Platelet activation and thrombus formation relates to the presence of myocardial inflammation in patients with cardiomyopathy.

BACKGROUND: Patients with cardiomyopathy show a significantly increased risk for thromboembolic events due to a hypercoagulable state and platelet dysfunction. The pathophysiologic mechanism underlying the increasing platelet activity in patients with cardiomyopathy remains unclear. We performed a clinical study to elucidate the link between myocardial tissue alterations and platelet activation in patients with cardiomyopathy. METHODS: A total of 30 patients with suspected cardiomyopathy and 10 healthy control patients were included in our study. Hemodynamic parameters were measured by catheterization and echocardiography. Endomyocardial biopsies were taken to determine myocardial inflammation. Flow cytometry was performed to examine the platelet activation by quantification of p-selectin and thrombospondin expression on platelets. RESULTS: The p-selectin (8.46 ± 3.67 AU) and thrombospondin (26.56 ± 23.21 AU) expression was significantly correlated with the amount of CD3+ T cells (p-selectin: r=0.573, p<0.05; thrombospondin: r=0.488, p<0.05) and the endothelial/interstitial activation (p-selectin: r=0.521, p<0.05; thrombospondin: r=0.39, p<0.05). This was found to be independent of hemodynamic parameters, age, and gender. The platelet activation of patients (n=3) with echocardiographically documented ventricular thrombi was significantly increased (p-selectin: 12.57 ± 5.5 AU vs. 8.1 ± 3.2 AU, p<0.05) and this was associated with elevated myocardial inflammation scores. CONCLUSION: Myocardial inflammation is associated with a significant increase in platelet activation and ventricular thrombus formation independently of the hemodynamic conditions.

Abciximab therapy is associated with increased platelet activation and decreased heparin dosage in patients with acute myocardial infarction.

The inhibition of the glycoprotein (GP) IIb/IIIa receptor for reducing periprocedural ischemic events in patients undergoing coronary intervention is known to influence platelet reactivity. Suboptimal doses of GP IIb/IIIa antagonists have been suggested to be prothrombotic and proinflammatory. This study was performed to observe platelet activation markers, whole blood aggregation and the dosage of unfractionated heparin (UFH) in the presence or absence of the GP IIb/IIIa inhibitor abciximab. Patients with acute myocardial infarction undergoing percutaneous coronary intervention were treated with (n = 15) or without (n = 15) abciximab. Platelet activation markers were flow cytometrically measured before and after PCI. Whole blood platelet aggregation was tested by a platelet function assay. The patients with abciximab showed a significant increase in platelet activation markers (P-selectin: 7.12 +/- 0.36 AU vs 11.05 +/- 0.79 AU) and a lower requirement of UFH to prolong aPTT > 60 sec during the infusion. 12 hours after infusion P-selectin level decreased (7.20 +/- 0.58 AU), whereas whole blood aggregation was increasing again. After stopping abciximab, requirement of UFH to prolong aPTT increased in the treated group to a greater extent to a level similar to the untreated group even when most of the platelets were still inhibited. The increased platelet activation found at the end of abciximab treatment points to a procoaguable condition that should be carefully monitored and treated by adapting anticoagulation and antiplatelet drugs.

ADP induced platelet degranulation in healthy individuals is reduced by clopidogrel after pretreatment with atorvastatin.

Statins inhibit platelet reactivity and reduce blood thrombogenicity. The effectiveness of clopidogrel in inhibiting platelet reactivity was suggested to be reduced in the presence of atorvastatin due to shared enzymes in metabolism. Healthy individuals, 17 pretreated with atorvastatin (20 mg/d for 3 days) and 17 without pretreatment, as well as 15 patients with stable coronary artery disease (CAD) and concurrent atorvastatin therapy were started on clopidogrel (loading dose 300 mg, then 75 mg/d). P-selectin on platelet surface after stimulation with ADP or Thrombin Receptor Activating Peptide (TRAP) was flow cytometrically measured before and during clopidogrel administration. Whole blood platelet agglutination was tested by a platelet function assay.TRAP and - in trend - ADP induced p-selectin exposure was reduced by the atorvastatin pretreatment before clopidogrel was added. Combining clopidogrel with atorvastatin in the healthy individuals led to a further reduction in ADP-induced platelet p-selectin exposure. Clopidogrel also reduced platelet reactivity in CAD patients with concurrent atorvastatin medication. We conclude that pretreatment with atorvastatin reduces platelet reactivity before administration of clopidgrel. No drug interaction was seen, however, platelet inhibitory effects were observed during the treatment with clopidogrel and atorvastatin.

Platelet activation is increased in patients with cardiomyopathy: myocardial inflammation and platelet reactivity.

Thrombotic events are a major complication in patients with cardiomyopathy, in which inflammation is often found within the heart. We examined the platelet activation in patients with cardiomyopathy with and without myocardial infiltrates. Endomyocardial biopsies of 45 patients with cardiomyopathy (CM) were immunohistologically assessed for infiltrates. Twenty-three patients had myocardial infiltrates (>/= 2 CD3(+) cells/high power field (HPF), CM+) and 22 patients had no inflammation (< 2 CD3(+) cells/HPF, CM-). Platelet adhesion proteins were flow cytometrically quantified (thrombospondin, P-selectin, CD 41) and platelet activation in CM compared to 45 healthy controls. Significantly more activated platelets were detected in patients with cardiomyopathy than controls (for thrombospondin 13.5% [10.3; 22.0] median [25; 75 quartile] vs. 10.6% [8.2; 16.0], P = 0.002; for P-selectin 12.6% [10.0; 18.6] vs. 7.7% [5.8; 10.9], P < 0.001). Platelet activation was higher in patients with cardiomyopathy and myocardial infiltrates (for thrombospondin 19.0% [11.0; 26.3]) compared to patients without inflammation (12.3% [9.9; 16.0], P = 0.018). Platelet GPIIb/IIIa expression was also increased in patients with inflammation (290 arbitrary units [268, 338]) compared to the controls (215 [188, 248], P < 0.001). In conclusion, platelet reactivity was increased in patients with cardiomyopathy and myocardial infiltrates. Measurement of platelet reactivity may be useful to identify patients with cardiomyopathy at risk for thrombotic events.