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Correspondence to Author: Rosane Rezende De Souza Giuliani¹, Felipe Santos Teixeira Martiniano²,Nicole Mioto Medeiros³,Lorenzo Francesco Giuliani⁴⁴, Ana Laura Munerato Zoega Marotti⁵,Fernanda Tranquillini⁶,Rafaela Gonçalves Bueno¹,Dieudonné Massoma Lembe⁶,Thiago Augusto Rochetti Bezerra ^6,7, Leocadia Felix De Araujo⁸. 

1. Graduated in Medicine Medicine. Head of the Hematology Service at the Portuguese Beneficent Society of Santos, São Paulo, Brazil. Professor of Hematology at the University of Ribeirão Preto (UNAERP), São Paulo, Brazil.
2. Graduated in Medicine. Resident Physician in Internal Medicine, Beneficência Portuguesa Hospital of Santos, São Paulo, Brazil.
3. Graduated in Medicine from the University of Vale do Sapucaí (Univás), Minas Gerais, Brazil. Hematology and Hemotherapy at the Amaral Carvalho Hospital, Jaú, São Paulo, Brazil. Physician at the Portuguese Beneficência Hospital in Santos and at the University of Ribeirão Preto (UNAERP), São Paulo, Brazil.
4. Graduated in Medicine. Resident physician. Specialist in Anesthesia, Resuscitation, Intensive Care, and Pain at the University of Rome “La Sapienza,” Rome, Italy.
5. Graduated in Medicine from the University of Marília (Unimar), São Paulo, Brazil. Residency in Clinical Medicine at Ana Costa Hospital, Santos, São Paulo, Brazil. Residency in Hematology and Hemotherapy at the Marília School of Medicine (Famema), São Paulo, Brazil. Works at Ana Costa Hospital, Beneficência Portuguesa Hospital in Santos, Angiocorpore, and Guilherme Álvaro Hospital, Santos, São Paulo, Brazil.
6. Academic in Medicine from the University of Ribeirão Preto, Guarujá campus.
7. Ph.D of Medical Sciences, Ribeirão Preto Medical School, University of São Paulo.
8. Graduated in Medicine from the Federal University of Fronteira Sul, Passo Fundo Campus, Rio Grande do Sul, Brazil

DOI: 10.52338/tajoh.2025.5083

Abstract:

Direct oral anticoagulants (DOACs) have revolutionized the prevention and treatment of non-valvular atrial fibrillation and venous thrombosis, offering similar or superior efficacy to warfarin with a lower risk of intracranial hemorrhage. However, the occurrence of major bleeding, particularly in the gastrointestinal tract and intracranial, remains a significant clinical challenge, reinforcing the need for effective reversal strategies Objective:To evaluate the scientific literature on the efficacy, safety, and reversibility of DOACs, highlighting specific antidotes (idarucizumab and andexanet alfa) and non-specific alternatives, and to discuss their clinical and regulatory impact.
Methodology:A systematic review was conducted following the PRISMA 2020 recommendations, including randomized clinical trials, metaanalyses, observational studies, and guidelines published between 2010 and 2025. The PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus databases were searched using descriptors related to DOACs, efficacy, safety, and reversal.
Results: The literature confirms that DOACs significantly reduce thromboembolic events, intracranial hemorrhage, and mortality compared to warfarin, although they present a variable risk of gastrointestinal bleeding among the different agents. Idarucizumab demonstrated immediate and sustained reversal of dabigatran, with high rates of hemostasis and clinical safety. Andexanet alfa showed hemostatic efficacy in severe bleeding due to factor Xa inhibitors, but was associated with a higher incidence of thrombotic events, with no proven benefit in mortality or functional disability in the ANNEXA-I study. Alternatives such as prothrombin complex concentrate (4F-PCC), hemodialysis (for dabigatran), and activated charcoal in recent ingestion remain relevant. Evidence also suggests that off-label doses increase the risk of complications, reinforcing the need for individualized adjustments
Conclusion:DOACs represent a significant therapeutic advance, but their reversal remains a field of debate and development. Specific antidotes are already a clinical reality, albeit with limitations. Individualized strategies, institutional protocols, and future research on universal antidotes, such as ciraparantag, are essential to optimize safety and reduce morbidity and mortality in anticoagulated patients.

Keywords: Direct oral anticoagulants; Reversal; Idarucizumab; Andexanet alfa; Safety; Efficacy; Hemorrhage.

Citation:

Dr.Thiago Augusto Rochetti Bezerra, Systematic Review on New Anticoagulants and Their Reversibility, Studies on The Safety, Efficacy, and Antidotes of Direct Oral Anticoagulants (Doacs). The American Journal of Hematology 2025.