2024 journal article

Platelet hyperresponsiveness and increased platelet‐neutrophil aggregates in dogs with myxomatous mitral valve disease and pulmonary hypertension

Journal of Veterinary Internal Medicine.

By: L. Duler*, L. Visser*, N. Nguyen*, L. Johnson*, J. Stern n & R. Li*

Source: ORCID
Added: June 1, 2024

Abstract Background Pulmonary hypertension (PH) in dogs with myxomatous mitral valve disease (MMVD) is caused by increased pulmonary venous pressure. Thrombosis, vascular remodeling, and vasoconstriction mediated by platelets could exacerbate PH. Hypothesis Dogs with PH will exhibit a hypercoagulable state, characterized by increased platelet activation, platelet‐leukocyte, and platelet‐neutrophil aggregate formation. Animals Eleven dogs (≥3.5 kg) diagnosed with MMVD and PH and 10 dogs with MMVD lacking PH. Methods Prospective cohort ex vivo study. All dogs underwent echocardiographic examination, CBC, 3‐view thoracic radiographs, and heartworm antigen testing. Severity of PH and MMVD were assessed by echocardiography. Viscoelastic monitoring of coagulation was assessed using thromboelastography (TEG). Platelet activation and platelet‐leukocyte/platelet‐neutrophil interactions were assessed using flow cytometry. Plasma serotonin concentrations were measured by ELISA. Results Unstimulated platelets from dogs with MMVD and PH expressed more surface P‐selectin than MMVD controls ( P = .03). Platelets from dogs with MMVD and PH had persistent activation in response to agonists. The number of platelet‐leukocyte aggregates was higher in dogs with MMVD and PH compared with MMVD controls ( P = .01). Ex vivo stimulation of whole blood resulted in higher numbers of platelet‐neutrophil aggregates in dogs with MMVD and PH ( P = .01). Assessment of hypercoagulability based on TEG or plasma serotonin concentrations did not differ between groups. Conclusion and Clinical Importance Platelet hyperresponsiveness and increased platelet‐neutrophil interaction occur in dogs with MMVD and PH, suggesting that platelets play a role of in the pathogenesis of PH. Clinical benefits of antiplatelet drugs in dogs with MMVD and PH require further investigation.