Dataset Information

Effects of immunosuppressive agents on the hemostatic system in normal dogs.

ABSTRACT:

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-F_1? (6-keto-PGF_1? ) 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?1? -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.

SUBMITTER: Thomason JM

PROVIDER: S-EPMC6060322 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of immunosuppressive agents on the hemostatic system in normal dogs.

Thomason John M JM Archer Todd M TM Wills Robert W RW Mackin Andrew J AJ

Journal of veterinary internal medicine 20180510 4

<h4>Background</h4>In dogs, the effects of immunosuppressive medications on hemostasis are not well known.<h4>Hypothesis/objectives</h4>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.<h4>Animals</h4>Eight healt ...[more]

PMID: 29749651

Similar Datasets

Project description:BACKGROUND:Dogs are often adminstered >1 immunosuppressive medication when treating immune-mediated diseases, and determining whether these different medications affect IL-2 expression would be useful when performing pharmacodynamic monitoring during cyclosporine therapy. HYPOTHESIS/OBJECTIVES:To determine the effects of 5 medications (prednisone, cyclosporine, azathioprine, mycophenolate mofetil, and leflunomide) on activated T-cell expression of the cytokines IL-2 and interferon-gamma (IFN-?). ANIMALS:Eight healthy dogs. METHODS:Randomized, cross-over study comparing values before and after treatment, and comparing values after treatment among drugs. Dogs were administered each drug at standard oral doses for 1?week, with a washout of at least 21?days. Activated T-cell expression of IL-2 and IFN-? mRNA was measured by quantitative reverse transcription polymerase chain reaction. Blood drug concentrations were measured for cyclosporine, mycophenolate, and leflunomide metabolites. RESULTS:Least squares means (with 95% confidence interval) before treatment for IL-2 (2.91 [2.32-3.50] ?Ct) and IFN-? (2.33 [1.66-3.00 ?Ct]) values were significantly lower (both P?<?.001) than values after treatment (10.75 [10.16-11.34] and 10.79 [10.11-11.46] ?Ct, respectively) with cyclosporine. Similarly, least squares means before treatment for IL-2 (1.55 [1.07-2.02] ?Ct) and IFN-? (2.62 [2.32-2.92] ?Ct) values were significantly lower (both P?<?.001) than values after treatment (3.55 [3.06-4.00] and 5.22 [4.92-5.52] ?Ct, respectively) with prednisone. Comparing delta cycle threshold values after treatment among drugs, cyclosporine was significantly different than prednisone (IL-2 and IFN-? both P?<?.001), with cyclosporine more suppressive than prednisone. CONCLUSIONS AND CLINICAL IMPORTANCE:Prednisone and cyclosporine both affected expression of IL-2 and IFN-?, suggesting that both have the ability to influence results when utilizing pharmacodynamic monitoring of cyclosporine treatment.

Dataset Information

Effects of immunosuppressive agents on the hemostatic system in normal dogs.

Background

Hypothesis/objectives

Animals

Methods

Results

Conclusions and clinical importance

Publications

Effects of immunosuppressive agents on the hemostatic system in normal dogs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets