significant increase in levels of anti-factor-Xa and a significant prolongation in the activated partial thromboplastin time, although it remained within the range of the normal population. There was no evidence of any interaction between ketorolac and dalteparin with regard to platelet aggregation, anti-factor-Xa activity or activated partial thromboplastin time. The administration of ketorolac significantly prolonged the skin bleeding time. There was a significant interaction between ketorolac and dalteparin to prolong the bleeding time, although dalteparin alone had no effect on bleeding time. There was an interaction between ketorolac and dalteparin, which affected bleeding times. Such an interaction raises the possibility of haemorrhagic complications developing perioperatively when these agents are used concomitantly. Further studies are required to examine the clinical importance of this interaction.
authors.affiliation: Department of Obstetrics & Gynaecology, University of Glasgow, Glasgow Royal Infirmary, Scotland, UK. GQTA03@udcf.gla.ac.uk
authors.forename: I A
authors.initials: IA
authors.lastname: Greer
authors.forename: J L
authors.initials: JL
authors.lastname: Gibson
authors.forename: A
authors.initials: A
authors.lastname: Young
authors.forename: J
authors.initials: J
authors.lastname: Johnstone
authors.forename: I D
authors.initials: ID
authors.lastname: Walker
mesh_terms: D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001760:Bleeding Time; D017985:Dalteparin / Q000494:pharmacology; D065427:Factor Xa Inhibitors; D006487:Hemostasis / Q000187:drug effects*; D006493:Heparin; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D020910:Ketorolac / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin; D017985:Dalteparin; D020910:Ketorolac