Platelet Activation in Cats with Hypertrophic Cardiomyopathy

Abstract

BackgroundCats with hypertrophic cardiomyopathy (HCM) are at risk for development of systemic thromboembolic disease. However, the relationship between platelet activation state and cardiovascular parameters associated with HCM is not well described.ObjectivesTo characterize platelet activation by flow cytometric evaluation of platelet P‐selectin and semiquantitative Western blot analysis of soluble platelet‐endothelial cell adhesion molecule‐1 (sPECAM‐1).AnimalsEight normal healthy cats (controls) owned by staff and students of the School of Veterinary Medicine and 36 cats from the UC Davis Feline HCM Research Laboratory were studied.MethodsPlatelet‐rich plasma (PRP) was used for all flow cytometry studies. Platelet surface CD41 and P‐selectin expression were evaluated before and after ADP stimulation. sPECAM‐1 expression was evaluated by Western blot analysis of platelet‐poor plasma that had been stabilized with aprotinin. Standard echocardiographic studies were performed.ResultsResting platelets from cats with severe HCM had increased P‐selectin expression compared to controls, and expressed higher surface density of P‐selectin reflected by their increased mean fluorescence intensities (MFI). Stimulation with ADP also resulted in significantly increased P‐selectin MFI of platelets from cats with severe HCM. Increased P‐selectin expression and MFI correlated with the presence of a heart murmur and end‐systolic cavity obliteration (ESCO). sPECAM‐1 expression from cats with moderate and severe HCM was significantly increased above those of control cats.Conclusions and Clinical ImportanceP‐selectin and sPECAM expression may be useful biomarkers indicating increased platelet activation in cats with HCM.

Platelet Activation and Clopidogrel Effects on ADP‐Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3

“…This finding further suggests the conclusion that cats with genetic predisposition to HCM have procoagulant platelets that predispose them to intracardiac thrombi formation and increased risk for ATE. Platelet P‐selectin expression in this population of cats was generally higher than previously reported . The differences in results were likely because of the use of different CD62P antibodies, in vitro activation from sample handing and centrifugation, age and genetic differences between the studied populations.…”

“…Furthermore, the use of citrate as an anticoagulant might have inhibited PMV formation because low extracellular calcium concentration prevents activation of calcium‐dependent calpain, which facilitates PMV formation by degrading structural proteins such as actin‐binding protein . Because cats with severe HCM were demonstrated to have a significant increase in PMV, it is also possible that PMV formation could be associated with disease severity and that the lack of clinical HCM precluded any significant changes in PMV formation …”

“…Platelet reactivity predicts thromboembolic events associated with myocardial infarct and coronary stent implantation . Altered platelet function occurs in cats with HCM . Maine Coon cats with severe HCM because of a mutation (A31P) in the myosin‐binding protein C ( MYBPC3 ) gene have increased expression of P‐selectin, platelet‐derived microvesicles (PMVs), and platelet–endothelial cell adhesion molecule‐1 .…”

Characterization and in vivo performance of nitric oxide‐releasing extracorporeal circuits in a feline model of thrombogenicity

“…A systemic hypercoagulable state occurs in 50% of cardiomyopathic felines with spontaneous echocardiographic contrast (or “smoke”) with or without a left atrial (LA) thrombus, and in 56% of felines with ATE and LA enlargement . Thromboembolism in felines with CM is likely an effect resulting from platelet activation (due to altered blood flow and shear stress within the cardiovascular system) and coagulation factors (in areas of blood stasis within the left atrium) . This increased platelet activity in felines could provide a more rigorous model for the evaluation of the biocompatibility of materials.…”

Analytical validation of platelet microparticle quantification in cats

“…Evidence of hypercoagulability in cats presenting with CE exists, but the sensitivity of a single or several markers has been low. Studies using platelet aggregometry support an increased platelet activation level in cats with HCM, and one study demonstrated higher PMP concentrations among Maine Coon cats with severe HCM compared with those of healthy mixed‐breed cats . Further investigations into PMPs as a prothrombotic risk factor in HCM are warranted.…”