Major bleeding on an anticoagulant (adults)
Life-threatening, critical-organ or uncontrolled bleeding. Adults only: for children, get paediatric haematology advice.
All Pathways
Hematology & OncologyEmergency
Anticoagulant Reversal for Major Bleeding (Warfarin, DOAC, Heparin)
Anticoagulant Reversal for Major Bleeding (Warfarin, DOAC, Heparin): Major bleeding on an anticoagulant (adults) → All patients: resuscitate and stop th...
Pathway Overview
14 steps
Algorithm Steps
14 total
01Start 02Action All patients: resuscitate and stop the anticoagulant
Start at once, alongside reversal.
- Stop the anticoagulant. Record the drug, dose and time of the last dose
- Bloods: FBC, INR, APTT, thrombin time, fibrinogen, creatinine (CrCl), group and hold
- Anti-Xa or dabigatran level if available; do not delay reversal for it
- Massive bleeding: activate the major haemorrhage protocol
- Platelets if count <50 × 10^9/L (ICH: threshold up to 100 × 10^9/L). Antiplatelet drug alone (ICH or GI bleed): do not give platelets unless surgery is planned
- Local measures (pressure, surgery, endoscopy, IR). Keep temperature, ionised calcium and pH normal
03Decision Where is the bleeding?
Site care runs alongside reversal. Reversal steps follow.
- Intracranial
04Warning Intracranial bleed: reverse without delay
Reverse at once (next steps). Urgent neurosurgery review. ICU or stroke unit. Low platelets: transfuse at a threshold up to 100 × 10^9/L. On an antiplatelet drug with a normal count: no platelet transfusion unless surgery is planned.
- Give the reversal agent at once; do not wait for levels
- Target SBP about 140 mmHg; do not go below 130 mmHg
- Repeat CT if the patient gets worse
05Warning Before PCC or reversal: check for harm
Adults only (children: paediatric haematology advice). Reversal and PCC raise the risk of thrombosis.
- Known HIT: do not give Beriplex (it contains heparin). Get urgent haematology advice. Warfarin: vitamin K 5-10 mg IV plus FFP
- DIC: give PCC only after the consumptive state has stopped. Treat the cause; urgent haematology advice
- Thrombosis, MI or stroke in the last 3 months, or mechanical valve: high thrombotic risk; reverse only for major bleeding
06Decision Which anticoagulant? Is it still active?
Reverse only if the drug is likely still active (time of last dose, CrCl, drug level or clotting test). DOAC level >50 ng/mL: reverse. Do not wait for a level.
- Warfarin
07Action Warfarin: vitamin K and 4F-PCC (Beriplex)
Omit warfarin. Check INR now. Dose by INR and bleeding severity.
- INR ≥1.5 with life-threatening or critical-organ bleeding: vitamin K 5-10 mg IV and 4F-PCC 50 IU/kg IV
- INR 1.5-1.9: consider a 4F-PCC dose below 50 IU/kg
- INR ≥2.0 with significant (not life-threatening) bleeding: vitamin K 5-10 mg IV and 4F-PCC 25-50 IU/kg IV
- Dose on weight up to 100 kg (max 5000 IU). Rate max 3 IU/kg/min and not above 210 IU/min
- FFP is not needed with 4F-PCC
- Recheck INR about 30 min after PCC. Repeat PCC dose not recommended; get haematology advice
08Action Reassess bleeding and clotting tests
Check that bleeding and coagulopathy are controlled.
- Repeat INR, APTT or drug level after reversal
- Ongoing bleeding: get haematology advice before a repeat dose
- Watch for thrombosis after reversal
- Plan when to restart the anticoagulant; balance bleeding and clot risk
09Outcome Bleeding controlled
Plan anticoagulant restart by indication, with haematology or the treating team.
- Dabigatran
10Action Dabigatran: idarucizumab (Praxbind) 5 g IV
Give if dabigatran is likely still active: level >50 ng/mL, or no level yet (judge by last dose). Effect lasts longer if CrCl <50 mL/min.
- Idarucizumab 5 g IV (2 vials of 2.5 g/50 mL): 2 infusions of 5-10 min each, or bolus
- Recheck clotting tests: levels can rise again up to 24 h later
- Second 5 g dose only if bleeding recurs with prolonged clotting times
- No idarucizumab: 4F-PCC 50 IU/kg IV (max 5000 IU; off-label)
- Haemodialysis removes about 50-60% over 4 h; consider if idarucizumab is not available
- Keep urine output up: dabigatran is cleared by the kidneys
- Path rejoins step 08Shared downstream outcome
- Xa inhibitor
11Action Apixaban, rivaroxaban or edoxaban: 4F-PCC
Give if the drug is likely still active: drug-specific anti-Xa level >50 ng/mL, or no level yet (judge by last dose and CrCl).
- 4F-PCC (Beriplex) 25-50 IU/kg IV (max 5000 IU) or 2000 IU fixed dose (off-label)
- Andexanet alfa: not on the ARTG; withdrawn in the US. Where licensed (EU), use only per local protocol
- Activated charcoal if the last dose was within 6-8 h and the airway is safe
- Haemodialysis does not remove these drugs. Vitamin K and protamine do not work
- Path rejoins step 08Shared downstream outcome
- Heparin, LMWH, other or unknown
12Action Heparin, LMWH, fondaparinux or unknown agent
Unfractionated heparin, enoxaparin or dalteparin: protamine. Fondaparinux or other LMWH: haematology advice.
- UFH: protamine 1 mg per 100 units of heparin given in the last 2-3 h; slow IV over 10 min; max 50 mg per dose (10 mg/mL)
- Protamine: anaphylaxis risk with fish allergy, prior protamine or NPH insulin, or vasectomy
- Enoxaparin in the last 8 h: protamine 1 mg per 1 mg (max 50 mg); 8-12 h: 0.5 mg per 1 mg. Partial reversal only
- Dalteparin: protamine 1 mg per 100 IU of dalteparin given (max 50 mg). APTT still long at 2-4 h: 0.5 mg per 100 IU. Partial reversal only
- Fondaparinux: no specific reversal agent; get haematology advice
- Unknown agent: check INR, APTT, thrombin time and anti-Xa level; treat by result
- Path rejoins step 08Shared downstream outcome
- GI
13Action GI bleed: endoscopy; no routine TXA
Gastroenterology review. Endoscopy within 24 h, sooner if unstable.
- Upper GI bleed: IV PPI (for example pantoprazole 80 mg IV) before endoscopy
- Red cells if Hb <70 g/L (<80 g/L with cardiovascular disease), unless massive bleeding
- Do not give tranexamic acid routinely in GI bleeding
- Antiplatelet drug alone is not a reason for platelet transfusion
- Path rejoins step 05Shared downstream outcome
- Other
14Action Other major bleed (muscle, retroperitoneal, trauma)
Find and control the source.
- CT to find the source
- Surgery or IR (embolisation) as needed
- Trauma: tranexamic acid within 3 h of injury, per major haemorrhage protocol
- Limb bleed: watch for compartment syndrome
- Path rejoins step 05Shared downstream outcome
Guideline Source
Reversal of direct oral anticoagulants: guidance from the SSC of the ISTH (Levy JH et al., J Thromb Haemost 2024;22(10):2889-2899)
Clinical Safety Information
Clinical Decision Support — Not a Substitute for Clinical Judgment
Individual patient factors may require deviation from these recommendations.
Known Limitations
- Andexanet alfa (ISTH 2024 first choice for Xa inhibitors) is not on the ARTG and is withdrawn in the US; where licensed (EU), use only per local protocol. 4F-PCC for DOAC reversal is off-label
- Adults only; children need paediatric haematology advice
- Drug levels (anti-Xa, dabigatran) may not be available quickly
- Does not cover antiplatelet reversal or perioperative (non-bleeding) reversal
Contraindicated Populations
childrenknown_HIT_for_heparin_containing_PCC
Applicable Regions
AUNZUSEUGlobal
AU: 4F-PCC (Beriplex AU) is on the ARTG and replaces Prothrombinex-VF plus FFP for warfarin reversal. Andexanet alfa is not on the ARTG. Idarucizumab (Praxbind) is on the ARTG.
EU: Andexanet alfa (Ondexxya) has conditional EU authorisation; use per local protocol, noting the higher thrombotic event rate in ANNEXA-I.
US: Andexanet alfa (Andexxa) was withdrawn from the US market. Idarucizumab and 4F-PCC are available.
Version 2Next review: 2027-09-30
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Frequently Asked Questions
What is the Anticoagulant Reversal for Major Bleeding (Warfarin, DOAC, Heparin)?
The Anticoagulant Reversal for Major Bleeding (Warfarin, DOAC, Heparin) is a emergency clinical algorithm for Hematology & Oncology. It provides a structured decision tree to guide clinical decision-making, based on Reversal of direct oral anticoagulants: guidance from the SSC of the ISTH (Levy JH et al., J Thromb Haemost 2024;22(10):2889-2899).
What guideline is the Anticoagulant Reversal for Major Bleeding (Warfarin, DOAC, Heparin) based on?
This algorithm is based on Reversal of direct oral anticoagulants: guidance from the SSC of the ISTH (Levy JH et al., J Thromb Haemost 2024;22(10):2889-2899) (DOI: 10.1016/j.jtha.2024.07.009).
What are the limitations of the Anticoagulant Reversal for Major Bleeding (Warfarin, DOAC, Heparin)?
Known limitations include: Andexanet alfa (ISTH 2024 first choice for Xa inhibitors) is not on the ARTG and is withdrawn in the US; where licensed (EU), use only per local protocol. 4F-PCC for DOAC reversal is off-label; Adults only; children need paediatric haematology advice; Drug levels (anti-Xa, dabigatran) may not be available quickly; Does not cover antiplatelet reversal or perioperative (non-bleeding) reversal. Individual patient factors may require deviation from these recommendations.
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