- Clinical science
Anticoagulant reversal is a critical step in the management of patients with life-threatening bleeding who are taking an anticoagulant. The reversal agents indicated depend on the specific anticoagulant taken by the patient. The risk of thromboembolic events is increased by most reversal agents. For this reason, their use should be limited to cases of serious or life-threatening bleeding. All patients who undergo anticoagulation reversal should be monitored closely.
|Drug class||Drug names||Monitoring parameters ||Half-life ||Reversal agents |
|Oral vitamin K antagonists|| |
|Heparins||Unfractionated heparin|| |
|Low molecular weight heparin|| || |
|Synthetic pentasaccharide factor Xa inhibitors|| || |
|Direct oral anticoagulants||Direct thrombin inhibitors|| || |
|Direct Xa inhibitors|
Nonspecific reversal agents like 4-factor prothrombin complex concentrate (PCC), activated PCC, recombinant activated factor VII, thrombocyte concentrates, and fresh frozen plasma have procoagulatory effects! Before these drugs are administered, the increased risk of thrombosis should be carefully weighed against the risk of ongoing bleeding. 
The treatment strategy depends on whether the patient is symptomatic and if there is serious or life-threatening bleeding present. 
Active hemorrhage (regardless of INR) 
- Stop warfarin.
- Administer IV vitamin K. PLUS 4-factor prothrombin complex concentrate (PCC)
- Monitor INR every 6 hours until warfarin has been fully reversed (INR ≤ 1.1)
Asymptomatic patient with elevated INR
|Serum INR||Recommended management |
|INR greater than therapeutic range but < 5.0|
|INR ≥ 5 but < 10|| |
|INR ≥ 10|
General principles 
- Stop heparin.
- Protamine is the mainstay of heparin reversal but has variable effects depending on the type of heparin. 
- Check platelets if the patient is on unfractionated or LMWH and has serious bleeding to rule out heparin-induced thrombocytopenia.
Reversal of unfractionated heparin and LMWH 
Protamine dosing for unfractionated heparin 
|Time since last heparin dose||Recommended IV protamine dose|
|< 30 minutes|
|> 120 minutes|
|Time since enoxaparin dose||Recommended IV protamine dose|
|< 8 hours|
|> 12 hours|| |
- Tinzaparin or dalteparin
The total dose of protamine should never exceed 50 mg.
Reversal of fondaparinux
Both aPCC and recombinant activated factor VII increase the risk of thrombosis.
Reversal of dabigatran 
- Stop dabigatran.
- Administer idarucizumab.
- If idarucizumab is not available, administer aPCC.
- Consider hemodialysis.
Reversal of factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban, betrixaban) 
- Stop the factor Xa inhibitor.
- Administer one of the following:
- High-dose regimen of andexanet alfa indicated if:
- Low dose regimen of andexanet alfa indicated if:
- 3-factor or 4-factor PCC
- Andexanet alfa
PCC and aPCC increase the risk of thrombosis.
- Stop the anticoagulant.
- Provide hemodynamic support.
- Consider local and interventional hemostatic methods.
- Check labs
- Obtain patient consent for blood transfusion.
- Transfuse if necessary (see transfusion).
- Consider imaging, depending on the suspected site of bleeding.
- Give anticoagulant reversal agent, if available (see overview of anticoagulant reversal agents).