Thrombosis and haemostasis
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Idarucizumab is licensed for emergency reversal of dabigatran. A single 5 g dose is usually sufficient, but higher doses may sometimes be required and optimum dosing has not been defined. It was the aim of this study to investigate the effect of idarucizumab, given once or as a split dose, after double trauma in pigs anticoagulated with dabigatran. ⋯ Analysis of dabigatran plasma concentrations showed that equimolar concentrations of idarucizumab are necessary to bind all dabigatran and achieve sufficient thrombin generation. At sufficient doses, idarucizumab rapidly reduced blood loss and improved survival in this lethal porcine model of double trauma with dabigatran anticoagulation. In clinical practice, should bleeding continue after initial treatment with the approved 5 g dose of idarucizumab, a second dose may potentially be effective to control bleeding caused by redistribution of unbound dabigatran.
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Oral anticoagulation (OAC) is highly effective preventing stroke and mortality in AF, but withdrawal is common in the elderly, when high bleeding risk and when are difficulties achieving an optimal time in therapeutic range (TTR). We analysed the rate of OAC cessation, predisposing factors to cessation and the relation to clinical outcomes in a large 'real world' cohort of AF patients over a long follow-up period. Consecutive non-valvular AF outpatients clinically stables for six months were recruited. ⋯ Independent predictors of OAC cessation were age ≥80 (HR 2.29; 1.60-3.29), previous coronary artery disease (HR 0.32; 0.15-0.71), major bleeding (HR 5.00; 3.49-7.15), heart failure (HR 2.38; 1.26-4.47), cancer (HR 5.24; 3.25-8.44) and renal impairment developed during follow-up (HR 2.70; 1.26-5.75). In conclusion, in non-valvular AF patients, cessation of OAC was independently associated with the risk of stroke, adverse cardiovascular events and mortality. Bleeding events and some variables associated with higher bleeding risk are responsible for OAC cessation.
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Even though the Khorana risk score (KRS) has been validated to predict against the development of VTE among patients with cancer, it has a low positive predictive value. It is also unknown whether the score predicts outcomes in patients with cancer with established VTE. We selected a cohort of patients with active cancer from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry to assess the prognostic value of the KRS at inception in predicting the likelihood of VTE recurrences, major bleeding and mortality during the course of anticoagulant therapy. ⋯ The C-statistic was 0.53 (0.50-0.56) for recurrent VTE, 0.56 (95 %CI: 0.54-0.59) for major bleeding and 0.54 (95 %CI: 0.52-0.56) for death. In conclusion, most VTEs occur in patients with low or moderate risk scores. The KRS did not accurately predict VTE recurrence, major bleeding, or mortality among patients with cancer-associated thrombosis.
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Comparative Study
Distinctive expression signatures of serum microRNAs in ischaemic stroke and transient ischaemic attack patients.
Circulating microRNAs (miRNAs) have recently emerged as promising biomarkers for ischaemic stroke (IS). However, the expression patterns of specific miRNAs in transient ischaemic attack (TIA) patients have not been investigated. Their predictive values for the presence of IS and TIA and their relationships to the neurological deficit severity of IS and the subsequent stroke risk after TIA remain unclear exactly. ⋯ Strikingly, serum levels of miR-23b-3p, miR-29b-3p and miR-181a-5p were also significantly elevated in TIA patients. Furthermore, up-regulated miR-23b-3p, miR-29b-3p and miR-21-5p could clearly differentiate between IS and TIA patients. Logistic regression and receiver-operating characteristic curve analyses demonstrated that these altered miRNAs may function as predictive and discriminative biomarkers for IS and TIA, and their distinctive expression signatures may contribute to assessing neurological deficit severity of IS and subsequent stroke risk after TIA.
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Randomized Controlled Trial Multicenter Study Comparative Study
Prediction of major and clinically relevant bleeding in patients with VTE treated with edoxaban or vitamin K antagonists.
Better understanding of risk factors for major bleeding events during anticoagulant treatment for venous thromboembolism (VTE) may help physicians when deciding on intensity and duration of treatment. The primary aim of this study was to identify risk factors for major and clinically relevant bleeding in patients receiving the oral factor Xa inhibitor edoxaban or warfarin for the treatment of acute VTE. We analysed data from 8240 patients who received ≥1 dose of study drug in the Hokusai-VTE study. ⋯ The discrimination of the model was high (C-statistic: 0.71) for major bleeding, lower for clinically relevant bleeding (C-statistic: 0.62) and when the model was applied to patients receiving warfarin (C-statistic 0.60). In conclusion, we identified five main predictors of major bleeding in patients receiving edoxaban for the treatment of acute VTE. A risk model based on these factors predicted an increased risk of bleeding with good discrimination.