The Effects of Cyclosporine and Aspirin on Platelet Function in Normal Dogs

J Vet Intern Med. 2016 Jul;30(4):1022-30. doi: 10.1111/jvim.13960. Epub 2016 May 7.

Abstract

Background: Cyclosporine increases thromboxane synthesis in dogs, potentially increasing the thrombogenic properties of platelets.

Hypothesis/objectives: Our hypothesis was that the concurrent administration of low-dose aspirin and cyclosporine would inhibit cyclosporine-associated thromboxane synthesis without altering the antiplatelet effects of aspirin. The objective was to determine the effects of cyclosporine and aspirin on primary hemostasis.

Animals: Seven healthy dogs.

Methods: A randomized, crossover study utilized turbidimetric aggregometry and a platelet function analyzer to evaluate platelet function during the administration of low-dose aspirin (1 mg/kg PO q24h), high-dose aspirin (10 mg/kg PO q12h), cyclosporine (10 mg/kg PO q12h), and combined low-dose aspirin and cyclosporine. The urine 11-dehydro-thromboxane-B2 (11-dTXB2 )-to-creatinine ratio also was determined.

Results: On days 3 and 7 of administration, there was no difference in the aggregometry amplitude or the platelet function analyzer closure time between the low-dose aspirin group and the combined low-dose aspirin and cyclosporine group. On day 7, there was a significant difference in amplitude and closure time between the cyclosporine group and the combined low-dose aspirin and cyclosporine group. High-dose aspirin consistently inhibited platelet function. On both days, there was a significant difference in the urinary 11-dTXB2 -to-creatinine ratio between the cyclosporine group and the combined low-dose aspirin and cyclosporine group. There was no difference in the urinary 11-dTXB2 -to-creatinine ratio among the low-dose aspirin, high-dose aspirin, and combined low-dose aspirin and cyclosporine groups.

Conclusions and clinical importance: Low-dose aspirin inhibits cyclosporine-induced thromboxane synthesis, and concurrent use of these medications does not alter the antiplatelet effects of aspirin.

Keywords: Canine; Immune-mediated hemolytic anemia; Immunosuppression; Thromboxane.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Animals
  • Aspirin / administration & dosage
  • Aspirin / pharmacology*
  • Blood Platelets / drug effects*
  • Cross-Over Studies
  • Cyclosporine / pharmacology*
  • Dogs / blood*
  • Immunosuppressive Agents / pharmacology
  • Nephelometry and Turbidimetry
  • Platelet Aggregation
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacology

Substances

  • Immunosuppressive Agents
  • Platelet Aggregation Inhibitors
  • Cyclosporine
  • Aspirin