Thrombosis research
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Thrombosis research · Jul 2013
Platelet inhibition by abciximab bolus-only administration and oral ADP receptor antagonist loading in acute coronary syndrome patients: the blocking and bridging strategy.
Current guidelines still recommend the bolus and infusion administration of glycoprotein IIbIIIa inhibitors in patients with high-risk acute coronary syndrome undergoing percutaneous coronary intervention. We sought to evaluate the extent of platelet inhibition by a blocking and bridging strategy with intracoronary abciximab bolus-only administration and oral loading of adenosine diphosphate receptor antagonists. ⋯ Immediate blocking of platelet aggregation in high-risk acute coronary syndrome patients by intracoronary abciximab bolus-only administration and bridging to prolonged inhibition via oral blockade of ADP receptors effectively inhibited overall platelet reactivity for at least 48 h, questioning the value of continuous abciximab infusion. Co-medication with prasugrel vs. clopidogrel synergistically augmented platelet inhibition.
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Thrombosis research · Jun 2013
Randomized Controlled TrialDecreased platelet miR-223 expression is associated with high on-clopidogrel platelet reactivity.
We aimed to investigate the relationship between platelet microRNA (miR-223 and miR-96) expression and clopidogrel responsiveness in patients with coronary heart disease (CHD). ⋯ The present work identifies decreased platelet miR-223 expression as a novel mechanism involved in blunted platelet response to clopidogrel in a Chinese population.
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Thrombosis research · Jun 2013
Coronary Microvascular function, Peripheral Endothelial Function and Carotid IMT in beta-thalassemia minor.
Higher prevalence of cardiovascular disease in Thalassemia patients have been known. Potential mechanisms are enhanced platelet activation, LDL oxidation, macrophage activation, and increased nitric oxide destruction. We have investigated coronary flow reserve (CFR), brachial artery flow mediated dilation (FMD) and Carotid intima-media thickness (IMT) in patients with Beta thalessemia minor (BTM). ⋯ CFR reflecting coronary microvascular function and brachial artery FMD are decreased, and carotid IMT is increased in patients with BTM.
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Thrombosis research · Jun 2013
Impact of antithrombin deficiency on efficacy of edoxaban and antithrombin-dependent anticoagulants, fondaparinux, enoxaparin, and heparin.
Oral factor Xa (FXa) inhibitors are a novel class of anticoagulants that, unlike heparins, are expected to demonstrate antithrombotic effects independent of plasma antithrombin (AT) concentrations. We utilized heterozygous AT-deficient (AT+/-) mice to determine the impact of AT deficiency on anticoagulant and antithrombotic effects of edoxaban, a direct FXa inhibitor, and compared with heparins (fondaparinux, enoxaparin, and unfractionated heparin [UHF]). ⋯ Edoxaban may potentially be prioritized over AT-dependent anticoagulants in patients with lower plasma AT concentration.
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Thrombosis research · May 2013
Darexaban: anticoagulant effects in mice and human plasma in vitro, antithrombotic effects in thrombosis and bleeding models in mice and effects of anti-inhibitor coagulant complex and recombinant factor VIIa.
Here, we investigated the anticoagulant effects of darexaban in mice and human plasma in vitro, effects of darexaban in thrombosis and bleeding models in mice, and reversal effects of anti-inhibitor coagulant complex (ACC) and recombinant factor VIIa (rFVIIa) on anticoagulant effects of darexaban. In mice, darexaban inhibited FXa activity in plasma with an ED50 value of 24.8 mg/kg. Both darexaban and warfarin prolonged prothrombin time (PT) at 3 mg/kg and 0.3 mg/kg/day, respectively. ⋯ In a tail-transection mouse model, darexaban had no significant effect on the amount of blood loss at doses up to 10 mg/kg, while warfarin showed a dose-dependent increase in blood loss, significantly so from 1 mg/kg/day. Darexaban and its metabolite darexaban glucuronide significantly prolonged PT and aPTT in human plasma in vitro, and while rFVIIa concentration-dependently reversed the prolonged PT in this plasma, ACC dose-dependently reversed both PT and aPTT changes prolonged by darexaban. Taken together, these results suggest that darexaban has a potential to be an oral anticoagulant with a better safety profile than warfarin, and that rFVIIa and ACC may be useful as antidotes to darexaban in cases of overdose.