Dogs with Heart Diseases Causing Turbulent High-Velocity Blood Flow Have Changes in Platelet Function and von Willebrand Factor Multimer Distribution

Abstract

The purpose of this prospective study was to investigate platelet function using in vitro tests based on both high and low shear rates and von Willebrand factor (vWf) multimeric composition in dogs with cardiac disease and turbulent high-velocity blood flow. Client-owned asymptomatic, untreated dogs were divided into 4 groups: 14 Cavalier King Charles Spaniels (Cavaliers) with mitral valve prolapse (MVP) and no or minimal mitral regurgitation (MR), 17 Cavaliers with MVP and moderate to severe MR, 14 control dogs, and 10 dogs with subaortic stenosis (SAS). Clinical examinations and echocardiography were performed in all dogs. PFA100 closure times (the ability of platelets to occlude a hole in a membrane at high shear rates), platelet activation markers (plasma thromboxane B2 concentration, platelet surface P-selectin expression), platelet aggregation (in whole blood and platelet-rich plasma with 3 different agonists), and vWf multimers were analyzed. Cavaliers with moderate to severe MR and dogs with SAS had longer closure times and a lower percentage of the largest vWf multimers than did controls. Maximal aggregation responses were unchanged in dogs with SAS but enhanced in Cavaliers with MVP (regardless of MR status) compared with control dogs. No significant difference in platelet activation markers was found among groups. The data suggest that a form of platelet dysfunction detected at high shear rates was present in dogs with MR and SAS, possibly associated with a qualitative vWf defect. Aggregation results suggest increased platelet reactivity in Cavaliers, but the platelets did not appear to circulate in a preactivated state in either disease.

Evaluation of coagulation and platelet activation state and function in heartworm‐infected dogs

“…This hypothesis was partly derived from a publication evaluating the effects of turbulent high-velocity blood flow on platelet function in dogs with mitral valve insufficiency. 24 In these dogs, platelet dysfunction was apparent as prolonged PFA-100 closure times and accompanied by decreased circulating large vWf multimers, suggesting that turbulent blood flow or high shear conditions may enhance proteolysis of more functional multimers by ADAMTS-13, leading to a qualitative loss of function. We did not measure specific multimeric structures, nor did we investigate the presence of qualitative abnormalities in this study, but this may be of interest for further characterizing the impact of HWI on vWF.…”

No impact of polymorphism in the phosphodiesterase 5A gene in Cavalier King Charles Spaniels on pimobendan‐induced inhibition of platelet aggregation response

“…Previous research also has found associations between platelet count and platelet aggregation response in CKCS using various methodologies. Some found that low platelet count in CKCS was associated with a more hypercoagulable pattern, 36 others found that platelet count was positively associated with aggregation response 9 and no association between platelet count and aggregation response also has been reported 37,38 . Approximately one third of CKCS have inherited macrothrombocytopenia, which usually is not associated with clinical signs of disease 25,28,39 .…”

“…Some found that low platelet count in CKCS was associated with a more hypercoagulable pattern, 36 others found that platelet count was positively associated with aggregation response 9 and no association between platelet count and aggregation response also has been reported. 37,38 Approximately one third of CKCS have inherited macrothrombocytopenia, which usually is not associated with clinical signs of disease. 25,28,39 The reason for including the echocardiographic variable LV FS among variables with possible influence on basal aggregation and the effect of pimobendan on aggregation response is that a previous study indicated that increasing LV FS was associated with hypercoagulability based on thromboelastography in CKCS.…”

Platelet proteome changes in dogs with congestive heart failure

“…During the progression of CHF, turbulent high velocity blood ow and changes in blood shear stress around the degenerative mitral valve lea ets may produce platelet activation in dogs (4,5). Although clinical relevance of the platelet activation is not clear (6), some studies in this species have shown that activated platelets might contribute to the disease progression and an increased risk of sudden death by development of intra-myocardial coronary arteriosclerosis and micro-thrombi due to CHF (4-8). Therefore platelets may play an important role in development and progression of cardiovascular diseases (CVDs) in dogs with or without overt-thromboembolism (7) as occurs in humans (9).…”