Major Haemorrhage on Anticoagulation

Life-threatening bleeding on anticoagulation requires immediate reversal using agent-specific antidotes. The major haemorrhage protocol (MHP) should be activated for haemodynamically significant bleeding. Anticoagulation restart decisions are made…

BSH/NICE Anticoagulant Reversal Protocol

The pathway

1 · Activate major haemorrhage protocol

Criteria: SBP <90, blood loss >2L, haemorrhage requiring ≥4 units pRBC, or critical site (intracranial, spinal, pericardial)
Notify haematology, blood bank, and senior clinical team
Send: FBC, PT/INR, APTT, fibrinogen, group & save/crossmatch, anti-Xa level (for LMWH/DOAC)

2 · Warfarin reversal

INR >8 without bleeding: Vitamin K 1–2mg PO or 0.5–1mg IV
INR >8 with minor bleeding: Vitamin K 3mg IV + consider PCC
Any bleeding with haemodynamic instability: Vitamin K 5–10mg IV + 4-factor PCC (Beriplex/Octaplex) 25–50 IU/kg
PCC works within minutes; Vitamin K takes 6–12 hours

3 · Dabigatran reversal

Idarucizumab (Praxbind) 5g IV as two sequential 2.5g doses over 5–10 minutes each
Specific antidote to dabigatran — reverses within minutes
Use for life-threatening or uncontrolled bleeding, or emergency surgery within 8h
Check thrombin time (TT) or dilute TT to guide; APTT less reliable

4 · Rivaroxaban / Apixaban / Edoxaban reversal

Andexanet alfa (Ondexxya): specific antidote for factor Xa inhibitors
High-dose: 800mg IV bolus then 8mg/min for 120 minutes (rivaroxaban ≥10mg or apixaban ≥5mg within 8h)
Low-dose: 400mg IV bolus then 4mg/min for 120 minutes
If andexanet alfa unavailable: 4-factor PCC 50 IU/kg as alternative
Check anti-Xa level (drug-specific assay)

5 · LMWH reversal

Protamine sulphate: neutralises unfractionated heparin completely, LMWH partially
1mg protamine per 100 units UFH (max 50mg IV over 10 minutes)
For LMWH: if within 8 hours: 1mg protamine per 1mg enoxaparin; partial reversal only (~60–70%)
Warn of risk of anaphylaxis (fish allergy, previous protamine exposure)

6 · Supportive haemostatic measures

Tranexamic acid 1g IV over 10 minutes for traumatic or surgical haemorrhage (not intracranial)
FFP 15ml/kg if coagulopathy without specific agent available
Cryoprecipitate if fibrinogen <1.5g/L
Packed RBCs to Hb >80g/L (>100 in ACS)
Platelet transfusion if <50 × 10⁹/L with bleeding

7 · Anticoagulation restart decision

Do not restart within 24–48 hours in most cases
AF (CHA₂DS₂-VASc ≥2): restart at 4–8 weeks — balance stroke vs bleed risk
Mechanical heart valves: discuss urgently with cardiothoracic team — early bridging may be needed
VTE within 3 months: high thrombotic risk — consider IVC filter as bridge
Decision documented with patient + multidisciplinary team

Drugs

Drug	Dose	Route	Notes
4-factor PCC (Beriplex / Octaplex)	25–50 IU/kg	IV	Warfarin/VKA reversal, or when a specific DOAC antidote is unavailable. Works within minutes. Give vitamin K alongside it for VKA reversal only — vitamin K does nothing for a DOAC. Repeat dosing is not recommended (Beriplex SmPC: not supported by clinical data).
Vitamin K (phytomenadione)	5–10mg	IV	For warfarin/VKA reversal only — not for DOAC bleeding. Co-administer with PCC; takes 6–12h to work, so PCC provides the immediate cover. IV preferred over oral in major bleeding.
Idarucizumab (Praxbind)	5g (as 2 × 2.5g doses)	IV	Specific dabigatran antidote. Give both doses within 15 minutes. Reversal within 5 minutes.
Andexanet alfa (Ondexxya)	400–800mg bolus then 4–8mg/min for 120 min	IV	Factor Xa inhibitor antidote (rivaroxaban, apixaban). Dose depends on DOAC dose and timing. Specialist pharmacy involvement required.
Protamine sulphate	1mg per 100 units UFH (max 50mg)	IV slow	Heparin/LMWH reversal. Give over 10 minutes. Risk of anaphylaxis — resuscitation equipment at bedside.
Tranexamic acid	1g over 10 minutes	IV	Adjunct for traumatic or surgical haemorrhage. AVOID in haematuria (risk of clot retention) and subarachnoid haemorrhage without trauma.

When to escalate

Intracranial haemorrhage — immediate neurosurgical and haematology review, reverse within 30 minutes,SBP <90 despite initial resuscitation — activate MHP, ITU referral,Ongoing haemorrhage despite reversal agent — surgical/interventional radiology,Dabigatran toxicity with renal failure — consider haemodialysis (dabigatran is dialysable),Mechanical heart valve patient with major bleed — urgent cardiothoracic input for bridging strategy,INR not correcting after PCC — haematology now. Check fibrinogen and for DIC; repeat PCC dosing is NOT routinely recommended

Reference: BSH Guideline on the Use of Anticoagulant Reversal Agents 2022 / NICE NG196

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