FACTOR XA,INACTIVATED-ZHZO INJ,LYPHL
Clinical Criteria Summary
General Principles & Supportive Care
- Reversal agents considered ONLY for severe, life-threatening bleeding where potential risk of thromboembolism is deemed less than consequences of continued bleeding.
- DOACs have relatively short half-lives; bleeding often managed by temporarily discontinuing anticoagulant and providing supportive care.
- Supportive care includes: discontinuing anticoagulant, maintaining adequate diuresis, compression, surgical repair, fluid and/or blood replacement, hemodynamic support (hemodialysis for dabigatran).
- Consider activated charcoal for known recent DOAC ingestion within past 2-4 hours.
- Consider presence of other antithrombotic drugs (e.g., antiplatelet agents) and discontinue as appropriate.
- Use reversal agents reserved for patients with known recent exposure to a DOAC.
- Restart anticoagulant therapy as soon as medically appropriate due to elevated risk of thromboembolism.
Idarucizumab (Praxbind) Criteria
- Indication: Reversal of dabigatran in setting of bleeding or emergent surgery/urgent procedures.
- Inclusion Criteria (ALL required):
- Patient taking dabigatran with provider reasonably certain therapeutic anticoagulant levels are present.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed ≥8 hours requiring normal hemostasis.
- Standard measures for bleeding management (e.g., discontinuing anticoagulant, compression, surgical repair, fluid/blood replacement, hemodynamic support) are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Specific for dabigatran only; will not reverse effects of other anticoagulants including Factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban).
- Thromboembolic events reported (4.8% within 30-day follow-up in REVERSE-AD); consider restarting anticoagulant as soon as medically appropriate (dabigatran can be started 24 hours after administration).
- Hypersensitivity reactions reported.
- Hereditary fructose intolerance due to sorbitol excipient (4g per dose) requires consideration of combined metabolic load.
- Re-elevation of coagulation parameters observed in limited patients; safety/effectiveness of repeat doses not established.
4-Factor Prothrombin Complex Concentrate (4F-PCC/KCetra) Criteria
- Indication: DOAC-associated life-threatening bleeding or need for emergent surgery/urgent procedures (Off-label).
- Exclusion Criteria (ANY present = NOT receive):
- Known anaphylactic or severe systemic reaction to 4F-PCC or components (heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III, human albumin).
- Disseminated intravascular coagulation.
- History of heparin-induced thrombocytopenia (contains heparin).
- Inclusion Criteria (ALL required):
- Patient taking a DOAC with provider reasonably certain therapeutic anticoagulant levels are present.
- Specific reversal agent FDA approved for patient’s condition is not readily available.
- Life-threatening or critical site bleeding (e.g., ICH) OR need for truly emergent procedure that cannot be delayed requiring normal hemostasis.
- Standard measures for bleeding management are insufficient.
- Patient’s risk of thromboembolism deemed less than consequences of continued bleeding or delay of procedure/surgery.
- Safety & Considerations:
- Boxed warning for arterial and venous thromboembolic complications; higher thromboembolic events vs plasma in VKA trials, especially with history of thromboembolism.
- Not suitable for patients with thromboembolic events in prior 3 months.
- Hypersensitivity reactions observed.
- Risk of transmitting infection from human blood source.
- No FDA-approved products indicated for reversal of apixaban, rivaroxaban, or edoxaban; use of nonspecific agent such as 4F-PCC may be considered though evidence is limited. If 4F-PCC unavailable, activated PCC (aPCC/FEIBA) may be considered.
Dosing & Administration
- Idarucizumab: Single dose 5 gm (2 vials x 2.5 gm). Administered IV as 2 consecutive infusions or bolus injection. Requires refrigeration.
- 4F-PCC: Doses vary: single dose 25-50 units/kg or fixed dose 2,000 units IV. Dosing calculated based on quantity of factor IX in product. Administered by IV infusion at rate up to 8.4 ml/min (~210 units/min). Supplied in 500 or 1000 unit vials requiring reconstitution; store at 2-25°C.