Thromb Haemostasis
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Comparative Study
Comparison of calibrated dilute thrombin time and aPTT tests with LC-MS/MS for the therapeutic monitoring of patients treated with dabigatran etexilate.
Ways to monitor dabigatran etexilate (DE) therapy would be useful in certain situations. Functional assays such as aPTT or Hemoclot® Thrombin Inhibitor (HTI) have been proposed to evaluate dabigatran concentrations, but previous findings are based on in vitro studies and results must be confirmed in clinical samples. The aim of this study was to compare aPTT and HTI measurements with liquid chromatography-tandem mass spectrometry (LC-MS/MS) measurements of dabigatran in plasma samples from DE treated patients. ⋯ In conclusion, the poor sensitivity, the important inter-individual variability, and the poor correlation with LC-MS/MS preclude the use of aPTT to estimate dabigatran concentrations. Due to its small inter-individual variability and good agreement with LC-MS/MS measurements, we recommend the use of HTI assays to rather accurately estimate concentrations of dabigatran >50 ng/ml. Quantification of lower dabigatran levels in DE-treated patients requires the "reference" LC-MS/MS method.
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Venous thromboembolism (VTE) may complicate the clinical course of glioblastoma multiforme (GBM). Circulating microparticles (MPs) have been associated with cancer-related VTE. Sixty-one consecutive patients with GBM undergoing gross-total (41) or subtotal (20) surgical resection followed by radio-chemotherapy were prospectively evaluated. ⋯ TF+/GFAP- MPs levels above the 90th percentile (calculated in GBM patients without VTE) were associated with a higher risk of VTE (RR 4.17, 95% CI 1.57-11.03). In conclusion, the numbers of glial-derived and/or TF-bearing MPs were high in GBM patients both before and even more after the neoplasm was treated, especially in patients with subtotal resection likely according to disease progression. A contribution of TF+/GFAP- MPs to the risk of VTE is suggested.
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Atrial fibrillation (AF) is associated with a significantly increased stroke risk which is highly preventable with appropriate oral anticoagulant therapy (OAC). However, AF may be asymptomatic and unrecognised prior to stroke. We aimed to determine if single time-point screening for AF could identify sufficient numbers with previously undiagnosed AF, to be effective for stroke prevention. ⋯ Screening can identify 1.4% of the population ≥65 years with previously undiagnosed AF. Many of those identified would be eligible for, and benefit from OAC to prevent stroke. Given this incidence, community AF screening strategies in at risk older age groups could potentially reduce the overall health burden associated with AF.
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Antithrombotic drugs like vitamin K antagonists and heparin have been the gold standard for the treatment and prevention of thromboembolic disease for many years. Unfortunately, there are several disadvantages of these antithrombotic drugs: they are accompanied by serious bleeding problems, it is necessary to monitor the therapeutic window, and there are various interactions with food and other drugs. This has led to the development of new oral anticoagulants, specifically inhibiting either thrombin or factor Xa. ⋯ We analysed epidemiological data concerning thrombosis and bleeding in patients deficient in one of the intrinsic pathway proteins. Furthermore, we discuss several thrombotic models in intrinsic coagulation factor-deficient animals. The combined results suggest that intrinsic coagulation factors could be suitable targets for anticoagulant drugs.