Thromb Haemostasis
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There is some data available on the role of high on-treatment platelet reactivity by ADP whereas, as regards arachidonic acid or other agonists, there is no proof of the best cut-off for identifying populations with a different cardiovascular outcome by the construction of appropriate receiver-operator characteristics (ROC) curves. We enrolled 1,108 acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI) with stent implantation and followed them up for 12 months. Platelet reactivity was assessed by light transmission aggregometry (LTA) using 10 microM ADP, 1 mM arachidonic acid (AA) and 2 microg/ml collagen. ⋯ The contemporary platelet hyperreactivity to more than one agonist was associated with a higher risk of 12-month cardiovascular death and MI, whereas isolated platelet hyperreactivity to only one agonist had not a predictive value [10 microM ADP LTA>or=55% + 1 mM AA LTA>or=15%: odds ratio [OR]=3.6(2.4-6.1), p<0.0001; ADP LTA>or=55% + 1 mM AA LTA>or=15% + 2 microg/ml collagen LTA>or=31%: OR=4.7(2.9-7.7), p<0.0001]. In this prospective study on a large number of acute coronary syndrome patients undergoing stent implantation, we have found that high on-treatment platelet reactivity measured by LTA induced by more than one agonist--AA, ADP, collagen--is an independent risk factor for 12-month cardiovascular death and non-fatal MI. Isolated platelet hyperreactivity to only one agonist has not a predictive value for clinical recurrences.
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Comparative Study
Comparison of methods for monitoring residual platelet reactivity after clopidogrel by point-of-care tests on whole blood in high-risk patients.
Cardiovascular events are more frequent in high-risk coronary artery disease (CAD) patients on dual antiplatelet therapy with a residual platelet reactivity (RPR) than in those showing inhibition of ADP-inducible platelet activation. It is known that post-interventional RPR is a clinically important entity confirming it as a risk factor for thrombo-ischaemic events. Multiple electrode platelet aggregometry (MEA) on whole blood has been recently proposed as a rapid tool to evaluate RPR in high-risk CAD patients on clopidogrel therapy. ⋯ MEA in relation to LTA showed a sensitivity of 80% and a specificity of 91%. MEA might represent a reliable method and valid alternative in comparison with other available platelet function assays. It might help to guide antiplatelet therapy and thus improve clinical outcome of high-risk CAD patients.
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Comparative Study
Prolonged effect of GlycoPEGylated rFVIIa (40k-PEG-rFVIIa) in rabbits correlates to activity in plasma.
The pharmacokinetics and pharmacodynamics of 40k-PEG-rFVIIa, a GlycoPEGylated derivative of recombinant wild-type FVIIa, were compared with rFVIIa in rabbits. The procoagulant effect was determined as the weight of the clot formed in a defined segment of a facial vein. A time course study was conducted where ligation was made 10 minutes, 12 or 24 hours after i.v. injection of equimolar doses of 40k-PEG-FVIIa or rFVIIa (2 mg/kg). ⋯ No consumption of platelets or fibrinogen was found and no thrombi formation was seen in histological examination of various organs. In conclusion, 40k-PEG-rFVIIa has shown prolonged duration of effect that correlated to various plasma markers and FVIIa clot activity. In perspective, the data support further clinical development of 40k-PEG-rFVIIa to potentially become a long-acting recombinant treatment option for prophylaxis in haemophilia patients with inhibitors.
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Dabigatran etexilate is an oral, reversible direct thrombin inhibitor that is approved in the EU and several other countries for the prevention of venous thromboembolism after elective hip and knee replacement, and is in advanced clinical development for other thromboembolic disorders. Dabigatran has a predictable pharmacokinetic profile, allowing for a fixed-dose regimen without the need for routine coagulation monitoring. In certain clinical situations such as serious bleeding into critical organs (e.g. intracerebral bleeding), potential overdose and emergency surgery, clinicians will need to make an assessment of the anticoagulant status of a patient receiving dabigatran before deciding on future management strategies. ⋯ In case of potential overdose, the feasibility of early administration of activated charcoal and subsequent charcoal filtration are undergoing preclinical evaluation. Dabigatran can also be dialysed in patients with renal impairment. In instances of life-threatening bleeding, where conventional measures have failed or are unavailable, other non-specific prohaemostatic agents such as recombinant activated factor VII and prothrombin complex concentrates can be considered.