C15 - Evaluation of Platelet Activation, Platelet-leukocyte Interaction, and Hemostasis in Dogs with Pulmonary Hypertension

Background - The role of platelets (PLT) and their immune function in pulmonary hypertension (PH) remain poorly understood. Evidence in humans suggests vascular changes are secondary to PLT activation and thrombosis.

Hypothesis/Objectives - To assess PLT activation, PLT-leukocyte interactions and thromboelastography (TEG) in dogs with PH.

Animals - 29 client-owned dogs. Group 1 = 5 dogs with PH secondary to myxomatous mitral valve disease (MMVD), and 10 control MMVD dogs without PH. Group 2 = 5 dogs with PH due to respiratory diseases and 4 dogs with PH due to other causes, and 5 control dogs with respiratory diseases only.

Methods- Prospective observational case-control study. PH diagnosis was based on ACVIM guidelines. Dogs underwent echocardiogram, thoracic radiographs, heartworm antigen test, TEG, and flow cytometry for PLT P-selectin expression and PLT-leukocyte interaction. Platelet activation and PLT-leukocyte aggregates were measured as P-selectin median fluorescence intensity (MFI) and percent-positive events.

Results- Dogs with MMVD and PH had augmented PLT response to ADP (7153±4673 vs. 3110±1328, p=0.021) and thrombin (14,126±4280 vs. 5374±2648, p=0.0003) compared to control MMVD dogs. PH dogs in Group 2 also had augmented thrombin-mediated activation compared to controls (20588±31693 vs 4864±1364, p=0.02). Platelet-leukocyte interaction was higher following ADP-induced activation in MMVD dogs with PH (25.01%±15.24 vs. 12.92%±4.18, p=0.04). No significant differences were found in any TEG parameters between dogs with and without PH.

Conclusion and clinical importance - Platelets are hyper-reactive in dogs with PH, thereby, increasing platelet-leukocyte aggregate formation. Platelet-leukocyte interaction likely plays a role in the pathogenesis of PH in dogs.