Increased Platelet Aggregation Response in Cavalier King Charles Spaniels with Mitral Valve Prolapse

Abstract

Mitral valve prolapse (MVP) is a fundamental feature of myxomatous mitral valve disease in the dog. In humans, primary MVP is associated with increased platelet reactivity. In Cavalier King Charles Spaniels (CKCS), a breed predisposed to myxomatous mitral valve disease, there is a high prevalence of hypomagnesemia and platelet anomalies, such as thrombocytopenia and macrothrombocytosis. The objective of this study was to evaluate platelet aggregation responses in CKCS and to determine the relationship between the platelet aggregation response and serum magnesium concentration, MVP, mitral regurgitation (MR), and platelet count. In 19 CKCS with MVP and 7 control dogs (not CKCS), the platelet aggregation response to 3 different agonists was compared. The CKCS with >100,000 platelets/microL (n = 10) had a significantly higher maximum aggregation response with regard to all tested agonists than the CKCS with <100,000 platelets/microL (n = 9) and control dogs (n = 7). The CKCS with <100,000 platelets/microL had a platelet aggregation response similar to the control dogs. There was no correlation between degree of MVP and platelet aggregation response. Platelet diameter increased (P = .006) and serum magnesium concentration decreased (P = .04) with lower platelet concentration. In conclusion, CKCS with MVP appeared to separate into 2 groups--1 group with <100,000 platelets/microL, normal platelet aggregation, low serum magnesium concentration, and enlarged platelets, and another group with >100,000 platelets/microL, increased platelet aggregation, and normal serum magnesium concentration and platelet size.

Serum Serotonin Concentrations in Dogs with Degenerative Mitral Valve Disease

“…In CKCS, the ultrastructure of the giant platelets appears normal by electron microscopy, 33 but the actual 5HT content in the dense granules is unknown. Previous studies failed to find a correlation between the presence of macrothrombocytes and DMVD, 37,39 which is consistent with our results indicating that serum 5HT was similarly increased in CKCS regardless of the presence of macrothrombocytes.…”

“…Thus, the hypothesis that canine valve injury may attract circulating platelets, which subsequently release 5HT and increase local 5HT signaling warrants further investigation. Also, approximately one‐third of CKCS possess macrothrombocytes, 33 and several complex alterations in platelet and hemostatic function have been described in dogs with DMVD 33–38 . In CKCS, the ultrastructure of the giant platelets appears normal by electron microscopy, 33 but the actual 5HT content in the dense granules is unknown.…”

Comparison of methods for determining platelet numbers and volume in cavalier King Charles spaniels

“…Similar to Mediterranean macrothrombocytopenia, macrothrombocytosis and low platelet count in CKCS is a clinically asymptomatic IGPD (Cowan and others 2004). The association between this platelet dysplasia and several vascular diseases described in CKCS (Beardow and Buchanan 1993, Buchanan and others 1997, Karlstam and others 2000) and other disorders (for example, deafness) has not been clarified yet (Olsen and others 2001, Cowan and others 2004).…”

Insights into Serotonin Signaling Mechanisms Associated with Canine Degenerative Mitral Valve Disease

“…These alterations are likely to attract platelets to the valve surface, and scanning electron microscopy studies of affected canine 68 and human 69,70 mitral valves show small numbers of platelets adhered to areas of endothelial damage. The aggregation potential of platelets in dogs with DMVD has been variably reported as decreased 71 or increased 72 by different investigators, and additional studies are needed to better define if, how, and to what extent platelet adhesion, aggregation, and 5HT release play a role in the initiation or progression of valve injury.…”