Thrombosis and haemostasis
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The protein C (PC) system conveys beneficial anticoagulant and cytoprotective effects in numerous in vivo disease models. The endothelial protein C receptor (EPCR) plays a central role in these pathways as cofactor for PC activation and by enhancing activated protein C (APC)-mediated protease-activated receptor (PAR) activation. During inflammatory disease, expression of EPCR on cell membranes is often diminished thereby limiting PC activation and APC's effects on cells. ⋯ Accordingly, EPCR painting supported PAR1 and PAR3 cleavage by APC and augmented PAR1-dependent Akt phosphorylation by APC. Thus, EPCR-GPI painting achieved physiological relevant surface levels on endothelial cells, restored APC binding to EPCR-depleted cells, supported PC activation, and enhanced APC-mediated PAR cleavage and cytoprotective signalling. Therefore, EPCR-GPI provides a novel tool to restore the bioavailability and functionality of EPCR on EPCR- depleted and -deficient cells.
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Review Meta Analysis
Anticoagulation strategies for venous thromboembolism: moving towards a personalised approach.
Four non-vitamin K antagonist oral anticoagulants (NOACs) have now been evaluated in clinical trials, providing new therapeutic options for the treatment of venous thromboembolism (VTE). Recent position statements call for a move towards tailored recommendations for the treatment of VTE, to better define in whom and under what conditions a particular anticoagulant may improve clinical outcomes. Here we review the phase III data on NOAC trials for the treatment of VTE, assessing the favourability of agents for particular patient subgroups and aetiologies. Where the data permit, individualised risks of recurrent VTE events and bleeding are presented.
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Randomized Controlled Trial Comparative Study
Onset of optimal P2Y12-ADP receptor blockade after ticagrelor and prasugrel intake in Non-ST elevation acute coronary syndrome.
Pretreatment with a loading dose (LD) of clopidogrel or ticagrelor before percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) is supported by the guidelines, but debated following a recent meta-analysis on clopidogrel pretreatment and the ACCOAST trial. In this trial prasugrel pretreatment failed to reduce ischaemic events. The timing of optimal platelet reactivity (PR) inhibition of ticagrelor and prasugrel in non ST-elevation ACS (NSTE ACS) is yet undetermined. ⋯ At that time, the mean VASP index was 19 ± 16% (95%CI: 12-25). Maximal PR inhibition was reached after 4 h: 11 ± 10% (95%CI: 6-15). In NSTE ACS undergoing PCI a LD of ticagrelor or prasugrel given during the procedure provides optimal P2Y12-ADP receptor blockade in 2 h and maximal inhibition within 4 h.
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Randomized Controlled Trial Multicenter Study Comparative Study
Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism. Rationale for and design of the EINSTEIN CHOICE study.
Patients with unprovoked venous thromboembolism (VTE) are at high risk for recurrence. Although rivaroxaban is effective for extended VTE treatment at a dose of 20 mg once daily, use of the 10 mg dose may further improve its benefit-to-risk ratio. Low-dose aspirin also reduces rates of recurrent VTE, but has not been compared with anticoagulant therapy. ⋯ The primary efficacy objective is to determine whether both doses of rivaroxaban are superior to aspirin for the prevention of symptomatic recurrent VTE, while the principal safety outcome is the incidence of major bleeding. The trial is anticipated to enrol 2,850 patients from 230 sites in 31 countries over a period of 27 months. In conclusion, the EINSTEIN CHOICE study will provide new insights into the optimal antithrombotic strategy for extended VTE treatment by comparing two doses of rivaroxaban with aspirin (clinicaltrials.gov NCT02064439).
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Clinical Trial Observational Study
Prevention of dipyrone (metamizole) induced inhibition of aspirin antiplatelet effects.
We have recently shown that dipyrone (metamizole), a non-opioid analgesic, can nullify aspirin (acetylsalicylic acid; ASA) antiplatelet effects in patients with coronary artery disease (CAD). In this study, we analysed the aspirin and dipyrone drug-drug interaction in order to identify strategies to prevent the dipyrone induced inhibition of asprin antiplatelet effects. Platelet function was measured by arachidonic acid-induced light-transmission aggregometry, thromboxane (TX) B2- formation by immunoassay. ⋯ In a cross-over designed study in four healthy individuals, we were able to prove that inhibition of aspirin (100 mg/ day) effects by dipyrone (750 mg/ day) was reversible. Furthermore, aspirin (100 mg/ day) medication prior to dipyrone (750 mg/ day) intake prevented the inhibition of antiplatelet effects by dipyrone in 12 healthy individuals. In conclusion, aspirin medication prior to dipyrone intake preserves antiplatelet effects, circumventing the pharmacodynamic drug-drug interaction at the level of cyclooxygenase-1.