Effects of clopidogrel and prednisone on platelet function in healthy dogs

Abstract

Background: Glucocorticoids cause hypercoagulability, but it is unknown if they counteract clopidogrel's antiplatelet effects.Hypothesis/Objectives: Determine the effects of clopidogrel and prednisone on platelet function.Animals: Twenty-four healthy dogs.Methods: Double-blinded, placebo-controlled randomized trial. Platelet function was evaluated using a platelet function analyzer and impedance aggregometry (days 0, 14, and 28) for dogs treated with placebo, clopidogrel (2-3 mg/kg/d), prednisone (2 mg/kg/d), or prednisone with clopidogrel PO for 28 days. Results were categorized as nonresponder versus responder (platelet function analyzer), and inadequate, ideal, or excessive response (aggregometry). Results were compared using mixed model, split-plot repeated measures analysis of variance and generalized estimating equation proportional odds models. P < .05 was considered significant. Results: Closure times differed by treatment (F [3, 20] = 10.5; P < .001), time (F [2, 40] = 14.3; P < .001), and treatment-by-time (F [6, 40] = 3.4; P = .01). Area under the curve (AUC) differed by treatment (F [3, 20] = 19.6; P < .001), time (F [2, 40] = 35.4; P < .001), and treatment-by-time (F [6, 40] = 13.5; P < .001).Based on closure times, 5/6 dogs each in the clopidogrel and prednisone/clopidogrel groups were responders. All dogs in the prednisone/clopidogrel group were overcontrolled based on AUC (days 14 and 28), whereas 5/6 (day 14) and 2/6 (day 28) dogs treated with clopidogrel were overcontrolled. Compared to clopidogrel, dogs receiving prednisone/clopidogrel were 11 times (P = .03) more likely to have an excessive response.Conclusions and Clinical Importance: Administration of clopidogrel/prednisone increases platelet dysfunction in healthy dogs. K E Y W O R D S antiplatelet, corticosteroid, glucocorticoid, immune-mediated hemolytic anemia, thromboprophylaxis Abbreviations: AUC, area under the curve; IMHA, immune-mediated hemolytic anemia; RI, reference intervals.

Whole blood platelet impedance aggregometry with the ROTEM platelet device: comparison of 2 anticoagulants and storage times for the establishment of canine reference intervals

“…AUC decreased significantly in dogs treated with clopidogrel and tested in a Multiplate analyzer using ADP as agonist, and therefore, distinguishing impaired from normal platelet function is still possible. 43,47 Poor correlation of methods of platelet function testing in dogs was identified comparing thromboelastographic platelet mapping to whole blood platelet aggregometry with the Multiplate analyzer and platelet function analysis using citrated whole blood. It is suggested that population-based RIs are unsuitable for most platelet function tests, and that subject-based RIs are preferable because biological variation in platelet aggregation should be considered.…”

Anticoagulant effects of rivaroxaban, prednisone, alone and in combination, in healthy dogs

“…In healthy dogs, clopidogrel not only counteracts glucocorticoidinduced platelet reactivity, but that the combination of prednisone and clopidogrel enhances platelet dysfunction. 29 Although clopidogrel was shown to counteract glucocorticoid-induced hypercoagulability based on assessment of primary hemostasis, 29 this prior study did not focus on the mechanisms of glucocorticoid-induced hypercoagulability that could impact the efficacy of drugs that affect secondary hemostasis, such as rivaroxaban. The results of our current study suggest that the combination of rivaroxaban and prednisone does not significantly alter the overall anticoagulant effects of rivaroxaban.…”

Dental erosion following clopidogrel administration in a dog: A case‐based study

“…Clopidogrel has been used as an antiplatelet agent in dogs as an extralabel use (Plumb, 2018). A recent paper reported that the use of clopidogrel in combination with long‐term prescription of prednisolone could protect against glucocorticoid‐induced platelet reactivity in dogs (Thomason et al., 2020). Commercially available clopidogrel bisulphate is known to be practically insoluble in neutral water and has a pH‐dependent solubility (Kolbe et al., 2002; Plumb, 2018).…”