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Platelet activation in cats with HCM | VETgirl Veterinary CE Podcasts

In this VETgirl podcast, we review platelet activation in cats with hypertrophic cardiomyopathy (HCM). Arterial thromboembolism – more commonly known as saddle thrombus – in cats with HCM occurs secondary to intracardiac thrombi formation, believed associated with Virchow’s triad: underlying endocardial injury, blood stasis (e.g., left atrial blood flow), and a disease condition that predisposes towards a hypercoagulable state (e.g., cardiac disease, IMHA, neoplasia, etc.).

In human medicine, left ventricular hypertrophy is associated with spontaneous platelet activation, and an increase in expression of P-selectin (a cell adhesion molecule on activated platelets) has been identified in humans with congestive heart failure (CHF) and HCM. Cardiac conditions that result in increased shear forces create an environment of increased platelet activation, and limited evidence does exist that platelet activation is involved in thromboembolic disease in cats with HCM.

So Tablin et al out of UC Davis wanted to evaluate this. They looked at 8 clinically healthy cats (controls) and compared them to 36 Maine Coon (purebred or cross) cats from UC-Davis Feline HCM Research Laboratory. In this study, HCM was confirmed in cats via echocardiography and genotyping (A31P myosin-binding protein C mutation). Severe HCM was defined as a left ventricular wall thicknesses that was > 7 mm on echocardiogram. Platelet properties were evaluated via flow cytometry and Western blot analysis.

In this study, cats with severe HCM had statistically higher P-selectin-positive platelets, an increased mean fluorescence intensity (MFI) (indicator of platelet activation), and an increased CD41-positive platelet microvesicle population (indicator of platelet activation) when stimulated with ADP. There was no difference seen between control cats and cats with equivocal or moderate HCM, however.

Significant differences were seen in P-selectin positive platelets and MFI in cats with murmurs versus those cats without a murmur. Increased sPECAM-1 (indicator of platelet activation) was seen in cats with moderate to severe HCM. Overall, no differences were seen in plasma fibrinogen concentrations among all the groups. There was also no association of findings with Main Coon genotype.

So what’d this study find? This study identified increased platelet activation via multiple measurable parameters of platelet activation in cats with severe HCM. P-selectin, specifically, is identified on platelet surfaces following expression of alpha granules. It promotes platelet binding with other platelets as well as white blood cells (WBC) in the process of thrombus formation at the site of damaged endothelium. PECAM-1 is known to be proinflammatory and increased in humans with myocardial infarction and CHF. PECAM-1 is a marker for platelet activation but actually inhibits thrombus formation and may be a response to the elevated procoagulant platelet markers (nonetheless indicating activation). Some limitations of the study? There was a pretty small sample size and lack of Maine Coon control group.

So what does VETgirl take from this study?

This study nicely shows that multiple well-documented markers of platelet activation are increased in Maine Coon cats with severe HCM, supportive of a hypercoagulable state at the cellular level in these cats. This has potentially important clinical application given that the two most commonly used oral antithrombotic agents (e.g., clopidogrel and aspirin) used in cats with heart disease target platelets in their mechanism of action. Overall, platelet activation appears to be increased in Maine Coon cats with severe HCM, providing evidence for one potential etiology of hypercoagulability and the thromboembolic state in these cats. VETgirl’s message? Be more aggressive using anti-platelet drugs in cats – especially Maine Coons – with CHF and HCM!

References:

1. Tablin F, Schumacher T, Pombo M, et al. Platelet activation in cats with hypertrophic cardiomyopathy J Vet Intern Med 2014;28(2):411-418.

2. Smith SA, Tobias AH, Jacob KA, et al. Arterial thromboembolism in cats: acute crisis in 127 cases (1992-2001) and long-term management with low-dose aspirin in 24 casesJ Vet Intern Med 2003;17(1):73-83.

Abbreviations:

HCM: Hypertrophic cardiomyopathy

CHF: Congestive heart failure

sPECAM-1: circulating platelet soluble endothelial cell adhesion molecule-1

NOTE: We apologize for all the podcast background noise – construction on the street! It’ll only last 6 more months…

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