Prohemorrhagic potential of dipyrone, ibuprofen, ketorolac, and aspirin: mechanisms associated with blood flow and erythrocyte deformability.
Dipyrone, ibuprofen, ketorolac, and aspirin were tested in a well-defined perfusion system (shear rates: 300/s, 800/s, and 1,800/s). Whole blood samples were treated with the drugs at analgesic doses and platelet interaction with damaged subendothelium was measured. All the drugs fully inhibited platelet cyclooxygenase, as assessed by classic aggregometry. Perfusion studies showed that there was a general tendency to reduce the percentage of large aggregates (thrombus; %T), to increase the percentage of adhered platelets (adhesion; %A), and to reduce the height of thrombi with respect to control. Aspirin significantly increased %A and reduced %T at all shear rates tested, whereas dipyrone had the same effect at 800/s, and ketorolac and ibuprofen at 1,800/s. In addition, aspirin significantly reduced erythrocyte deformability with respect to the other drugs. In conclusion, under our experimental conditions, aspirin showed the most remarkable effects on platelet function, closely followed by dipyrone. The effects of ketorolac were moderate, whereas ibuprofen had a minor impact on platelet function.
Bozzo
J
J
Department of Hemotherapy and Hemostasis, Hospital Clinic, Barcelona, Spain. escobar@medicina.ub.es
Escolar
G
G
Hernández
M R
MR
Galán
A M
AM
Ordinas
A
A
D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001012:Aorta, Abdominal / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology; D004177:Dipyrone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D004907:Erythrocyte Deformability / Q000187:drug effects*; D006474:Hemorrhagic Disorders / Q000139:chemically induced* / Q000503:physiopathology; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D020910:Ketorolac / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004177:Dipyrone; D001241:Aspirin; D007052:Ibuprofen; D020910:Ketorolac