title: The effects of cyclosporine on platelet function and cyclooxygenase expression in normal dogs.
abstract: BACKGROUND
  Cyclosporine has been shown to alter platelet plasma membranes and have a hypercoagulable effect in humans, leading to thromboembolic complications.
  
  
  OBJECTIVE
  Our hypothesis was that by modulating platelet reactivity, cyclosporine increases the risk of thromboembolic complications. The objective was to determine the effects of cyclosporine on primary hemostasis in normal dogs.
  
  
  METHODS
  Eight healthy, intact female dogs.
  
  
  METHODS
  A repeated-measures design utilized flow cytometry to evaluate platelet expression of platelet reactivity markers (P-selectin and phosphatidylserine) and COX-1 and COX-2 during the administration of 2 cyclosporine dosages (19 mg/kg q12h [immunosuppressive dosage] and 5 mg/kg q24h [atopy dosage]). Urine 11-dehydro-thromboxane-B(2) (11-dTXB(2) ) concentration was normalized to urine creatinine concentration, and platelet function was analyzed by PFA-100.
  
  
  RESULTS
  After a week of the immunosuppressive dosage, all platelet reactivity markers showed a significant decrease in mean fluorescent intensity (MFI). After the atopy dosage, only P-selectin and COX-2 MFI demonstrated a change from baseline, decreasing by 29% (P = .013) and 31% (P = .003), respectively. Urinary 11-dTXB(2) -to-creatinine ratio significantly increased at all time points during the immunosuppressive dosage, but no significant change occurred during administration of the atopy dosage. PFA-100 closure times using collagen/ADP cartridges increased by 62% (P = .008) with the immunosuppressive dosage and decreased by 45% with the atopy dosage (P = .035). No significant changes in closure times occurred with collagen/epinephrine cartridges.
  
  
  CONCLUSIONS
  Our study suggests that, similar to what is observed in humans, cyclosporine alters the platelet plasma membrane and increases thromboxane production in dogs, especially at immunosuppressive dosages.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762-6100, USA. thomason@cvm.msstate.edu
authors.forename: J
authors.initials: J
authors.lastname: Thomason
authors.forename: K
authors.initials: K
authors.lastname: Lunsford
authors.forename: J
authors.initials: J
authors.lastname: Stokes
authors.forename: L
authors.initials: L
authors.lastname: Pinchuk
authors.forename: R
authors.initials: R
authors.lastname: Wills
authors.forename: C
authors.initials: C
authors.lastname: Langston
authors.forename: S
authors.initials: S
authors.lastname: Pruett
authors.forename: A
authors.initials: A
authors.lastname: Mackin
mesh_terms: D000818:Animals; D015415:Biomarkers; D001792:Blood Platelets / Q000187:drug effects*; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019007:P-Selectin / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D013931:Thromboxanes / Q000378:metabolism / Q000652:urine
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D019007:P-Selectin; D010718:Phosphatidylserines; D013931:Thromboxanes; D016572:Cyclosporine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2