{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:42:04Z","timestamp":1782978124922,"version":"3.54.5"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Broxmeyer Fellowship in Clinical Thrombosis"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>The advent of direct-acting oral anticoagulants (DOACs) has transformed the care of patients requiring prevention and treatment for thrombotic disease. Many randomized clinical trials have demonstrated the efficacy and safety of these agents and their comparative advantages over conventional anticoagulants such as vitamin K antagonists (VKAs). While historically clinicians and patients raised questions about the reversal of DOAC-associated bleeding, federal approval in recent years of targeted DOAC reversal agents, along with adjunctive modalities, has given clinicians reliable pharmacologic options. Yet, optimal reversal strategies for bleeding at specific anatomic locations and in specific clinical scenarios remains uncertain. We present here a narrative review of the literature on the reversal of DOAC-associated bleeding or for urgent procedures. The totality of the reversal literature synthesized here yields several clear conclusions: (1) targeted DOAC reversal with specific agents demonstrates superior efficacy for both bleeding and urgent surgical indications when compared to the use of non-specific agents, such as prothrombin complex concentrates (PCCs); (2) at the same time, high-quality data suggest potentially increased thrombotic risks, particularly for ischemic stroke, when using the specific targeted agent andexanet; (3) in all cases of life-threatening bleeding, timely reversal is of the essence; (4) in particular, there is growing consensus that DOAC-associated intracranial hemorrhage (ICH) should be reversed promptly, with a goal door-to-reversal time of 60 min; (5) future research will focus on optimizing clinical pathways for reversal to address \u201ccalls to action\u201d from professional groups on this critical topic.<\/jats:p>","DOI":"10.3390\/jcm14031013","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T10:09:52Z","timestamp":1738750192000},"page":"1013","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Reversal of Direct Oral Anticoagulants (DOACs) for Critical Bleeding or Urgent Procedures"],"prefix":"10.3390","volume":"14","author":[{"given":"Mark","family":"Goldin","sequence":"first","affiliation":[{"name":"Northwell, 2000 Marcus Ave., Suite 300, New Hyde Park, NY 11042-1069, USA"},{"name":"Department of Medicine, Anticoagulation and Clinical Thrombosis Services, Northwell, New Hyde Park, NY 11042-1069, USA"},{"name":"Institute of Health System Science, Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"},{"name":"Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Hempstead, NY 11549, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9524-6238","authenticated-orcid":false,"given":"Nikolaos","family":"Tsaftaridis","sequence":"additional","affiliation":[{"name":"Northwell, 2000 Marcus Ave., Suite 300, New Hyde Park, NY 11042-1069, USA"},{"name":"Department of Medicine, Anticoagulation and Clinical Thrombosis Services, Northwell, New Hyde Park, NY 11042-1069, USA"},{"name":"Institute of Health System Science, Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7716-8990","authenticated-orcid":false,"given":"Jack","family":"Jnani","sequence":"additional","affiliation":[{"name":"Northwell, 2000 Marcus Ave., Suite 300, New Hyde Park, NY 11042-1069, USA"},{"name":"Department of Medicine, Anticoagulation and Clinical Thrombosis Services, Northwell, New Hyde Park, NY 11042-1069, USA"},{"name":"Department of Medicine, North Shore University Hospital, Manhasset, NY 11549, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3175-461X","authenticated-orcid":false,"given":"Alex C.","family":"Spyropoulos","sequence":"additional","affiliation":[{"name":"Northwell, 2000 Marcus Ave., Suite 300, New Hyde Park, NY 11042-1069, USA"},{"name":"Department of Medicine, Anticoagulation and Clinical Thrombosis Services, Northwell, New Hyde Park, NY 11042-1069, USA"},{"name":"Institute of Health System Science, Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"},{"name":"Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Hempstead, NY 11549, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1161\/ATVBAHA.114.304488","article-title":"Thrombosis: A Major Contributor to Global Disease Burden","volume":"34","author":"Raskob","year":"2014","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1016\/j.chest.2021.07.056","article-title":"Executive Summary: Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report","volume":"160","author":"Stevens","year":"2021","journal-title":"Chest"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1182\/bloodadvances.2020001830","article-title":"American Society of Hematology 2020 Guidelines for Management of Venous Thromboembolism: Treatment of Deep Vein Thrombosis and Pulmonary Embolism","volume":"4","author":"Ortel","year":"2020","journal-title":"Blood Adv."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/S0140-6736(13)62343-0","article-title":"Comparison of the Efficacy and Safety of New Oral Anticoagulants with Warfarin in Patients with Atrial Fibrillation: A Meta-Analysis of Randomised Trials","volume":"383","author":"Ruff","year":"2014","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1477-9560-11-21","article-title":"Oral Rivaroxaban versus Standard Therapy for the Treatment of Symptomatic Venous Thromboembolism: A Pooled Analysis of the EINSTEIN-DVT and PE Randomized Studies","volume":"11","author":"Prins","year":"2013","journal-title":"Thromb. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e020904","DOI":"10.1161\/JAHA.121.020904","article-title":"Direct Oral Anticoagulant Adherence of Patients with Atrial Fibrillation Transitioned from Warfarin","volume":"10","author":"Pundi","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1161\/CIRCULATIONAHA.121.056355","article-title":"Direct Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation: Patient-Level Network Meta-Analyses of Randomized Clinical Trials with Interaction Testing by Age and Sex","volume":"145","author":"Carnicelli","year":"2022","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.7326\/M21-1094","article-title":"Long-Term Risk for Major Bleeding During Extended Oral Anticoagulant Therapy for First Unprovoked Venous Thromboembolism: A Systematic Review and Meta-Analysis","volume":"174","author":"Khan","year":"2021","journal-title":"Ann. Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.thromres.2016.01.004","article-title":"Urgent Surgery or Procedures in Patients Taking Dabigatran or Warfarin: Analysis of Perioperative Outcomes from the RE-LY Trial","volume":"139","author":"Douketis","year":"2016","journal-title":"Thromb. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1056\/NEJMoa2313040","article-title":"Andexanet for Factor Xa Inhibitor\u2013Associated Acute Intracerebral Hemorrhage","volume":"390","author":"Connolly","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1161\/CIRCULATIONAHA.121.057844","article-title":"Final Study Report of Andexanet Alfa for Major Bleeding with Factor Xa Inhibitors","volume":"147","author":"Milling","year":"2023","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1177\/17474930241230209","article-title":"Andexanet Alfa versus Non-Specific Treatments for Intracerebral Hemorrhage in Patients Taking Factor Xa Inhibitors\u2014Individual Patient Data Analysis of ANNEXA-4 and TICH-NOAC","volume":"19","author":"Siepen","year":"2024","journal-title":"Int. J. Stroke"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s13054-022-04043-8","article-title":"Andexanet Alfa versus Four-Factor Prothrombin Complex Concentrate for the Reversal of Apixaban- or Rivaroxaban-Associated Intracranial Hemorrhage: A Propensity Score-Overlap Weighted Analysis","volume":"26","author":"Costa","year":"2022","journal-title":"Crit. Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1161\/STROKEAHA.121.034572","article-title":"Hematoma Expansion and Clinical Outcomes in Patients with Factor-Xa Inhibitor\u2013Related Atraumatic Intracerebral Hemorrhage Treated Within the ANNEXA-4 Trial Versus Real-World Usual Care","volume":"53","author":"Huttner","year":"2022","journal-title":"Stroke"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e12655","DOI":"10.1002\/emp2.12655","article-title":"Thirty-Day Mortality with Andexanet Alfa Compared with Prothrombin Complex Concentrate Therapy for Life-Threatening Direct Oral Anticoagulant-Related Bleeding","volume":"3","author":"Cohen","year":"2022","journal-title":"J. Am. Coll. Emerg. Physicians Open"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102192","DOI":"10.1016\/j.rpth.2023.102192","article-title":"Lower Mortality with Andexanet Alfa vs. 4-Factor Prothrombin Complex Concentrate for Factor Xa Inhibitor-Related Major Bleeding in a U.S. Hospital-Based Observational Study","volume":"7","author":"Dobesh","year":"2023","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1136\/emermed-2023-213229","article-title":"Four-Factor Prothrombin Complex Concentrate versus Andexanet Alfa for the Reversal of Traumatic Brain Injuries","volume":"41","author":"Sadek","year":"2024","journal-title":"Emerg. Med. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e209","DOI":"10.1055\/a-2306-0804","article-title":"Clinical Pathways and Outcomes of Andexanet Alfa Administration for the Reversal of Critical Bleeding in Patients on Oral Direct Factor Xa Inhibitors","volume":"8","author":"Goldin","year":"2024","journal-title":"TH Open"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ajem.2022.02.029","article-title":"Andexanet Alfa versus Four-Factor Prothrombin Complex Concentrate for the Reversal of Apixaban- or Rivaroxaban-Associated Intracranial Hemorrhages","volume":"55","author":"Pham","year":"2022","journal-title":"Am. J. Emerg. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s11239-023-02820-y","article-title":"Real-World Clinical Outcomes among US Veterans with Oral Factor Xa Inhibitor\u2013Related Major Bleeding Treated with Andexanet Alfa or 4-Factor Prothrombin Complex Concentrate","volume":"56","author":"Sutton","year":"2023","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ajem.2022.02.036","article-title":"Andexanet Alfa Effectiveness and Safety versus Four-Factor Prothrombin Complex Concentrate (4F-PCC) in Intracranial Hemorrhage While on Apixaban or Rivaroxaban: A Single-Center, Retrospective, Matched Cohort Analysis","volume":"55","author":"Parsels","year":"2022","journal-title":"Am. J. Emerg. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s11239-023-02840-8","article-title":"Deterioration Free Discharge Comparison of Andexanet-Alfa and Prothrombin Complex Concentrates (PCC) for Reversal of Factor Xa Inhibitor Associated Bleeds","volume":"56","author":"Keinath","year":"2023","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s11239-022-02752-z","article-title":"Comparison of 4-Factor Prothrombin Complex Concentrate and Andexanet Alfa for Reversal of Apixaban and Rivaroxaban in the Setting of Intracranial Hemorrhage","volume":"55","author":"Lipski","year":"2022","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1097\/MBC.0000000000001279","article-title":"The Use of Andexanet Alfa vs. 4-Factor Prothrombin Complex Concentrates in the Setting of Life-Threatening Intracranial Hemorrhage","volume":"35","author":"Bacchus","year":"2024","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.japh.2023.11.015","article-title":"Four-Factor Prothrombin Complex Concentrate versus Andexanet Alfa for Direct Oral Anticoagulant Reversal","volume":"64","author":"Koo","year":"2024","journal-title":"J. Am. Pharm. Assoc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s11239-021-02495-3","article-title":"Andexanet Alfa and Four-Factor Prothrombin Complex Concentrate for Reversal of Apixaban and Rivaroxaban in Patients Diagnosed with Intracranial Hemorrhage","volume":"53","author":"Vestal","year":"2022","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1177\/08971900221125516","article-title":"Real-World Reversal of Factor Xa Inhibition in the Setting of Major Life-Threatening Bleeding or Urgent Surgery","volume":"37","author":"Schmidt","year":"2024","journal-title":"J. Pharm. Pract."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"939","DOI":"10.5811\/WESTJEM.60587","article-title":"Treatment of Factor-Xa Inhibitor-Associated Bleeding with Andexanet Alfa or 4 Factor PCC: A Multicenter Feasibility Retrospective Study","volume":"24","author":"Singer","year":"2023","journal-title":"WestJEM"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/s13054-024-05014-x","article-title":"Andexanet Alpha versus Four-Factor Prothrombin Complex Concentrate in DOACs Anticoagulation Reversal: An Updated Systematic Review and Meta-Analysis","volume":"28","author":"Orso","year":"2024","journal-title":"Crit. Care"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e2240145","DOI":"10.1001\/jamanetworkopen.2022.40145","article-title":"Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage","volume":"5","author":"Chaudhary","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1056\/NEJMoa1707278","article-title":"Idarucizumab for Dabigatran Reversal\u2014Full Cohort Analysis","volume":"377","author":"Pollack","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s40256-019-00360-6","article-title":"Real World Outcomes Associated with Idarucizumab: Population-Based Retrospective Cohort Study","volume":"20","author":"Singh","year":"2020","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1161\/CIRCULATIONAHA.113.002283","article-title":"Efficacy and Safety of a 4-Factor Prothrombin Complex Concentrate in Patients on Vitamin K Antagonists Presenting with Major Bleeding: A Randomized, Plasma-Controlled, Phase IIIb Study","volume":"128","author":"Sarode","year":"2013","journal-title":"Circulation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1002\/ana.25134","article-title":"Association of Prothrombin Complex Concentrate Administration and Hematoma Enlargement in Non\u2013Vitamin K Antagonist Oral Anticoagulant\u2013Related Intracerebral Hemorrhage","volume":"83","author":"Gerner","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1182\/blood-2017-05-782060","article-title":"Management of Rivaroxaban- or Apixaban-Associated Major Bleeding with Prothrombin Complex Concentrates: A Cohort Study","volume":"130","author":"Majeed","year":"2017","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1055\/s-0038-1636541","article-title":"Prothrombin Complex Concentrate for Major Bleeding on Factor Xa Inhibitors: A Prospective Cohort Study","volume":"118","author":"Schulman","year":"2018","journal-title":"Thromb. Haemost."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1161\/CIRCULATIONAHA.120.045769","article-title":"Factor Xa Inhibitor-Related Intracranial Hemorrhage: Results from a Multicenter, Observational Cohort Receiving Prothrombin Complex Concentrates","volume":"141","author":"Panos","year":"2020","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hays, W.B., Billups, K., Nicholson, J., Bailey, A.M., Gregory, H., Weeda, E.R., and Weant, K.A. (2024). 3-Factor Prothrombin Complex Concentrate versus 4-Factor Prothrombin Complex Concentrate for the Reversal of Oral Factor Xa Inhibitors. J. Thromb. Thrombolysis.","DOI":"10.1007\/s11239-024-03052-4"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1161\/STROKEAHA.123.042866","article-title":"Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial","volume":"54","author":"Polymeris","year":"2023","journal-title":"Stroke"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1007\/s40265-018-0940-4","article-title":"Andexanet Alfa: First Global Approval","volume":"78","author":"Heo","year":"2018","journal-title":"Drugs"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lu, G., Pine, P., Leeds, J.M., DeGuzman, F., Pratikhya, P., Lin, J., Malinowski, J., Hollenbach, S.J., Curnutte, J.T., and Conley, P.B. (2018). Andexanet Alfa Effectively Reverses Edoxaban Anticoagulation Effects and Associated Bleeding in a Rabbit Acute Hemorrhage Model. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0195122"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1182\/blood.V124.21.4269.4269","article-title":"A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial Demonstrating Reversal of Edoxaban-Induced Anticoagulation in Healthy Subjects By Andexanet Alfa (PRT064445), a Universal Antidote for Factor Xa (fXa) Inhibitors","volume":"124","author":"Crowther","year":"2014","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"A1469","DOI":"10.1097\/01.ccm.0000457952.01186.20","article-title":"455: Reversal of Factor XA Inhibitors-Induced Anticoagulation in Healthy Subjects by Andexanet Alfa","volume":"42","author":"Crowther","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3554","DOI":"10.1182\/blood-2012-11-468207","article-title":"A Specific Antidote for Dabigatran: Functional and Structural Characterization","volume":"121","author":"Schiele","year":"2013","journal-title":"Blood"},{"key":"ref_45","first-page":"331","article-title":"Update on the Mechanism of Action and Future of Activated Prothrombin Complex Concentrates","volume":"3","author":"Turecek","year":"2004","journal-title":"Curr. Hematol. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ul-Haq, Z., and Madura, J.D. (2015). From Conventional Prodrugs to Prodrugs Designed by Molecular Orbital Methods. Frontiers in Computational Chemistry, Bentham Science Publishers.","DOI":"10.2174\/97816080586481150101"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1080\/21548331.2023.2206270","article-title":"Impact of Perioperative Direct Oral Anticoagulant Assays: A Multicenter Cohort Study","volume":"51","author":"Stretton","year":"2023","journal-title":"Hosp. Pract."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.amjmed.2020.01.002","article-title":"Association of Reversal of Anticoagulation Preoperatively on 30-Day Mortality and Outcomes for Hip Fracture Surgery","volume":"133","author":"Yoo","year":"2020","journal-title":"Am. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.thromres.2022.06.005","article-title":"Management of Urgent Invasive Procedures in Patients Treated with Direct Oral Anticoagulants: An Observational Registry Analysis","volume":"216","author":"Godon","year":"2022","journal-title":"Thromb. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1002\/phar.2727","article-title":"Reversal of Apixaban and Rivaroxaban with Andexanet Alfa Prior to Invasive or Surgical Procedures","volume":"42","author":"Bradshaw","year":"2022","journal-title":"Pharmacotherapy"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e204","DOI":"10.1097\/SLA.0000000000003638","article-title":"Dabigatran Reversal with Idarucizumab in Patients Requiring Urgent Surgery: A Subanalysis of the RE-VERSE AD Study","volume":"274","author":"Levy","year":"2021","journal-title":"Ann. Surg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.thromres.2020.06.044","article-title":"Activated Prothrombin Complex Concentrates for Direct Oral Anticoagulant-Associated Bleeding or Urgent Surgery: Hemostatic and Thrombotic Outcomes","volume":"195","author":"Shaw","year":"2020","journal-title":"Thromb. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1159\/000502173","article-title":"Prothrombin Complex Concentrate before Urgent Surgery in Patients Treated with Rivaroxaban and Apixaban","volume":"143","author":"Barzilai","year":"2020","journal-title":"Acta Haematol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ajem.2018.05.023","article-title":"Safety and Effectiveness of Factor Eight Inhibitor Bypassing Activity for Direct Oral Anticoagulant-Related Hemorrhage Reversal","volume":"37","author":"Engelbart","year":"2019","journal-title":"Am. J. Emerg. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.amjsurg.2020.12.034","article-title":"The AAST Prospective Observational Multicenter Study of the Initial Experience with Reversal of Direct Oral Anticoagulants in Trauma Patients","volume":"222","author":"Emigh","year":"2021","journal-title":"Am. J. Surg."},{"key":"ref_56","unstructured":"Shoamanesh, A., Demchuk, A., and Seiffge, D. (2024, January 7\u20139). Secondary Analyses to Optimize Response to Andexanet from ANNEXa-I. Proceedings of the 2024 International Stroke Conference, Phoenix, AZ, USA."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"127","DOI":"10.2217\/fca-2020-0073","article-title":"Real-World Management of Oral Factor Xa Inhibitor-Related Bleeds with Reversal or Replacement Agents Including Andexanet Alfa and Four-Factor Prothrombin Complex Concentrate: A Multicenter Study","volume":"17","author":"Coleman","year":"2021","journal-title":"Future Cardiol"},{"key":"ref_58","unstructured":"AstraZeneca AB (2024). ANDEXXA [Package Insert], AstraZeneca."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1056\/NEJMoa1814051","article-title":"Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors","volume":"380","author":"Connolly","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1001\/jamaneurol.2024.0221","article-title":"Time to Anticoagulation Reversal and Outcomes After Intracerebral Hemorrhage","volume":"81","author":"Sheth","year":"2024","journal-title":"JAMA Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1161\/STROKEAHA.123.043033","article-title":"Code ICH: A Call to Action","volume":"55","author":"Li","year":"2024","journal-title":"Stroke"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/3\/1013\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:27:26Z","timestamp":1760027246000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/3\/1013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,5]]},"references-count":61,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["jcm14031013"],"URL":"https:\/\/doi.org\/10.3390\/jcm14031013","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,5]]}}}