Changes in platelet function in Dachshunds with early stages of myxomatous mitral valve disease.

The aim of this study was to evaluate platelet function in Dachshunds during early stages of myxomatous mitral valve disease. Clinical examination and echocardiography were performed in 34 wirehaired standard sized Dachshunds. Platelet function was evaluated using the PFA-100 (reported as closure time). In addition, whole blood platelet aggregation response and hemostatic markers were evaluated. Significant longer PFA-100 closure time (CT) was found in 12 Dachshunds with mild mitral regurgitation (MR) compared to 22 Dachshunds with minimal MR. Only five Dachshunds responded to adenosine diphosphate in the whole blood aggregation analyses. There were no differences between the two dog groups in plasma fibrinogen, plasma von Willebrand factor (vWf) or vWf multimer distribution; however, there was a significant correlation between CT and plasma vWf concentration and CT and plasma fibrinogen concentration. The higher CT found in Dachshunds with mild MR suggests a form of platelet dysfunction in Dachshunds with MR.

Body size, but neither age nor asymptomatic mitral regurgitation, influences plasma concentrations of dimethylarginines in dogs.

Asymmetric dimethylarginine (ADMA) is a marker of various cardiovascular diseases in man. The aim of the present study was to test if Cavalier King Charles Spaniels (CKCS) with varying degrees of mitral regurgitation (MR) had increased plasma concentration of ADMA and furthermore, characterize the plasma level of ADMA and symmetric dimethylarginine (SDMA) in normal dogs. Seventy-six dogs were included (44 CKCS and 32 dogs of other breeds). The CKCS had various degrees of MR, whereas the remaining dogs had either no or minimal MR. Apart from cardiac murmurs, no dogs showed signs of cardiac or systematic disease. The degree of MR had no significant influence on ADMA (P = 0.33). Body weight was directly associated with ADMA (P = 0.0004) and creatinine was directly associated with SDMA (P<0.0001). Furthermore, the plasma concentration of ADMA was three to four times higher than found in healthy humans.

Determinants of weak femoral artery pulse in dogs with mitral valve prolapse.

In three substudies encompassing 247 dogs from two breeds predisposed to myxomatous mitral valve disease (MMVD), femoral artery pulse strength was palpated and related to potential explanatory factors, including quantitative echocardiographic measures of MMVD, aortic and femoral artery diameter and wall thickness and blood pressure. In addition, in 109 Cavalier King Charles Spaniels (of which 61 were included in the three substudies mentioned above), the relation between femoral artery pulse strength and presence of thrombocytopenia was investigated. In 26% of the dogs, a pulse

Cardiac troponin I and T as prognostic markers in cats with hypertrophic cardiomyopathy.

BACKGROUND: Myocardial injury detected by cardiac troponin I and T (cTnI and cTnT) in cardiac disease is associated with increased risk of death in humans and dogs. HYPOTHESIS: Presence of myocardial injury predicts long-term death in cats with hypertrophic cardiomyopathy (HCM), and ongoing myocardial injury reflects change in left ventricular wall thickness over time. ANIMALS: Thirty-six cats with primary HCM. METHODS: Prospective cohort study. Cats with HCM were included consecutively and examined every 6 months. Echocardiography, ECG, blood pressure, and serum cTnI and cTnT were evaluated at each visit. Cox proportional hazards regression analysis was performed to evaluate prognostic potential of serum troponin concentrations at admission and subsequent examinations. Correlations were used to examine associations between troponin concentrations and cardiac hypertrophy. RESULTS: Troponin concentrations at admission were median [range] 0.14 [0.004-1.02] ng/mL for cTnI, and 13 [13-79.5] ng/L for cTnT. Both were prognostic for death (P = .032 and .026) as were the last available concentrations of each (P = .016 and .003). The final cTnT concentration was a significant predictor of death even when adjusting for the admission concentration (P = .043). In a model containing both markers, only cTnT remained significant (P = .043). Left ventricular free wall thickness at end-diastole (LVFWd) at admission was correlated with cTnI at admission (r = 0.35, P = .035), however no significant correlations (r = 0.2-0.31, P = .074-.26) were found between changes in troponin concentrations and left ventricular thickness over time. CONCLUSIONS AND CLINICAL IMPORTANCE: Myocardial injury is part of the pathophysiology leading to disease progression and death. Low sensitivities and specificities prevent outcome prediction in individual cats.

Prediction of long-term outcome by measurement of serum concentration of cardiac troponins in critically ill dogs with systemic inflammation.

BACKGROUND: Myocardial injury, detected by cardiac troponin I and T (cTnI and cTnT), has been associated with long-term death in the noncardiac human intensive care unit (ICU). HYPOTHESIS: Presence of myocardial injury predicts 1-year case fatality in critically ill dogs with systemic inflammation. ANIMALS: Thirty-eight dogs with evidence of systemic inflammation and no primary cardiac disease. METHODS: Prospective cohort study. In dogs admitted to the ICU with evidence of systemic inflammation, blood samples were obtained at ICU admission for measurement of cTnI and cTnT, and cTnI was measured once daily during ICU hospitalization. Receiver operating characteristic (ROC) curves were used to examine prognostic capacity of admission cTnI, admission cTnT, and peak cTnI concentrations. RESULTS: One-year case fatality rate was 47% (18/38 dogs). Admission cTnI concentrations were (median [range]) 0.48 [0.004-141.50] ng/mL, and peak cTnI concentrations were 1.21 [0.021-141.50] ng/mL. Admission cTnT concentrations were 15 [<13-3744] ng/L. For each marker, non-survivors had significantly higher concentrations than survivors (P = .0082-.038). ROC analyses revealed areas under curves [95% CI] of 0.707 [0.537-0.843] for peak cTnI and 0.739 [0.571-0.867] for admission cTnT, respectively. At the optimal cut-off, concentrations were 1.17 ng/mL (peak cTnI) and 23 ng/L (admission cTnT), sensitivities were 72% and 72%, and specificities were 70% and 80%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: While peak cTnI and admission cTnT are significantly related to 1-year case fatality in critically ill dogs with systemic inflammation, low sensitivities and specificities prevent their prediction of long-term outcome in individual patients. Troponins might play a role in identification of dogs at long-term risk of death.

Prognostic importance of myocardial injury in critically ill dogs with systemic inflammation.

BACKGROUND: In noncardiac critical disease in humans, myocardial injury as detected by cardiac troponin I and T (cTnI and cTnT) has been linked to high intensive care unit (ICU) death independent of prognostic composite scoring. HYPOTHESIS: Presence of myocardial injury predicts short-term death in critically ill dogs with systemic inflammation and provides additional prognostic information when combined with established canine prognostic composite scores. ANIMALS: Forty-two dogs admitted to the ICU with evidence of systemic inflammation and no primary cardiac disease. METHODS: Prospective cohort study. Blood samples were obtained at ICU admission for the measurement of cTnI and cTnT, C-reactive protein, and several cytokines. The acute patient physiologic and laboratory evaluation (APPLE) score and the survival prediction index were calculated within the first 24 hours of admission. Receiver operating characteristic (ROC) curves were used to examine the prognostic capacity of each biomarker and severity score. Multiple logistic regression analysis was performed to evaluate whether cardiac markers significantly contributed to severity scores. RESULTS: Twenty-eight day case fatality rate was 26% (11/42 dogs). cTnI concentrations were (median [range]) 0.416 [0.004-141.5] ng/mL and cTnT concentrations were 13.5 [<13-3,744] ng/L. cTnI, cTnT, and the APPLE score were all significant prognosticators with areas under the ROC curves [95% CI] of 0.801 [0.649; 0.907], 0.790 [0.637; 0.900], and 0.776 [0.621; 0.889], respectively. cTnI significantly contributed to the APPLE score in providing additional prognostic specificity (P = .025). CONCLUSIONS AND CLINICAL IMPORTANCE: Markers of myocardial injury predict short-term death in dogs with systemic inflammation and cTnI significantly contributes to the APPLE score.

Aspirin 'resistance': role of pre-existent platelet reactivity and correlation between tests.

BACKGROUND: Aspirin 'resistance' is a widely used term for hyporesponsiveness to aspirin in a platelet function test. Serum thromboxane (TX) B(2) is the most specific test of aspirin's effect on platelets. OBJECTIVES: (i) To examine the role of pre-existent platelet hyperreactivity in aspirin 'resistance'. (ii) To determine the correlation between aspirin resistance defined by serum TXB(2) and other assays of platelet function. METHODS: To enable pre-aspirin samples to be drawn, platelet function was measured in normal subjects (n = 165) before and after aspirin 81 mg daily for seven days. RESULTS: The proportion of the post-aspirin platelet function predicted by the pre-aspirin platelet function was 28.3 +/- 7.5% (mean +/- asymptotic standard error) for serum TXB(2), 39.3 +/- 6.8% for urinary 11-dehydro TXB(2), 4.4 +/- 7.7% for arachidonic acid-induced platelet aggregation, 40.4 +/- 7.1% for adenosine diphosphate-induced platelet aggregation, 26.3 +/- 9.2% for the VerifyNow Aspirin Assay, and 45.0 +/- 10.9% for the TEG PlateletMapping System with arachidonic acid. There was poor agreement between aspirin-resistant subjects identified by serum TXB(2) vs. aspirin-resistant subjects identified by the other five assays, irrespective of whether the analysis was based on categorical or continuous variables. Platelet count correlated with pre-aspirin serum TXB(2) and VerifyNow Aspirin Assay, but not with any post-aspirin platelet function test. CONCLUSIONS: (i) Aspirin 'resistance' (i.e. hyporesponsiveness to aspirin in a laboratory test) is in part unrelated to aspirin but is the result of underlying platelet hyperreactivity prior to the institution of aspirin therapy. (ii) Aspirin resistance defined by serum TXB(2) shows a poor correlation with aspirin resistance defined by other commonly used assays.

The active metabolite of prasugrel inhibits adenosine diphosphate- and collagen-stimulated platelet procoagulant activities.

BACKGROUND: Prasugrel is a novel antiplatelet prodrug of the same thienopyridine class as clopidogrel and ticlopidine. Metabolism of prasugrel generates the active metabolite R-138727, an antagonist of the platelet P2Y(12) adenosine diphosphate (ADP) receptor, leading to inhibition of ADP-mediated platelet activation and aggregation. ADP also enhances the platelet response to collagen, and these two agonists contribute to the generation of platelet procoagulant activity. We therefore examined whether R-138727 inhibits ADP- and collagen-triggered platelet procoagulant activities. METHODS AND RESULTS: As shown by whole blood flow cytometry, R-138727 inhibited surface phosphatidylserine expression on ADP plus collagen-stimulated platelets and tissue factor (TF) expression on ADP-, collagen-, and ADP plus collagen-stimulated monocyte-platelet aggregates. R-138727 reduced monocyte-platelet aggregate formation, thereby further inhibiting TF expression. ADP, collagen, and ADP plus collagen accelerated the kinetics of thrombin generation in recalcified whole blood and R-138727 significantly inhibited this acceleration. Clot strength in a modified thromboelastograph system was also inhibited by R-138727 (IC50 0.7 +/- 0.1 microM). CONCLUSIONS: In addition to its previously known inhibitory effects on platelet activation and aggregation, the active metabolite of prasugrel, R-138727, inhibits platelet procoagulant activity in whole blood (as determined by phosphatidylserine expression on platelets and TF expression on monocyte-platelet aggregates), resulting in the functional consequences of delayed thrombin generation and impaired clot development.