ArticleThrombosis and haemostasis2013
Reversal of rivaroxaban anticoagulation by haemostatic agents in rats and primates.
Article in Thrombosis and haemostasis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 125 citations in OpenAlex.
- Efficacy of prothrombin complex concentrate in the management of oral factor Xa inhibitors associated major bleed assessed by ISTH and ANNEXA-4 criteria.Journal of thrombosis and thrombolysis · 2022Article
- The impact of prothrombin complex concentrates when treating DOAC-associated bleeding: a review.International journal of emergency medicine · 2018Review
- [Hemorrhage under direct oral anticoagulants : Occurrence and treatment in intensive care patients].Medizinische Klinik, Intensivmedizin und Notfallmedizin · 2018Review
- Reversal Agents: What We Have and What We Can Expect.The Journal of innovations in cardiac rhythm management · 2018Review
- Pharmacological reversal of the direct oral anticoagulants-A comprehensive review of the literature.Research and practice in thrombosis and haemostasis · 2018Review
- Safety of 4-factor prothrombin complex concentrate (4F-PCC) for emergent reversal of factor Xa inhibitors.Journal of intensive care · 2018Article
- Initial anticoagulation in patients with pulmonary embolism: thrombolysis, unfractionated heparin, LMWH, fondaparinux, or DOACs?British journal of clinical pharmacology · 2017Review
- The Reversal of Direct Oral Anticoagulants in Animal Models.Shock (Augusta, Ga.) · 2017Review
- The reversal effect of prothrombin complex concentrate (PCC), activated PCC and recombinant activated factor VII in apixaban-treated patients in vitro.Research and practice in thrombosis and haemostasis · 2017Article
- The reversal effect of prothrombin complex concentrate (PCC), activated PCC and recombinant activated factor VII against anticoagulation of Xa inhibitor.Thrombosis journal · 2017Article
- Ex vivo reversal of effects of rivaroxaban evaluated using thromboelastometry and thrombin generation assay.British journal of anaesthesia · 2016Article
- How we treat bleeding associated with direct oral anticoagulants.Blood transfusion = Trasfusione del sangue · 2016Review
- In vitro reversal of supratherapeutic rivaroxaban levels with coagulation factor concentrates.Blood transfusion = Trasfusione del sangue · 2016Article
- A rapid pro-hemostatic approach to overcome direct oral anticoagulants.Nature medicine · 2016Article
- Who, when, and how to reverse non-vitamin K oral anticoagulants.Journal of thrombosis and thrombolysis · 2016Review
- Factor Xa inhibitors: a novel therapeutic class for the treatment of nonvalvular atrial fibrillation.Therapeutic advances in cardiovascular disease · 2016Review
- Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage: A Statement for Healthcare Professionals from the Neurocritical Care Society and Society of Critical Care Medicine.Neurocritical care · 2016Review
- Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment.Journal of thrombosis and thrombolysis · 2016Review
- Monitoring the Effects and Antidotes of the Non-vitamin K Oral Anticoagulants.Arrhythmia & electrophysiology review · 2015Article
- Reversal Strategies for Intracranial Hemorrhages in Patients Taking Oral Factor Xa Inhibitors.Hospital pharmacy · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rivaroxaban is an oral, direct factor Xa inhibitor for the management of thromboembolic disorders. Despite its short half-life, the ability to reverse rivaroxaban anticoagulation could be beneficial in life-threatening emergencies. The potential of prothrombin complex concentrate (PCC; Beriplex®), activated PCC (aPCC; FEIBA®) or recombinant activated factor VII (rFVIIa; NovoSeven®) to reverse rivaroxaban in rats and baboons was investigated. Anaesthetised rats pre-treated with intravenous rivaroxaban (2 mg/kg) received intravenous rFVIIa (100/400 μg/kg), PCC (25/50 U/kg) or aPCC (50/100 U/kg) after initiation of bleeding. Clotting times and bleeding times (BTs) were recorded. Rivaroxaban was administered as an intravenous 0.6 mg/kg bolus followed by continuous 0.6 mg/kg/hour infusion in baboons. Animals received intravenous aPCC 50 U/kg (2 U/kg/minute) or rFVIIa 210 μg/kg. BT and clotting parameters were measured. In rats pretreated with high-dose rivaroxaban, PCC 50 U/kg, aPCC 100 U/kg and rFVIIa 400 μg/kg significantly reduced BT vs rivaroxaban alone (5.4 ± 1.4-fold to 1.5 ± 0.4-fold [p<0.05]; 3.0 ± 0.4-fold to 1.4 ± 0.1-fold [p<0.001]; and 3.5 ± 0.7-fold to 1.7 ± 0.2-fold [p<0.01] vs baseline, respectively). In baboons pre-infused with rivaroxaban and then given aPCC, BT increased by 2.0 ± 0.2-fold and aPCC returned BT to baseline for the duration of its infusion. rFVIIa reduced BT from 2.5 ± 0.3-fold over baseline to 1.7 ± 0.3-fold over baseline. Prolongation of prothrombin time was reduced by PCC, aPCC and rFVIIa in both species. Rivaroxaban reduced thrombin-antithrombin levels; application of PCC and aPCC, but not rFVIIa, increased these levels. In conclusion, PCC, aPCC or rFVIIa have the potential to reverse the anticoagulant and anti-haemostatic effects of rivaroxaban.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.