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      Clinical protocols for oral anticoagulant reversal during high risk of bleeding for emergency surgical and nonsurgical settings: a narrative review

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          Abstract

          Background and objectives

          Oral anticoagulants prevent thromboembolic events but expose patients to a significant risk of bleeding due to the treatment itself, after trauma, or during surgery. Any physician working in the emergency department or involved in the perioperative care of a patient should be aware of the best reversal approach according to the type of drug and the patient’s clinical condition. This paper presents a concise review and proposes clinical protocols for the reversal of oral anticoagulants in emergency settings, such as bleeding or surgery.

          Contents

          The authors searched for relevant studies in PubMed, LILACS, and the Cochrane Library database and identified 82 articles published up to September 2020 to generate a review and algorithms as clinical protocols for practical use. Hemodynamic status and the implementation of general supportive measures should be the first approach under emergency conditions. The drug type, dose, time of last intake, and laboratory evaluations of anticoagulant activity and renal function provide an estimation of drug clearance and should be taken into consideration. The reversal agents for vitamin K antagonists are 4-factor prothrombin complex concentrate and vitamin K, followed by fresh frozen plasma as a second-line treatment. Direct oral anticoagulants have specific reversal agents, such as andexanet alfa and idarucizumab, but are not widely available. Another possibility in this situation, but with less evidence, is prothrombin complex concentrates.

          Conclusion

          The present algorithms propose a tool to help healthcare providers in the best decision making for patients under emergency conditions.

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          Most cited references106

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          Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

          The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of spontaneous intracerebral hemorrhage.
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            Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

            VTE is a serious, but decreasing complication following major orthopedic surgery. This guideline focuses on optimal prophylaxis to reduce postoperative pulmonary embolism and DVT. The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. In patients undergoing major orthopedic surgery, we recommend the use of one of the following rather than no antithrombotic prophylaxis: low-molecular-weight heparin; fondaparinux; dabigatran, apixaban, rivaroxaban (total hip arthroplasty or total knee arthroplasty but not hip fracture surgery); low-dose unfractionated heparin; adjusted-dose vitamin K antagonist; aspirin (all Grade 1B); or an intermittent pneumatic compression device (IPCD) (Grade 1C) for a minimum of 10 to 14 days. We suggest the use of low-molecular-weight heparin in preference to the other agents we have recommended as alternatives (Grade 2C/2B), and in patients receiving pharmacologic prophylaxis, we suggest adding an IPCD during the hospital stay (Grade 2C). We suggest extending thromboprophylaxis for up to 35 days (Grade 2B). In patients at increased bleeding risk, we suggest an IPCD or no prophylaxis (Grade 2C). In patients who decline injections, we recommend using apixaban or dabigatran (all Grade 1B). We suggest against using inferior vena cava filter placement for primary prevention in patients with contraindications to both pharmacologic and mechanical thromboprophylaxis (Grade 2C). We recommend against Doppler (or duplex) ultrasonography screening before hospital discharge (Grade 1B). For patients with isolated lower-extremity injuries requiring leg immobilization, we suggest no thromboprophylaxis (Grade 2B). For patients undergoing knee arthroscopy without a history of VTE, we suggest no thromboprophylaxis (Grade 2B). Optimal strategies for thromboprophylaxis after major orthopedic surgery include pharmacologic and mechanical approaches.
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              Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial.

              Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients. This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919. 10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group; relative risk 0.91, 95% CI 0.85-0.97; p=0.0035). The risk of death due to bleeding was significantly reduced (489 [4.9%] vs 574 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p=0.0077). Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients. UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation. Copyright 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Braz J Anesthesiol
                Braz J Anesthesiol
                Brazilian Journal of Anesthesiology
                Elsevier
                0104-0014
                2352-2291
                19 April 2021
                Jul-Aug 2021
                19 April 2021
                : 71
                : 4
                : 429-442
                Affiliations
                [a ]Hospital São Lucas Copacabana, Departamento de Anestesia, Rio de Janeiro, RJ, Brazil
                [b ]Instituto Nacional de Cardiologia, Rio de Janeiro, RJ, Brazil
                [c ]Centro de Pesquisas Oncológicas (CEPON), Departamento de Anestesia, Florianópolis, SC, Brazil
                [d ]Clínica de Anestesiologia, Departamento de Anestesia, Salvador, BA, Brazil
                [e ]Hospital Israelita Albert Einstein, Centro de Oncologia e Hematologia, Setor de Hematologia e Coagulação, Departamento de Patologia Clínica, São Paulo, SP, Brazil
                Author notes
                [* ]Corresponding author. cgalhardo@ 123456uol.com.br
                Article
                S0104-0014(21)00137-8
                10.1016/j.bjane.2021.03.007
                9373671
                33887335
                d5054236-3772-4316-9f00-5fa237a862ab
                © 2021 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 11 January 2020
                : 13 March 2021
                Categories
                Narragtive Review

                reversal of oral anticoagulants,warfarin,non-vitamin k antagonists,direct oral anticoagulants,prothrombin complex concentrates,idarucizumab,andexanet alfa

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