Thrombosis and haemostasis
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Randomized Controlled Trial Multicenter Study
Extended anticoagulation with apixaban reduces hospitalisations in patients with venous thromboembolism. An analysis of the AMPLIFY-EXT trial.
Treatment with apixaban versus placebo for 12 months significantly reduced symptomatic recurrent venous thromboembolism (VTE) or all-cause death without increasing the rate of major bleeding in the AMPLIFY-EXT trial. This analysis examined the effects of apixaban versus placebo on the rate of all-cause hospitalisations, time to first hospitalisation, and predictors of first hospitalisation in patients with VTE enrolled in AMPLIFY-EXT. Treatment with apixaban 2.5 mg and 5 mg twice daily significantly reduced the rate of all-cause hospitalisations versus placebo (hazard ratio [95% confidence interval], 0.64 [0.43, 0.95]; p=0.026 and 0.54 [0.36, 0.82]; p=0.004, respectively). ⋯ Median length of hospital stay during the first hospitalisation was longer for placebo than for apixaban 2.5 mg or 5 mg twice daily (7.0, 5.0, and 4.5 days, respectively). Treatment with apixaban was a significant predictor of lower rates of hospitalisations versus placebo, and severe/moderate renal impairment was a significant predictor of an increased rate. This study supports extended use of apixaban for reducing all-cause hospitalisations and extending time to first hospitalisation in patients with VTE enrolled in AMPLIFY-EXT (www.clinicaltrials.gov registration: #NCT00633893).
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Randomized Controlled Trial
The MARINER trial of rivaroxaban after hospital discharge for medical patients at high risk of VTE. Design, rationale, and clinical implications.
Hospital-associated venous thromboembolism (VTE) is a leading cause of premature death and disability worldwide. Evidence-based guidelines recommend that anticoagulant thromboprophylaxis be given to hospitalised medical patients at risk of VTE, but suggest against routine use of thromboprophylaxis beyond the hospital stay. The MARINER study is a randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of thromboprophylaxis using rivaroxaban, begun at hospital discharge and continued for 45 days, for preventing symptomatic VTE in high-risk medical patients. ⋯ A blinded clinical events committee adjudicates all suspected outcome events. The sample size is event-driven with an estimated total of 8,000 patients to acquire 161 primary outcome events. Study design features that distinguish MARINER from previous and ongoing thromboprophylaxis trials in medically ill patients are: (i) use of a validated risk assessment model (IMPROVE VTE) and D-dimer determination for identifying eligible patients at high risk of VTE, (ii) randomisation at the time of hospital discharge, (iii) a 45-day treatment period and (iv) restriction of the primary efficacy outcome to symptomatic VTE events.
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Randomized Controlled Trial Multicenter Study
Effect of high or low protamine dosing on postoperative bleeding following heparin anticoagulation in cardiac surgery. A randomised clinical trial.
While experimental data state that protamine exerts intrinsic anticoagulation effects, protamine is still frequently overdosed for heparin neutralisation during cardiac surgery with cardiopulmonary bypass (CPB). Since comparative studies are lacking, we assessed the influence of two protamine-to-heparin dosing ratios on perioperative haemostasis and bleeding, and hypothesised that protamine overdosing impairs the coagulation status following cardiac surgery. In this open-label, multicentre, single-blinded, randomised controlled trial, patients undergoing on-pump coronary artery bypass graft surgery were assigned to a low (0.8; n=49) or high (1.3; n=47) protamine-to-heparin dosing group. ⋯ Postoperative blood loss was increased in the high dosing ratio group (615 ml; 95 % CI 500-830 ml vs 470 ml; 95 % CI 420-530 ml; p=0.021) when compared to the low dosing group, respectively. More patients in the high dosing group received fresh frozen plasma (11 % vs 0 %; p=0.02) and platelet concentrate (21 % vs 6 %; p=0.04) compared to the low dosing group. Our study confirms in vitro data that abundant protamine dosing is associated with increased postoperative blood loss and higher transfusion rates in cardiac surgery.
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Randomized Controlled Trial Multicenter Study
Apixaban and dalteparin in active malignancy associated venous thromboembolism. The ADAM VTE Trial.
Currently, low molecular weight heparin (LMWH) is the guideline endorsed treatment of patients with cancer associated venous thromboembolism (VTE). While apixaban is approved for the treatment of acute VTE, there are limited data supporting its use in cancer patients. The rationale and design of this investigator initiated Phase IV, multicenter, randomized, open label, superiority trial assessing the safety of apixaban versus dalteparin for cancer associated VTE is provided (ADAM-VTE; NCT02585713). ⋯ Stratification factors used for randomization include cancer stage and cancer specific risk of venous thromboembolism using the Khorana score. Participating centers are chosen from the Academic and Community Cancer Research United (ACCRU) consortium comprised of 90 oncology practices in the United States and Canada. Based on the hypothesis to be tested, we anticipate that these trial results will provide evidence supporting apixaban as an effective treatment of cancer associated VTE at lower rates of major bleeding compared to LMWH.
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Coronavirus disease 2019 vaccine ChAdOx1 nCov-19 may rarely lead to vaccine-induced thrombotic thrombocytopenia (VITT). Antibody-mediated, platelet factor 4 (PF4)-dependent platelet activation appears to resemble a key mechanism in VITT, partially comparable to heparin-induced thrombocytopenia. The use of PF4/heparin immunoassays has been proposed as part of a diagnostic approach, but their sensitivity has not been established. ⋯ It seems feasible to establish functional antibody testing for the confirmation of VITT. For the initial screening of suspected VITT cases, PaGIA, LFA, and CLIA are useless when applied as single tests. Only ELISA-based PF4/heparin immunoassays are sensitive enough to be incorporated in the diagnostic workup. However, a combination of a positive ELISA and a negative CLIA may be useful to identify VITT antibodies in the absence of confirmatory functional assays.