Thromb Haemostasis
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Acetylsalicylic acid (ASA) and the thienopyridine clopidogrel are established anti-platelet drugs that significantly reduce secondary cardiovascular events in patients with manifest atherosclerosis. However, their impact on atherosclerotic lesion development remains controversial. Four-week-old ApoE-deficient mice were randomly assigned to four groups receiving a cholesterol diet together with either ASA (5 mg/kg), or clopidogrel (25 mg/kg), or a combination of both ASA and clopidogrel, or vehicle for 8-12 weeks. ⋯ However, therapy with ASA or clopidogrel alone, or in combination for a period of 8-12 weeks had no significant effect on adhesion of platelets to dysfunctional endothelial cells or on atherosclerotic lesion formation in the aortic root or the carotid artery. In conclusion, anti-platelet therapy is effective in reducing platelet adhesion and subsequent thrombus formation following rupture of atherosclerotic plaque in vivo. However, our data do not support a role of either drug in the primary prevention of atherosclerosis in ApoE-deficient mice.
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Randomized Controlled Trial
Effect of clopidogrel treatment on stress-induced platelet activation and myocardial ischemia in aspirin-treated patients with stable coronary artery disease.
Stress may counteract responses to antiplatelet drug treatment. We investigated if adding clopidogrel to aspirin treatment could attenutate stress-induced platelet activation and myocardial ischemia in patients with coronary artery disease (CAD). Thirty-one male patients with documented CAD-treated with aspirin (75-160 mg daily) were randomized to co-treatment with clopidogrel (n = 16) or placebo (n = 15). ⋯ Addition of clopidogrel to aspirin treatment did not attenuate either ambulatory or exercise-induced ischemia. In conclusion, adding clopidogrel to aspirin treatment inhibited platelet activation by both ADP, thrombin and collagen in vitro, but did not influence the prothrombotic responses to exercise. Intensified antiplatelet treatment did not reduce ECG signs of either exercise-induced or ambulatory myocardial ischemia.
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Multicenter Study Clinical Trial
Risk stratification and heparin prophylaxis to prevent venous thromboembolism in pregnant women.
Women with a history of venous thromboembolism (VTE), thrombophilia or both may be at increased risk of thrombosis during pregnancy, but the optimal management strategy is not well defined in clinical guidelines because of limited trial data. A strategy of risk assessment and heparin prophylaxis was evaluated in pregnant women at increased risk of VTE. In a prospective trial (Efficacy of Thromboprophylaxis as an Intervention during. ⋯ There was no evidence of heparin-induced thrombocytopenia, one case of osteoporosis, and rates of miscarriage and stillbirth were similar to previous, retrospective studies. Risk-stratified heparin prophylaxis was associated with a low incidence of symptomaticVTE and few clinically important adverse events. Antepartum heparin prophylaxis is, therefore, warranted in pregnant women with idiopathic thrombosis or symptomatic thrombophilia.
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Comparative Study Clinical Trial
The significance of vasodilator-stimulated phosphoprotein for risk stratification of stent thrombosis.
Low-response to the P2Y12 adenosine diphosphate (ADP)-receptor antagonist clopidogrel was suggested to correspond to a higher incidence of stent thrombosis (ST). This prospective observational study assessed the capability of two platelet function assays, e.g. direct measurement of the phosphorylation status of vasodilator-stimulated phosphoprotein (VASP) and ADP-induced platelet aggregation for definition of the individual risk to develop ST. Ninety-nine patients with an elevated high risk to develop ST were enrolled. ⋯ Receiver- operator characteristic (ROC) curve analysis revealed a cut-off value for VASP-PRI of <48% to be associated with low risk of ST. In conclusion, determination of VASP phosphorylation is superior to conventional platelet aggregometry and angiographic parameters for assessing the risk of ST. Patients with a VASP-PRI >48% seem to have a significantly increased risk.
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Comparative Study Clinical Trial
Use of the pentasaccharide fondaparinux as an anticoagulant during haemodialysis.
No data about the use of the pentasaccharide fondaparinux, a highly selective indirect inhibitor of factor Xa, in patients treated with haemodialysis are available. Therefore, we investigated the pharmacokinetics and -dynamics of fondaparinux in 12 patients during haemodialysis. The anti-Xa activity (expressed as fondaparinux equivalent) was monitored, a semiquantitative clotting scale (SQCS) ranging from 0 (no visible traces of coagula) to 3 (complete clotting of the dialysis circuit) was applied, and the digital compression time necessary to achieve haemostasis at the puncture site was determined. ⋯ Mean digital compression time rose slightly during fondaparinux from 23.7 +/- 7.4 minutes to 24.8 +/- 7.5 minutes (P < 0.05) and, more important, six of the 12 patients reported minor bleeding problems during the interdialytic interval. Thus, fondaparinux can be used to prevent circuit clotting during haemodialysis; however, accumulation results in an interdialytic increase of anti-Xa activity. Therefore, fondaparinux should be reserved for patients requiring systemic anticoagulation on the days off dialysis.