What are the guidelines for reversing anticoagulation (Anti-Coagulation) therapy?

From the Guidelines

Anticoagulation reversal should be guided by the specific anticoagulant involved and the urgency of the situation, with idarucizumab (5g IV) recommended for dabigatran reversal and andexanet alfa for factor Xa inhibitors like apixaban and rivaroxaban, as per the most recent guidelines 1.

Key Considerations

• The choice of reversal agent depends on the type of anticoagulant used, with different agents having specific reversal strategies.
• Idarucizumab is the recommended reversal agent for dabigatran, with a dose of 5g IV, as supported by studies such as the REVERSE AD study 1.
• Andexanet alfa is used for factor Xa inhibitors like apixaban and rivaroxaban, with doses based on timing and dose of the anticoagulant, as outlined in the 2023 WSES guidelines 1.

Reversal Strategies

• For warfarin reversal, vitamin K (5-10mg IV or oral) should be administered along with prothrombin complex concentrate (PCC) at 25-50 units/kg for serious bleeding.
• For heparin reversal, protamine sulfate is administered at 1mg per 100 units of heparin given in the previous 2-3 hours.
• In emergency situations without specific reversal agents, supportive measures include fresh frozen plasma, PCC, activated PCC, or recombinant factor VIIa.

Clinical Context

• The clinical context, including bleeding severity, time since last anticoagulant dose, and the patient's renal and hepatic function, should guide the reversal approach, as emphasized in the 2020 ACC expert consensus decision pathway 1.
• Blood product support with platelets (for counts <50,000/μL) and red blood cells should be provided as needed.

Evidence Base

• The recommendations are based on the most recent and highest quality studies, including the 2023 WSES guidelines 1 and the 2020 ACC expert consensus decision pathway 1.
• The use of idarucizumab and andexanet alfa is supported by studies such as the REVERSE AD study 1 and the ANNEXA-4 study, which demonstrated the efficacy and safety of these agents in reversing anticoagulation.

From the FDA Drug Label

Reversal of Anticoagulant Effect An agent to reverse the anti-factor Xa activity of apixaban is available The pharmacodynamic effect of apixaban tablets can be expected to persist for at least 24 hours after the last dose, i.e., for about two drug half-lives. Prothrombin complex concentrate (PCC), activated prothrombin complex concentrate or recombinant factor VIIa may be considered, but have not been evaluated in clinical studies [see Clinical Pharmacology (12. 2)].

Anticoagulation Reversal Guidelines:

• An agent to reverse the anti-factor Xa activity of apixaban is available.
• Prothrombin complex concentrate (PCC), activated prothrombin complex concentrate, or recombinant factor VIIa may be considered for reversal.
• These agents have not been evaluated in clinical studies.
• The pharmacodynamic effect of apixaban can be expected to persist for at least 24 hours after the last dose.
• Monitoring for the anticoagulation effect of apixaban using a clotting test (PT, INR, or aPTT) or anti-factor Xa (FXa) activity is not useful and not recommended when PCCs are used. 2

From the Research

Anticoagulation Reversal Guidelines

• The decision to reverse anticoagulation should weigh the benefit-risk ratio of supporting hemostasis versus post-reversal thrombosis 3
• For warfarin reversal, exogenous vitamin K (phytonadione) may be used in combination with another, shorter-acting intervention, such as fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), recombinant factor VIIa, or activated PCC (aPCC) 4
• Clotting factor concentrates are more effective than FFP alone for warfarin reversal 4
• For direct oral anticoagulants (DOACs), specific reversal agents are available, such as idarucizumab for dabigatran and andexanet alfa for factor Xa inhibitors 5, 6, 7
• Prothrombin complex concentrates may be used for DOAC reversal when specific reversal agents are unavailable 5, 3
• Vitamin K and fresh frozen plasma should not be used to reverse DOACs 5

Reversal Strategies

• The choice of reversal strategy depends on the International Normalized Ratio, presence of bleeding, and need for and timing of surgery 4
• Idarucizumab has been approved for dabigatran reversal, and andexanet alfa has been approved for reversal of oral factor Xa inhibitors 5, 6
• Ciraparantag is being investigated in clinical trials for reversal of all DOACs and other anticoagulants 5
• Aripazine has shown promising results to reverse the effects of low-molecular-weight heparin, fondaparinux, and direct oral anticoagulants, but is still in the developmental phase 6

Clinical Scenarios

• Reversal of anticoagulation may be required in patients with life-threatening bleeding, bleeding into a closed space or organ, persistent bleeding despite local haemostatic measures, and need for urgent interventions and/or interventions that carry a high risk for bleeding 7
• Reversal agents may be helpful in patients with major bleeding or those requiring urgent surgery 7
• The emergency department is recommended as an appropriate location for reversal agents 7