Trial reportThrombosis and haemostasis2012
Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers.
Trial report in Thrombosis and haemostasis, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02185027 (Observatory of Invasive Procedures and Bleeding in Patients Treated With New Oral Anticoagulants), which is not on this map. Cited by 140 papers, 7 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Observatory of Invasive Procedures and Bleeding in Patients Treated With New Oral Anticoagulants
Who cites it
140 citing papers in PubMed, 7 syntheses or guidelines pooled it, 502 citations in OpenAlex.
- Prothrombin complex concentrate in major bleeding associated with DOACs; an updated systematic review and meta-analysis.Journal of thrombosis and thrombolysis · 2021Pooled it
- Management of direct factor Xa inhibitor-related major bleeding with prothrombin complex concentrate: a meta-analysis.Blood advances · 2019Pooled it
- The Reversal of Bleeding Caused by New Oral Anticoagulants (NOACs): A Systematic Review and Meta-Analysis.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis · 2018Pooled it
- Prothrombin complex concentrate for reversal of vitamin K antagonist treatment in bleeding and non-bleeding patients.The Cochrane database of systematic reviews · 2015Pooled it
- Pooled it
- Clinical review: Clinical management of new oral anticoagulants: a structured review with emphasis on the reversal of bleeding complications.Critical care (London, England) · 2013Pooled it
- Management of bleeding and coagulopathy following major trauma: an updated European guideline.Critical care (London, England) · 2013Pooled it
- Trial
- Effect of PCC on Thrombin Generation among Patients on Factor Xa Inhibitors with Major Bleeding or Needing Urgent Surgery (GAUGE): Design and Rationale.TH open : companion journal to thrombosis and haemostasis · 2023Article
- Anticoagulation and bleeding in the cancer patient.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022Article
- Fresh Frozen Plasma in Cases of Acute Upper Gastrointestinal Bleeding Does Not Improve Outcomes.Frontiers in medicine · 2022Article
- Extensive spontaneous cervical epidural hematoma due to oral anticoagulant (dabigatran) successfully treated with reversal agent idarucizumab alone.Surgical neurology international · 2022Article
- Low-dose versus standard-dose four-factor prothrombin complex concentrate for factor-Xa inhibitor reversal in spontaneous and traumatic intracranial hemorrhage.Pharmacotherapy · 2021Article
- Review
- Prothrombin complex concentrates for DOAC-associated bleeding, global coagulation assays, and assessments of clinical hemostasis: How to gauge the impact?Research and practice in thrombosis and haemostasis · 2020Article
- A review of oral anticoagulants, old and new, in major bleeding and the need for urgent surgery.Trends in cardiovascular medicine · 2020Review
- Reversal of rivaroxaban anticoagulant effect by prothrombin complex concentrates: which dose is sufficient to restore normal thrombin generation?Thrombosis journal · 2020Article
- Coagulopathy reversal in intracerebral haemorrhage.Stroke and vascular neurology · 2020Review
- Andexanet Response.Annals of emergency medicine · 2019Article
- Current status of oral anticoagulant reversal strategies: a review.Annals of translational medicine · 2019Review
80 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on byReverse engineering for new oral anticoagulants: non-specific reversal agents and the anticoagulant activity of dabigatran and rivaroxaban.2012 · Crackowski, Jean Luc [corrected to Cracowski, Jean Luc]
- Commented on by
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The new anticoagulants dabigatran and rivaroxaban can be responsible for haemorrhagic complications. As for any anticoagulant, bleeding management is challenging. We aimed to test the effect of all putative haemostatic agents on the anticoagulant activity of these new drugs using thrombin generation tests. In an ex vivo study, 10 healthy white male subjects were randomised to receive rivaroxaban (20 mg) or dabigatran (150 mg) in one oral administration. After a two weeks washout period, they received the other anticoagulant. Venous blood samples were collected just before drug administration (H0) and 2 hours thereafter. Reversal of anticoagulation was tested in vitro using prothrombin complex concentrate (PCC), rFVIIa or FEIBA® at various concentrations. Rivaroxaban affects quantitative and kinetic parameters, including the endogenous thrombin potential (ETP-AUC and more pronouncedly the thrombin peak), the lag-time and time to peak. PCC strongly corrected ETP-AUC, whereas rFVIIa only modified the kinetic parameters. FEIBA corrected all parameters. Dabigatran specially affects the kinetics of thrombin generation with prolonged lag-time and time to peak. Although PCC increased ETP-AUC, only rFVIIa and FEIBA corrected the altered lag-time. For both anticoagulants, lower doses of FEIBA, corresponding to a quarter to half the dose usually used, have potential reversal profile of interest. In conclusion, some non-specific reversal agents appear to be able to reverse the anticoagulant activity of rivaroxaban or dabigatran. However, clinical evaluation is needed regarding haemorrhagic situations, and a meticulous risk-benefit evaluation regarding their use in this context is required.
Indexed as
Identifiers
What OpenQuestion holds
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.