Reversing Warfarin

Risk factors for bleeding

Bleeding while on oral anticoagulants ⇑ significantly with INR > 5.0, particularly in patients with risk factors for bleeding.

The majority of over-anticoagulated patients will return to their target therapeutic range within 3 days of discontinuing warfarin therapy.

Vit. K1 (C₃₁H₄₆O₂) and K2(C₄₁H₅₆O₂)are naturally occurring fat-soluble vitamins
Essential in the production of prothrombin
Vit K is the 1^st drug of choice to be administered for the reversal of excessive anti-coagulation if the patient has evidence of bleeding
Dispensed in ampoules of 1ml/10mgs (Konakion®) or 0.2mls/2mgs (paediatric Konakion®)
Can be administered sub-lingually using a 1ml syringe and a filter needle to draw up and administer the solution. Vitamin K is also available in 10mg tablets for oral administration
When partial correction is required to achieve a target therapeutic INR, the Intravenous preparation of Vitamin K can be administered in low doses of 1-2mgs sub-lingually
5mgs of Vitamin K will completely reverse anticoagulation, which is only indicated if the patient is presenting with bleeding as a result of a high INR
Particular caution is advised for patients with prosthetic heart valves,. If indicated, small doses of vitamin K only (e.g. 1 – 2 mg) are recommended
Prothrombin Complex Concentrate (PCC) is not routinely administered to reverse excessive anticoagulation in the absence of bleeding but should be administered in life threatening major haemorrhage
PCC is more effective than Fresh Frozen Plasma (FFP) for reversal of bleeding associated with excessive anticoagulation; therefore FFP is not indicated or recommended when PCC is available

Drug	Mech. of action	Half-life	Emergency Reversal
Warfarin	Vitamin K antagonist	20-60 hours	Vitamin K 5g IV ± PCC 25-50 U/kg
DOACs	Mech. of action	Half-life	Emergency Reversal
Dabigatran	Thrombin inhibitor	9 hours (renal fxn.)	TXA 1g IV ± Idaruciumab (€) 5g IV
Rivaroxaban	Factor Xa inhibitor	9 hours (renal fxn.)	Andexanet Alfa (€) or PCC 50 U/kg
Apixaban	Factor Xa inhibitor		Andexanet Alfa (€) or PCC 50 U/kg
Edoxaban	Factor Xa inhibitor		Andexanet Alfa (€) or PCC 50 U/kg
Antiplatelets	Mech. of action	Half-life	Emergency Reversal
Aspirin	Irreversibly inhibits COX1	5-7 days	Platelet transfusion (low-level evidence). Desmopressin (caution with contraindications and limited evidence in trauma)
Clopidogrel	Irreversible inhibits P2YI2 receptors	5-7 days	Platelet transfusion (low-level evidence). Desmopressin (caution with contraindications and limited evidence in trauma)
Prasugrel	Irreversible inhibits P2YI2 receptors	5-7 days	Platelet transfusion (low-level evidence). Desmopressin (caution with contraindications and limited evidence in trauma)
Ticagrelor	Irreversible inhibits P2YI2 receptors	5-7 days	Platelet transfusion (low-level evidence). Desmopressin (caution with contraindications and limited evidence in trauma)
Dipyridamole	Phosphodiesterase inhibitor	24 hours	Platelet transfusion (low-level evidence). Desmopressin (caution with contraindications and limited evidence in trauma)

BaglinTP et al, on behalf of BCSH. Guidelines on oral anticoagulation (warfarin): third edition – 2005 update. British Journal of Haematology 2005: 132:277-285
BaglinTP et al, on behalf of BCSH. Guidelines on oral anticoagulation (warfarin): third edition. British Journal of Haematology 1998; 101:374-387
Baker et al. Warfarin Reversal: Consensus guidelines on behalf of the Australasian Society of Thrombosis and Haemostasis. Med J Australia 2004; 181: 492-497
Ansel et al. The pharmacology and management of Vitamin K antagonists. Chest 2004; 126: 204- 233S

Content by Dr Arina Kruis, Dr Íomhar O' Sullivan 22/09/2020. Last review Dr ÍOS 21/10/25.