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Effects of immunosuppressive agents on the hemostatic system in normal dogs
Ist Teil von
Journal of veterinary internal medicine, 2018-07, Vol.32 (4), p.1325-1333
Ort / Verlag
United States: John Wiley and Sons Inc
Erscheinungsjahr
2018
Quelle
MEDLINE
Beschreibungen/Notizen
Background
In dogs, the effects of immunosuppressive medications on hemostasis are not well known.
Hypothesis/Objectives
The objective was to determine the effects of immunosuppressive medications on primary and secondary hemostasis. Our hypothesis was that cyclosporine and prednisone would increase markers of hypercoagulability and thromboxane synthesis, while azathioprine, mycophenolate mofetil, and leflunomide would have minimal effects on hemostasis.
Animals
Eight healthy dogs.
Methods
A randomized, cross‐over study used aggregometry, the PFA‐100 platelet function analyzer, viscoelastometry, platelet count, and prothrombin and activated partial thromboplastin times to evaluate hemostasis during the administration of prednisone, azathioprine, cyclosporine, mycophenolate mofetil, and leflunomide for 1 week each at standard oral doses. Urine 11‐dehydro‐thromboxane‐B2 (11‐dTXB2) and 6‐keto‐prostaglandin‐F1α (6‐keto‐PGF1α) concentrations, normalized to urine creatinine concentration, were measured.
Results
The aggregometry amplitude decreased from 51 ± 21 to 27 ± 14 (P = .002) during leflunomide treatment (ADP activation), but there were no differences in amplitude (P = .240) for any medications when platelets were activated with collagen. For all medications, there were no significant differences in viscoelastometry indices (ACT, P = .666; ClotRate, P = .340; and platelet function, P = .411) and platelet count (P = .552). Compared with pretreatment values, urinary 11‐dTXB2‐to‐creatinine ratio increased (P = .001) after drug administration (from 3.7 ± 0.6 to 5.6 ± 1.1). Cyclosporine was associated with an increase (P < .001) in the 6‐keto‐PGF1α‐to‐creatinine ratio (from 10.3 ± 4.6 to 22.1 ± 5.3).
Conclusions and Clinical Importance
Most immunosuppressive drugs do not enhance platelet function or coagulation in healthy dogs, suggesting that these medications might not predispose hypercoagulable dogs to thromboembolism. The results of our study need to be correlated with the clinical outcomes of hypercoagulable dogs.