Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan;23(1):64-69.
doi: 10.2450/BloodTransfus.993. Epub 2025 Jan 22.

Reversal of oral anticoagulation in emergency conditions

Anna Falanga  1   2   3 , Chiara Ambaglio  1 , Luca Barcella  1
Affiliations

Reversal of oral anticoagulation in emergency conditions

Anna Falanga et al. Blood Transfus. 2025 Jan.
No abstract available

PubMed Disclaimer

Conflict of interest statement

The Authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Oral anticoagulant drugs and their specific antidotes
Vitamin K antagonists (VKAs), such as warfarin, acenocoumarol, and phenprocoumon, deplete the active form of vitamin K by inhibiting the enzyme vitamin K epoxide reductase, impairing the synthesis of fully active vitamin K-dependent coagulation factors II, VII, IX, and X. The specific antidote for VKAs is Vitamin K. The direct oral anticoagulants (DOACs) factor Xa inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban) inhibit both free and clot-bound factor Xa, as well as prothrombinase activity, while dabigatran is a potent, synthetic, reversible, non-peptide inhibitor of thrombin (FIIa). Specific antidotes for DOACs include idarucizumab for dabigatran, and andexanet alfa for factor Xa inhibitors. TF: tissue factor.
Figure 2
Figure 2. Reversal of vitamin K antagonist
A dose of 10 mg of vitamin K, diluted in 100 mL saline solution, is administered intravenously (IV) over 30 minutes. This treatment facilitates the synthesis of active prothrombin complex factors, reducing prothrombin time-international normalized ratio (PT-INR) within 4 to 6 hours, with complete normalization achieved within 24 hours. Due to the latency of vitamin K action, in cases of major bleeding, it is necessary to start the restitution of factors by administering prothrombin complex concentrates (PCC). The baseline INR determines the recommended dose of four-factor-PCC (4F-PCC) for patients needing urgent reversal of VKAs. The dosing guidelines are as follows: administer 50 IU/kg for an INR of 6, 35 IU/kg for an INR between 4 and 6, and 25 IU/kg for an INR between 2 and 4.
Figure 3
Figure 3. Antidotes for anti-IIa (Idarucizumab) and anti-Xa (Andexanet-α)
A) Idarucizumab is a humanized monoclonal antibody that binds dabigatran with an affinity 350-fold higher than thrombin. The recommended dose of Idarucizumab is 5 g as a fixed IV infusion of two aliquots of 2.5 g. B) Andexanet-alfa is a recombinant protein with a similar structure to endogenous FXa that binds FXa inhibitors but lacks enzymatic activity. For patients taking low doses of apixaban or rivaroxaban, andexanet should be administered as an initial intravenous (IV) bolus of 400 mg at a target rate of 30 mg/min. This should be followed by an IV infusion of 4 mg/min for up to 120 minutes. For patients taking standard doses, a higher dose of andexanet is recommended. This should consist of an initial IV bolus of 800 mg at a target rate of 30 mg/min, followed by an IV infusion of 8 mg/min for up to 120 minutes.
See this image and copyright information in PMC

References

    1. Ortel TL, Neumann I, Ageno W, Beyth R, Clark NP, Cuker A, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv. 2020;4:4693–4738. doi: 10.1182/bloodadvances.2020001830. - DOI - PMC - PubMed
    1. Van Gelder IC, Rienstra M, Bunting KV, Casado-Arroyo R, Caso V, Crijns HJGM, et al. ESC Scientific Document Group. 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS) Eur Heart J. 2024;45:3314–3414. doi: 10.1093/eurheartj/ehae176. - DOI - PubMed
    1. Stevens SM, Woller SC, Baumann Kreuziger L, Bounameaux H, Doerschug K, Geersing GJ, et al. Executive summary: antithrombotic therapy for VTE disease: second update of the CHEST Guideline and Expert Panel Report. Chest. 2021;160:2247–2259. doi: 10.1016/j.chest.2021.07.056. - DOI - PubMed
    1. AIFA Italian Medicines Agency [internet] AIFA publishes the National Report “The Use of Medicines in Italy” (Year 2022) [Accessed on 21/11/2024]. Available at: https://www.aifa.gov.it/en/-/aifa-pubblica-rapporto-osmed-2022ci-in-italia.
    1. Linz D, Gawalko M, Betz K, Hendriks JM, Lip GYH, Vinter N, et al. Atrial fibrillation: epidemiology, screening and digital health. Lancet Reg Health Eur. 2024;37:100786. doi: 10.1016/j.lanepe.2023.100786. - DOI - PMC - PubMed

LinkOut - more resources