Thromb Haemostasis
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Editorial Comment
MicroRNAs in vascular biology--metabolism and atherosclerosis.
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The concept of net clinical benefit has been used to quantify the balance between risk of ischaemic stroke (IS) and risk of intracranial haemorrhage (ICH) with the use oral anticoagulant therapy (OAC) in the setting of non-valvular atrial fibrillation (AF), and has shown that patients at highest risk of stroke and thromboembolism gain the greatest benefit from OAC with warfarin. There are no data for the new OACs, that is, dabigatran, rivaroxaban and apixaban, as yet. We calculated the net clinical benefit balancing IS against ICH using data from the Danish National Patient Registry on patients with non-valvular AF between 1997-2008, for dabigatran, rivaroxaban and apixaban on the basis of recent clinical trial outcome data for these new OACs. ⋯ When risk of bleeding and stroke are both high, all three new drugs appear to have a greater net clinical benefit than warfarin. In the absence of head-to-head trials for these new OACs, our analysis may help inform decision making processes when all these new OACs become available to clinicians for stroke prevention in AF. Using 'real world' data, our modelling analysis has shown that when the risk of bleeding and stroke are both high, all three new drugs appear to have a greater net clinical benefit compared to warfarin.
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Comparative Study
Study of Octaplex dosing accuracy: an in vitro analysis.
Prothrombin complex concentrates (PCC) are recommended for urgent warfarin reversal. However, disagreement exists regarding the proper dosing strategy (i.e. fixed vs. weight-based). We measured the in vitro effect of PCC dosing on international normalised ratio (INR) and factor activity. ⋯ Factor IX did not uniformly correct above 0.50 IU (0.31-1.31). We confirm in vitro that 1,000 IU of Octaplex(®) is able to correct INR to <1.5 but factors were not uniformly >0.50 IU until 2,000 IU, and not >1.00 IU until 3,000 IU. This suggests that INR correction alone may not accurately reflect factor activity, and lends support for weight-based dosing.
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Stress-induced hyperglycaemia is common during orthopaedic surgery. In addition, hyperglycaemia activates coagulation. The aim of the study was to assess whether stress-induced hyperglycaemia is associated with symptomatic or asymptomatic venous thromboembolism (VTE) following orthopaedic surgery. ⋯ Increased glucose levels after total hip replacement were associated with total VTE; adjusted odds ratio (OR) highest versus lowest quartile 1.9 (95% confidence interval [CI] 1.3 to 3.0). Furthermore, increase in glucose levels during total hip replacement was associated with total VTE (OR highest versus lowest quartile 1.8 (95%CI 1.2 to 2.8). This was not observed in patients undergoing total knee replacement, probably due to differences in the applied surgical procedures.
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Edoxaban, an oral, direct factor Xa inhibitor, has a similar or low incidence of bleeding events compared with other anticoagulants in clinical trials. Therefore, agents to reverse the anticoagulant effects of edoxaban could be desirable in emergency situations. In this study, the reversal effects of haemostatic agents were determined on prothrombin time (PT) prolongation in vitro and bleeding time prolongation in vivo by edoxaban. ⋯ Among these, rFVIIa and Feiba showed potent activities in reversing the PT prolongation by edoxaban. rFVIIa (1 and 3 mg/kg, i.v.) and Feiba (100 U/kg, i.v.) significantly reversed edoxaban (1 mg/kg/h)-induced prolongation of bleeding time in rats. In a rat venous thrombosis model, no potentiation of thrombus formation was observed when the highest dose (3 mg/kg) of rFVIIa was added to edoxaban (0.3 and 1 mg/kg/h) compared with the control. The present study indicated that rFVIIa, Feiba, and PPSB-HT have the potential to be reversal agents for edoxaban.