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Anticoagulant Reversal – Treatment Options and Safety

The Anesthesia Guide » Topics » Anticoagulant Reversal – Treatment Options and Safety

Author:
Kai Knudsen



Updated:
26 August, 2025

This section provides a brief overview of how to reverse the effects of various anticoagulants (NOACs) and thromboprophylactic medications. Reversal can be performed urgently before surgery or in cases of abnormal bleeding following treatment with these anticoagulants (NOACs).

Content:
  1. Classification of various anticoagulants
  2. Apixaban (Eliquis®) – Reversal
  3. Clopidogrel (Plavix®) – Reversal
  4. Dabigatran (Pradaxa®) – Reversal
  5. Dalteparin (Fragmin®) – Reversal
  6. Edoxaban (Lixiana®) – Reversal
  7. Enoxaparin (Klexane®) – Reversal
  8. Fondaparinux (Arixtra®) – Reversal
  9. Heparin (Heparin®) – Reversal
  10. Prasugrel (Efient®) – Reversal
  11. Rivaroxaban (Xarelto®) – Reversal
  12. Ticagrelor (Brilique®) – Reversal
  13. Warfarin (Waran®) – Reversal

Classification of various anticoagulants

Apixaban (Eliquis®) – Reversal

There is no specific antidote. The half-life is about 12 hours.

Consider treatment with:

A) Prothrombin complex concentrate (PCC); Coagulation Factor II + IX (Ocplex®) maximum dose up to 50 units/kg IV; should not exceed 5000 units (in single doses). If ingested less than 15 hours ago, give 2000 IU PCC. If 15-24 hours since the Eliquis dose, give 1500 IU PCC.

B) Andexanet alfa (Ondexxya®) may be considered if available. Andexanet alfa is administered as an intravenous bolus dose at a rate of approximately 30 mg/min over 15 minutes (low dose) or 30 minutes (high dose), followed by administration of a continuous infusion at a rate of 4 mg/min (low dose) or 8 mg/min (high dose) over 120 minutes.

C) Tranexamic acid (Cyklokapron®) 25 mg/kg IV

D) Desmopressin (Octostim Injection®) 0.3 mcg/kg SC or IV; should be limited to 2 IV doses (12 -24 hours apart)

E) Activated charcoal can be given if Eliquis intake was within the last 2 hours. Dosage: 100 g PO/through a tube.

FFP: not recommended

RFVIIa (Novoseven®): not recommended

Clopidogrel (Plavix®) – Reversal

Clopidogrel (Plavix) is a prodrug, and one of its metabolites is a platelet aggregation inhibitor that can prevent platelet activation and aggregation. Since the binding is irreversible, exposed platelets are affected for the remainder of their lifespan (approximately 7-10 days), and recovery of normal platelet function occurs at a rate corresponding to platelet turnover.

There is no known antidote for clopidogrel.

Consider treatment with:

  • Platelet transfusion 2-4 units.
  • Desmopressin (Octostim Injection®) 0.3 mcg/kg SC or IV; should be limited to 2 IV doses (12 -24 hours apart)
  • Tranexamic acid (Cyklokapron®) 25 mg/kg IV

Dabigatran (Pradaxa®) – Reversal

Pradaxa has a half-life of 12-14 hours but can be longer.

Reversed with: Idarucizumab (Praxbind®)

Dosage: 5.0 g IV in total dose (given in two separate doses of 2.5 g with 15 minutes apart)

Alternatives that may be considered if Praxbind is not available:

  • Prothrombin complex concentrate (PCC); Coagulation Factor II + IX (Ocplex®) maximum dose up to 50 units/kg IV; should not exceed 5000 units (in single doses). If ingested less than 15 hours ago, give 2000 IU PCC. If 15-24 hours since the Eliquis dose, give 1500 IU PCC.
  • Hemodialysis
  • Activated charcoal; 100 g PO/through a tube if the intake time is less than 2 hours
  • Tranexamic acid (Cyklokapron®) 25 mg/kg IV
  • 4F-aPCC (FEIBA® – prothrombin complex, activated) 50 units/kg IV; should not exceed 5000 units (in individual doses)
  • Desmopressin (Octostim Injection®) 0.3 mcg/kg SC or IV; should be limited to 2 IV doses (12 -24 hours apart)
  • FFP: not recommended
  • RFVIIa (Novoseven®): not recommended

Dalteparin (Fragmin®) – Reversal

Dalteparin sodium is the sodium salt of low molecular weight heparin (LMWH). Dalteparin’s antithrombotic effect is due to its ability to enhance antithrombin’s inhibition of Factor Xa and thrombin, thereby reducing blood clot formation. The effect of dalteparin can be monitored by analyzing plasma levels of anti-Xa/ml .

Prophylactic dose is not reversed. In case of overdose, consider attempting reversal with:

Protamine sulfate if the dalteparin dose was given within 3-4 hours.

Protamine sulfate is strongly basic and binds acidic heparin to form a stable inactive complex.

Dosage: 1 mg per 100 units of dalteparin administered; should not exceed 50 mg in total.

Max infusion rate – 5 mg/min.

Check Anti-Xa after the initial dose and then after 2-8 hours

Edoxaban (Lixiana®) – Reversal

The half-life is about 12 hours.

Reversed with: There is no specific antidote. 

Otherwise, consider treatment with:

A) Prothrombin complex; Coagulation Factor II + IX (Ocplex®) max dose is 50 units/kg IV; should not exceed 5000 units (in single doses)

  • If <15 hours since the ingested dose, give 2000 IU PCC (Ocplex).
  • If 15-24 hours since the dose, give 1500 IU PCC.

B) Andexanet alfa (Ondexxya®) may be considered if available. Andexanet alfa is administered as an intravenous bolus dose at a rate of approximately 30 mg/min over 15 minutes (low dose) or 30 minutes (high dose), followed by administration of a continuous infusion at a rate of 4 mg/min (low dose) or 8 mg/min (high dose) over 120 minutes.

C) Tranexamic acid (Cyklokapron®) 25 mg/kg IV

D) Desmopressin (Octostim Injection®) 0.3 mcg/kg SC or IV; should be limited to 2 IV doses (12 -24 hours apart)

E) Activated charcoal can be given if Lixiana intake was within the last 2 hours. Dosage: 100 g PO/through a tube.

FFP: not recommended

RFVIIa (Novoseven®): not recommended

Enoxaparin (Klexane®) – Reversal

Reversed with: Protamine sulfate

Dosage:

  • 1 mg of Protamine per mg of enoxaparin if the last injection was within 8 hours.
  • 0.5 mg of Protamine per mg of enoxaparin if the last injection was more than 8 hours ago.
  • 0.5 mg of Protamine per mg of enoxaparin if bleeding persists 4 hours after the first dose.
  • Single doses should not exceed 50 mg.

Maximum infusion rate – 5 mg/min.

Fondaparinux (Arixtra®) – Reversal

There is no known antidote to fondaparinux, but there is some experience in administering Prothrombin Complex (PCC), Coagulation Factor II + IX (Ocplex®). One may also consider NovoSeven 90-100 µg/kg and/or Feiba 20-30 IE/kg.

Dosage: PCC max 50 units/kg; should not exceed 5000 units. Administer only one dose. If Arixtra was taken less than 15 hours ago, a practical guideline may be to start with 2000 IU PCC. If 15-24 hours have passed since the Arixtra dose, start with 1500 IU PCC.

Reversed with: Prothrombin complex, Coagulation Factor II + IX (Ocplex®).

Dosage: 50 units/kg; should not exceed 5000 units. Administer only one dose.

Heparin (Heparin®) – Reversal

Reversed with: Protamine sulfate

Protamine sulfate is strongly basic and binds acidic heparin to form a stable inactive complex.

Dosage: 1 mg per 100 units of heparin administered; should not exceed 50 mg in total.

Max infusion rate – 5 mg/min.

Check a-PTT 5-15 minutes after the initial dose and then after 2-8 hours

Prasugrel (Efient®) – Reversal

Prasugrel is an inhibitor of platelet activation and aggregation by its active metabolite binding irreversibly to the P2Y12 group on platelets’ adenosine diphosphate (ADP) receptors.

There is no known antidote for prasugrel.

Consider treatment with:

  • Platelet transfusion 2-4 units.
  • Desmopressin (Octostim Injection®) 0.3 mcg/kg SC or IV; should be limited to 2 IV doses (12 -24 hours apart)
  • Tranexamic acid (Cyklokapron®) 25 mg/kg IV

Rivaroxaban (Xarelto®) – Reversal

Rivaroxaban (Xarelto) has a half-life of approximately 5–13 hours.

Reversed with:

  • Prothrombin complex concentrate (PCC); coagulation factor II + IX (Ocplex®) can be given in a dose of up to 50 units/kg IV but should never exceed 5000 units (in single doses).
  • With an INR between 2-4, start with a dose of 25 U/kg, max 2500 U.
  • With an INR between 4-6, start with a dose of 35 U/kg, max 3500 U.
  • With an INR over 6, start with a dose of 50 U/kg, max 5000 U.
  • If Xarelto was taken less than 15 hours prior, a practical guideline could be to start with 2000 U PCC. If 15-24 hours have passed since the intake of Xarelto, start with 1500 U PCC. Measure new INR for follow-up after 30 minutes.
  • Andexanet alfa (Ondexxya®) may be considered if available. Andexanet alfa is administered as an intravenous bolus dose at a rate of approximately 30 mg/min over 15 minutes (low dose) or 30 minutes (high dose), followed by administration of a continuous infusion at a rate of 4 mg/min (low dose) or 8 mg/min (high dose) over 120 minutes.
  • Tranexamic acid 25 mg/kg (Cyklokapron®) IV.
  • Desmopressin 0.3 mcg/kg (Octostim Injection®) SC or IV; should be limited to 2 IV doses (12 -24 hours apart).
  • 4F-aPCC (FEIBA® – prothrombin complex, activated) 50 units/kg IV; should not exceed 5000 units (in individual doses).
  • FFP: not recommended.
  • RFVIIa (Novoseven®): not recommended.
  • Activated charcoal can be given if Xarelto was ingested within 2 hours.

Dosage: 100 g PO/through a tube;

Ticagrelor (Brilique®) – Reversal

Ticagrelor belongs to the chemical class cyclopentyltriazolopyrimidines (CPTP) and is a selective ADP receptor antagonist that can prevent platelet activation and aggregation.

There is no known antidote for ticagrelor.

Consider treatment with:

  • Platelet transfusion 2-4 units.
  • Desmopressin (Octostim Injection®) 0.3 mcg/kg SC or IV; should be limited to 2 IV doses (12 -24 hours apart)
  • Tranexamic acid (Cyklokapron®) 25 mg/kg IV

Warfarin (Waran®) – Reversal

The active ingredient warfarin inhibits the blood’s ability to coagulate and thus prevents the formation of thrombi in blood vessels. Waran contains warfarin in the form of warfarin sodium and is a synthetic anticoagulant of the coumarin type. Warfarin induces an anticoagulant effect by blocking the vitamin K cycle. Vitamin K is necessary to complete the synthesis of coagulation factors II, VII, IX, and X in the liver.

Reversed with: Prothrombin complex, Coagulation Factor II + IX (medication name Ocplex®)

Ocplex Dosage:

  • If INR is 2 to < 4: give 25 units/kg; the dose should not exceed 2500 units
  • If INR is 4 to 6: give 35 units/kg; do not exceed 3500 units
  • If INR > 6: give 50 units/kg; do not exceed 5000 units
  • If only one dose is given OR if Ocplex is not available, also administer:

Fresh frozen plasma: 10-20 ml/kg plus

Vitamin K (Konakion): 5-10 mg in infusion (administered slowly intravenously) with either Ocplex or FFP

Repeat INR 30-60 minutes after administering the antidote

 

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