Thromb Haemostasis
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Neutrophil gelatinase-associated lipocalin (NGAL) is an increasingly used biomarker for acute kidney injury (AKI). Its utility in adult patients with AKI caused by Shiga toxin producing Escherichia coli infection (STEC)-associated haemolytic-uraemic syndrome (HUS), remains unknown. We aimed to evaluate the prognostic value of serum NGAL admission levels for the need of renal replacement therapy (RRT) in STEC-HUS patients. ⋯ In a combined model, a joint NGAL/AKIN classification approach improved the predictive accuracy for need of RRT over either marker alone. The combined categorical cut-off point defined by NGAL ≥ 330 ng/ml and presence of AKI (AKIN ≥ I) on admission correctly identified 20 of 24 patients requiring RRT (odds ratio 20, sensitivity 83%, specificity 80%, negative predictive value 75%, positive predictive value 87%). NGAL may serve as an adjunctive tool to improve risk prediction in patients with STEC-HUS.
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Review Meta Analysis
Benefit-to-harm ratio of thromboprophylaxis for patients undergoing major orthopaedic surgery. A systematic review.
Surgeons consider the benefit-to-harm ratio when making decisions regarding the use of anticoagulant venous thromboembolism (VTE) prophylaxis. We evaluated the benefit-to-harm ratio of the use of newer anticoagulants as thromboprophylaxis in patients undergoing major orthopaedic surgery using the likelihood of being helped or harmed (LHH), and assessed the effects of variation in the definition of major bleeding on the results. A systematic literature search was performed to identify phase II and phase III studies that compared regulatory authority-approved newer anticoagulants to the low-molecular-weight heparin enoxaparin in patients undergoing major orthopaedic surgery. ⋯ The exclusion of bleeding at surgical site which did not require reoperation shifted the benefit-to-harm ratio in favour of the newer agents. Variations in the definitions of major bleeding may change the benefit-to-harm ratio and subsequently affect its interpretation. Clinical trials should attempt to improve the consistency of major bleeding reporting.
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Randomized Controlled Trial Multicenter Study
Darexaban (YM150) versus enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a randomised phase IIb dose confirmation study (ONYX-3).
This double-blind, double-dummy, randomised, phase IIb study (NCT00902928) evaluated different dosing regimens of darexaban compared with enoxaparin (randomised 1:1:1:1:1 to 15 mg twice daily [bid], 30 mg once daily [qd], 30 mg bid or 60 mg qd or enoxaparin 40 mg qd) in patients undergoing elective total hip arthroplasty. Patients, investigators, pharmacists and sponsor were all blinded to treatment allocation. Darexaban administration started 6-10 hours (h) post-surgery. ⋯ Darexaban was well tolerated, without signs of liver toxicity. In conclusion, darexaban, administered qd or bid, and at total daily doses of 30 mg or 60 mg, appears to be effective for VTE prevention and was well tolerated. Data suggest no significant differences between a once- or twice-daily dosing regimen.
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Multicenter Study Comparative Study
Mortality in vitamin K antagonist-related intracerebral bleeding treated with plasma or 4-factor prothrombin complex concentrate.
Prothrombin complex concentrates (PCC) can rapidly normalise prolonged prothrombin time, induced by vitamin K antagonists (VKA). We conducted a multicentre retrospective study to investigate whether reversal of VKA coagulopathy with 4-factor PCC improves the survival of patients with VKA-related intracerebral haemorrhage as compared to plasma. We included 135 consecutive patients with VKA-related intracerebral haemorrhage treated either with plasma (mainly in Canada) or 4-factor PCC (The Netherlands and Sweden) for the reversal of VKA. ⋯ The unadjusted OR for all-cause 30-day mortality in the PCC group was 0.40 (95% confidence interval, 0.18-0.87; p=0.021) compared to the plasma group. After adjusting for the haematoma volume, bleeding localisation and age, the effect of PCC on mortality became non-significant. In conclusion, treatment with 4-factor PCC for VKA reversal in patients with intracerebral haemorrhage does not seem to reduce the 30-day all-cause mortality compared to plasma.
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Newer oral anticoagulants offer several advantages over traditional agents (e.g. warfarin), but they are still associated with a bleeding risk and currently there is no validated reversal treatment for them. While there is little support for the use of fresh frozen plasma, and limited data available on the effects of activated recombinant factor VII, preclinical data suggest that prothrombin complex concentrates (PCCs) may have potential in this setting. PCCs are currently used to successfully reverse warfarin-induced anticoagulation; however, clinical evidence for their use with new oral anticoagulants is lacking, with most of the available data coming from preclinical animal studies. ⋯ Although there have been encouraging results, care must be taken in generalising findings from animal models and nonbleeding human subjects to the situation in bleeding patients. Ultimately, more evidence supporting anticoagulation reversal for new anticoagulants is needed, particularly regarding the treatment of bleeding in human patients in a clinical setting. According to the current evidence, use of PCCs may be considered a reasonable approach in dire clinical situations; however, a consensus has not yet been reached regarding PCC use or dosing, due to lack of clinical data.