Direct Oral anticoagulant reversal agents for life-threatening bleeding
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DOAC |
MOA |
Reversal Agent |
Mechanism of Action |
Dosage |
|
Factor Xa Inhibitors Apixaban, Rivaroxaban, Edoxaban |
Factor Xa is a key enzyme that converts prothrombin into thrombin, which then converts fibrinogen into fibrin. |
Andexanet Alfa |
Recombinant modified human Factor Xa decoy that binds Factor Xa inhibitors, reversing their anticoagulant effect. |
High Dose: 800 mg IV bolus at 30 mg/min, followed by 8 mg/min infusion for up to 120 minutes Low Dose: 400 mg IV bolus, then 4 mg/min infusion for 120 min |
|
Prothrombin Complex Concentrate (PCC, Kcentra) |
Provides clotting factors II, VII, IX, and X, bypassing the anticoagulant effect of Factor Xa inhibitors. |
50 units/kg IV (maximum dose 5000 units) |
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Dabigatran (Pradaxa) |
Directly inhibits free and clot-bound thrombin (Factor IIa) |
Idarucizumab |
Monoclonal antibody fragment that binds dabigatran, neutralizing its anticoagulant effect. |
5 grams IV (two consecutive 2.5 g infusions over 10–20 minutes) |
|
Fondaparinux |
Selective Factor Xa inhibition (SQ) |
No specific antidote (supportive ± PCC or rFVIIa) |
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All DOACs |
Activated Charcoal |
Absorbs the anticoagulant in the gastrointestinal tract to reduce systemic absorption. |
Administer if last DOAC dose was ingested within 2–4 hours |
Apixaban (Eliquis), Rivaroxaban (Xarelto), Edoxaban (Savaysa, Lixiana), Fondaparinux (Arixtra), Dabigatran (Pradaxa).
Heparins and Coumadin: Reversal for Life-Threatening Bleeding
Anti-coagulant | MOA | Reversal Agent | Mechanism of Action | Dosage |
Warfarin | Inhibits vitamin K epoxide reductase, preventing synthesis of vitamin K-dependent factors (II, VII, IX, and X) | Vitamin K (phytonadione)
| Vitamin K repletes substrate for gamma-carboxylation of clotting factors. | Major Bleed: • Vitamin K 5–10 mg IV (infuse slowly). • 4-F PCC 50 units/kg IV (max ~5000 units).
Non-major bleed: • Lower doses of Vitamin K (e.g., 1–2.5 mg IV/PO) as needed based on INR. |
+ 4-F PCC (Kcentra) | 4-F PCC provides exogenous clotting factors (II, VII, IX, X) | |||
Unfractionated Heparin (UFH) | Binds AT, inhibiting primarily IIa & Xa | Protamine | Forms a stable complex (salt) with heparin, neutralizing its anticoagulant activity | – 1 mg protamine neutralizes ~100 units of heparin given in the previous 2–3 hours – Usual max single dose ~50 mg – Administer slowly (e.g., over 10 minutes) to reduce hypotension or bradycardia risk |
LMWH (Enoxaparin) | Binds antithrombin, preferentially inhibiting Factor Xa (and to a lesser extent Factor IIa) | Protamine | Forms ionic complexes with LMWH (though only partially effective) | – If LMWH given <8 hours prior: 1 mg protamine per 1 mg of enoxaparin
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