Agent-specific reversal for warfarin, dabigatran, factor Xa inhibitors, heparin/LMWH and antiplatelets in major bleeding.
At the bedside
- 1
Assess
Site and severity, last dose time, renal function, INR/aPTT/anti-Xa/TT. General measures: compression, source control, transfusion, stop antithrombotics.
- 2
Warfarin
Vitamin K 5-10 mg IV + 4F-PCC (INR-based 25-50 units/kg, or fixed 1,000-1,500 units); recheck INR 30 min after. FFP 15-20 mL/kg only if PCC unavailable.
- 3
Dabigatran
Idarucizumab 5 g IV; if unavailable, PCC 50 units/kg; haemodialysis removes dabigatran.
- 4
Rivaroxaban/apixaban
Andexanet alfa where available; otherwise 4F-PCC 50 units/kg (or 2,000 units). Activated charcoal if ingested within 2-4 h.
- 5
Heparin/LMWH
Protamine 1 mg per 100 units UFH given in last 2-3 h (max 50 mg); enoxaparin 1 mg per mg (≤ 8 h) or 0.5 mg per mg (8-12 h).
- 6
Antiplatelets
Platelet transfusion not recommended for antiplatelet-associated ICH (PATCH: worse outcome) unless emergency neurosurgery; consider desmopressin 0.3 mcg/kg.
- 7
Thrombolytic-associated bleeding
Cryoprecipitate to fibrinogen > 150 mg/dL and tranexamic acid.
- 8
Restart plan
Decide when to restart anticoagulation (often 7-14 days after ICH, 1-3 days after GI bleed control) with the specialist team.
Warfarin reversal
Four-factor prothrombin complex concentrate
- Dose
- INR 2-4: 25 units/kg; 4-6: 35 units/kg; > 6: 50 units/kg
- Worked example
- 70 kg, INR 5: 35 × 70 = 2,450 units (≈ 5 × 500-unit vials)
Warfarin reversal
Vitamin K1 (phytomenadione)
- Dose
- 5-10 mg slowly
Dabigatran reversal
Idarucizumab
- Dose
- 5 g
Factor Xa inhibitor bleeding (no andexanet)
Four-factor prothrombin complex concentrate
- Dose
- 50 units/kg (or 2,000 units fixed)
- Worked example
- 70 kg: 3,500 units (fixed alternative 2,000 units)
Heparin reversal
Protamine sulfate
- Dose
- 1 mg per 100 units UFH in last 2-3 h (max 50 mg)
- Worked example
- Infusion 1,000 units/h: about 2,500 units in last 2.5 h → 25 mg protamine over 10 min
Antiplatelet/uraemic bleeding
Desmopressin (DDAVP)
- Dose
- 0.3 mcg/kg over 30 min
- Worked example
- 70 kg: 21 mcg in 50 mL NS over 30 min
Reversal summary
| Agent | First line | Alternative |
|---|---|---|
| Warfarin | Vitamin K IV + 4F-PCC | FFP 15-20 mL/kg |
| Dabigatran | Idarucizumab 5 g | PCC 50 units/kg; dialysis |
| Apixaban/rivaroxaban | Andexanet alfa | 4F-PCC 50 units/kg |
| UFH | Protamine | - |
| Enoxaparin | Protamine (partial) | - |
| Fondaparinux | No specific antidote | Consider PCC/rFVIIa (limited data) |
| Antiplatelets | Supportive; desmopressin | Platelets only for neurosurgery |
| Thrombolytics | Cryoprecipitate + TXA | - |
References
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- 3
Major bleed on an anticoagulant
Step 1 of ~4
Stop drug, local control, transfuse, labs
Based on Tomaselli GF, Mahaffey KW, Cuker A, et al. Educational use; follow local protocol.
Pathophysiology
Warfarin depletes vitamin K-dependent factors II, VII, IX, X (PCC replaces them immediately; vitamin K restores synthesis over 6-24 h). DOACs directly inhibit thrombin or factor Xa; reversal requires antidotes or overwhelming the inhibition with factor concentrates.
Evidence
- ACC 2020 ECDP on bleeding with oral anticoagulants [Tomaselli 2020].
- PATCH: platelet transfusion increased death or dependence in antiplatelet-associated ICH (OR 2.05) [Baharoglu 2016].
Controversies
- Andexanet thrombosis risk and cost; PCC for DOACs is off-label with limited evidence.
🇮🇳 India notes
- Andexanet is not available in India and idarucizumab is expensive; 4F-PCC (or FFP if unavailable) is the practical option.
- Acenocoumarol (more commonly used than warfarin in India) is reversed the same way.
References
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Educational reference for trained clinicians. Check doses against your hospital protocol and the patient in front of you.