How to reverse anticoagulation in a Jehovah's Witness (JW) patient with coagulopathy?

From the Guidelines

For Jehovah's Witnesses requiring anticoagulation reversal, the most effective approach is to use non-blood product options, such as idarucizumab (Praxbind) 5g IV for dabigatran or andexanet alfa (Andexxa) for factor Xa inhibitors, as recommended by the 2024 ACC/AHA/ACCP/HRS guideline 1.

Key Considerations

• The choice of reversal agent depends on the specific anticoagulant used, with idarucizumab being the preferred option for dabigatran and andexanet alfa for factor Xa inhibitors.
• Vitamin K (5-10mg IV or oral) and prothrombin complex concentrates (PCCs) that are free of plasma, such as Kcentra, can be used for warfarin reversal, with dosing based on INR.
• Other supportive measures, including tranexamic acid, desmopressin, and recombinant factor VIIa, can be employed in severe cases or when specific reversal agents are not available.

Reversal Agents

• Idarucizumab: 5g IV, with an onset of action within 5 minutes and a duration of action of 12-24 hours 1.
• Andexanet alfa: 400-800mg IV bolus, followed by an infusion of 4-8mg/min, with an onset of action within 2 minutes and a duration of action of 2 hours 1.

Patient-Specific Factors

• Individual Jehovah's Witnesses may have varying acceptance of certain blood-derived products, and their specific preferences should be discussed and documented beforehand.
• Consultation with hematology is recommended for complex cases, and mechanical hemostasis, minimally invasive procedures, and cell salvage techniques should be employed when possible.

Clinical Decision-Making

• The decision to reverse anticoagulation should be individualized, taking into account the balance between thrombosis risk and potential complications of bleeding, as outlined in the 2020 ACC expert consensus decision pathway 1.
• The choice of reversal agent and the timing of restart of anticoagulation should be guided by the severity of the bleeding, the likelihood of controlling the bleeding, and the clinical indication for continued 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)]. Reversal of Anticoagulant Effect An agent to reverse the anti-factor Xa activity of rivaroxaban is available. Because of high plasma protein binding, rivaroxaban is not dialyzable [see Clinical Pharmacology (12. 3)] . Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of rivaroxaban. Use of procoagulant reversal agents, such as prothrombin complex concentrate (PCC), activated prothrombin complex concentrate or recombinant factor VIIa, may be considered but has not been evaluated in clinical efficacy and safety studies

Reversing Anticoagulation:

• For patients taking apixaban or rivaroxaban, an agent to reverse the anti-factor Xa activity is available 2 3.
• Prothrombin complex concentrate (PCC), activated prothrombin complex concentrate, or recombinant factor VIIa may be considered, but have not been evaluated in clinical studies.
• Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of apixaban or rivaroxaban.
• Hemodialysis does not appear to have a substantial impact on apixaban exposure, and rivaroxaban is not dialyzable due to high plasma protein binding.
• There is no specific guidance on reversing anticoagulation in Jehovah's Witness patients, and the decision to use a reversal agent should be made on a case-by-case basis, considering the individual patient's risk of bleeding and thrombosis.

From the Research

Reversing Anticoagulation in Jehovah's Witnesses

• Jehovah's Witnesses do not accept allogeneic blood transfusion due to Bible-based religious reasons, but they may accept nonblood alternatives 4.
• In the case of anticoagulation reversal, the primary goal is to support hemostasis while minimizing the risk of post-reversal thrombosis 5.
• Available guidelines recommend administration of vitamin K and 4-factor prothrombin complex concentrates (4F-PCCs) for vitamin K antagonist (VKA) reversal in patients with life-threatening bleeding 5.
• For direct oral anticoagulant (DOAC) reversal, specific reversal agents are recommended, but off-label use of PCCs may be considered when specific reversal agents are unavailable 5, 6.

Management of Bleeding with Non-Vitamin K Antagonist Oral Anticoagulants

• Nonspecific hemostatic agents such as prothrombin complex concentrates and recombinant factor VIIa can be used to reverse the effect of non-vitamin K antagonist oral anticoagulants (NOACs) 6.
• More specific reversing agents include idarucizumab for reversing dabigatran, andexanet alfa, and ciraparantag for reversing anti-Xa NOACs 6.
• Laboratory measurement of the anticoagulant effect of NOACs is best accomplished with specialized assays, although some coagulation tests can provide useful information 6.

Pharmacologic Interventions for Reversing Oral Anticoagulants

• Exogenous vitamin K (phytonadione) may be used in combination with another intervention, such as fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), or activated PCC (aPCC), to reverse the anticoagulant effects of warfarin 7.
• Clotting factor concentrates may be useful for reversing the effects of target-specific oral anticoagulants, but limited efficacy and safety data are available to support their use 7.
• The risks and benefits associated with these products need to be weighed before their use for reversal of dabigatran, rivaroxaban, or apixaban 7.