Thrombosis research
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Orally active direct inhibitors of thrombin and factor Xa have now been approved for treatment or prevention of deep vein thrombosis,and stroke associated with atrial fibrillation. The factor Xa inhibitor, rivaroxaban, has shown promising results in the treatment of acute coronary syndrome but is not yet approved for that indication. ⋯ These agents have fewer drug interactions than warfarin, have a predictable clearance, and hence do not require monitoring. Patients with renal insufficiency have delayed clearance and hence may have elevated levels of the drug leading to increased risk of bleeding.
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Despite improved clinical outcomes from dual anti-platelet therapy with aspirin plus the CYP12 ADP receptor antagonist clopidogrel in patients undergoing coronary revascularisation, ex-vivo platelet function testing consistently reveals a proportion of patients with apparent resistance or non-response to clopidogrel loading and maintenance therapy who are at increased risk of coronary thrombosis. Treatment regimens using the newer CYP12 antagonists prasugrel and ticagrelor demonstrate improved ex-vivo platelet inhibition and superior clinical efficacy in large-scale clinical trials-even in patients demonstrating clopidogrel resistance. ⋯ Therefore when deciding anti-platelet regimens in suspected acute coronary syndrome, particular consideration must be given to patient's risk of thrombosis (STEMI, previous stent thrombosis), the procedure (complex PCI, thrombus in-situ, strategy of pre-treatment), and factors affecting safety (patient age, patient weight, previous stroke, liklehood of surgical revascularisation). Placing the focus on individualised patient risk-benefit assessment with appropriate use of platelet function testing when indicated, in combination with the ongoing assessment of prasugrel and ticagrelor in larger numbers of patients should be the key strategies governing use of dual anti-platelet therapy.
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Thrombosis research · Oct 2012
Evaluation of ticagrelor pharmacodynamic interactions with reversibly binding or non-reversibly binding P2Y(12) antagonists in an ex-vivo canine model.
As ticagrelor, clopidogrel and cangrelor therapies may be used in the same clinical setting, their potential pharmacodynamic interactions are of interest. Hence, we investigated possible interactions between these agents in dogs using a variety of switching protocols. ⋯ The extent of the pharmacodynamic drug-drug interactions observed between clopidogrel and cangrelor or ticagrelor apparently depends on the level of receptor occupancy when clopidogrel is administered. Importantly, no significant pharmacodynamic interaction occurred between ticagrelor/clopidogrel when clopidogrel was given at clinical trough IPA levels with ticagrelor. No significant pharmacodynamic interaction occurred with cangrelor and ticagrelor.
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Thrombosis research · Oct 2012
Antithrombotic agents and invasive procedures--hematologist point of view.
The management of a patient treated with an antithrombotic agent who requires an invasive procedure remains challenging. There are antidotes neither for the antiplatelet agents nor the new anticoagulants. A good knowledge of basic pharmacology of these drugs and the help of a hematologist within a multidisciplinary approach are essential. The potential interest of laboratory tests and the use of reversal agents, and the transfusion of plasma and platelets will be discussed.
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Thrombosis research · Sep 2012
Multicenter Study Controlled Clinical TrialEmergency reversal of anticoagulation: the real use of prothrombin complex concentrates: a prospective multicenter two year French study from 2006 to 2008.
Prothrombin complex concentrate (PCC) for reversal of vitamin K antagonist (VKA) is the main therapeutic option in cases of life-threatening bleeding. Clinical use of PCC is poorly documented. ⋯ A suitable treatment was administered in 26% of patients. A PCC dose of 20-30 IU/kg seems adequate in most cases to reverse VKA activity, but both higher and lower doses achieve similar effects. Considerable progress is required to improve PCC administration and control of treatment efficacy, and to shorten time to diagnosis.