Anticoagulation with Warfarin
Warfarin is a widely used oral anticoagulant for the prevention and management of thromboembolism.
Warfarin works by blocking the gamma-carboxylation of glutamic acid residues of the Vitamin K−dependent coagulation factors II, VII, IX and X.
This inhibition results in the decreased biological activity of factors II, VII, IX, X, and protein C and protein S, causing the prolongation of the international normalised ratio (INR).
Bleeding is the most common complication of Warfarin use, with an annual incidence of warfarin-associated major bleeding of 1%-3%.
The direct oral anticoagulants (DOAC) provide alternatives to warfarin for managing thromboembolic disease in certain patient populations.
Management of an elevated INR caused by warfarin therapy
When considering how to manage patients receiving warfarin who require surgery, the risk of thrombosis if warfarin is withheld needs to be balanced with the risk of bleeding if continued.
Major bleeding or urgent surgery are commonly encountered and require prompt reversal of warfarin anticoagulation to counteract the prolonged inhibition of vitamin K-dependent factors.
Vitamin K alone has been shown to be effective in warfarin reversal, but its full effect typically takes 12–24 hours. Where rapid reversal of INR is required (ie, emergency surgery, major bleeding), the use of 4-factor PCC (Beriplex®) is recommended.
When Beriplex® is used in life-threatening warfarin-related bleeding (in conjunction with IV Vitamin K), FFP is not required for reversal of the warfarin effect as Beriplex® contains sufficient amounts of all 4 of the vitamin K-dependent coagulation factors. FFP may however, be required for associated major haemorrhage as directed by the local Major Haemorrhage Protocols.
THANZ has produced updated recommendations for warfarin reversal in the setting of four-factor prothrombin complex concentrate. All dosing decisions should consider the individual patient, including:
• their degree of bleeding
• the ability to perform timely and adequate haemostatic interventions and
• their underlying thrombotic risk that warranted anticoagulation with warfarin in the first place
In patients > 100 kg, the dose of 4-factor PCC should be calculated based on a capped 100 kg body weight and maximum dose of 50 IU/kg (i.e. maximum dose of 5000 IU).
Management of patients on warfarin therapy WITH bleeding
- Table 1: Management of patients on warfarin therapy with bleeding
INR and bleeding risk Warfarin Vitamin K Beriplex®3,4 Check INR Comments INR ≥ 1.5 with life-threatening or critical organ bleeding Omit
5–10 mg IV1
50 IU/kg
Cap weight at 100 kg. If INR 1.5–1.9 consider dose < 50 IU/kg.
In 20–30 mins
Ongoing use of warfarin should be reviewed. If warfarin must continue, resume after bleeding ceases and adjust dose to maintain INR within therapeutic range. INR ≥ 2.0 with clinically significant bleeding (not life-threatening) Omit
5–10 mg IV1
25–50 IU/kg
Cap weight at 100 kg. Dose based on patient factors and INR (see PI).
In 20–30 mins Any INR with minor bleeding INR > 4.5 or major bleeding risk is high Omit
Consider 1–2 mg PO
or 0.5–1 mg IV2
If INR > 10 consider a higher dose (see table 2)
If INR > 10 and major bleeding risk is high, consider Beriplex® (see table 2 and seek expert advice) In 24 hours Adjust warfarin dose to maintain INR in target range. Major bleeding risk is low and INR ≤ 4.5 Omit
In 24 hours
1 Child: 0.3 mg/kg IV (max 10 mg), 2 Child: 0.03 mg/kg IV (max 1 mg), 3 All dosing decisions should be based on individual patient factors and local protocols, 4 Co-administration of FFP not required for reversal of warfarin effect with Beriplex®
Warfarin reversal in patients WITHOUT bleeding
Warfarin cessation before surgery needs to balance the thrombotic risk if warfarin is temporarily stopped against the risk of bleeding related to the ongoing anticoagulation. For patients on warfarin, the periprocedural bleeding risk can be significant, occurring in up to nearly 25% of cases.
The updated 2024 THANZ recommendations for warfarin reversal in the setting of four-factor prothrombin complex concentrate advise that the management of non-bleeding patients on warfarin remain unchanged (from the 2013 update of consensus guidelines for warfarin reversal).
In elective surgery, either omission of warfarin alone or with co-administration of vitamin K is the recommended pathway for warfarin reversal.
Outside of the peri-operative setting, Beriplex® should only be considered if INR > 10, and there is a high risk of bleeding.
WYSIWYG Accordion
- Table 2: Management of patients on warfarin therapy without bleeding
INR Major bleeding risk Warfarin Vitamin K Beriplex® Check INR Comments INR higher than therapeutic range but < 4.5 Reduce or
omit next doseResume warfarin at reduced dose when INR approaches target range.
Consider reasons for elevated INR and closely monitor over the following week.
INR 4.5–10.0 Low Omit In 24 hours High Omit Consider 1–2 mg PO or 0.5–1 mg IV1 INR > 10.0 Low Omit 3–5 mg PO or IV2 In 12–24 hours High Omit 3–5 mg PO or IV2 Consider 15–30 IU/kg Cap weight at 100 kg In 12–24 hours 1 Child: 0.03 mg/kg IV (max 1 mg), 2 Child: 0.1 mg/kg IV (max 5 mg)
Suggested Beriplex® dose3, 4 for urgent warfarin reversal in a non-bleeding patient (e.g. before surgery)
WYSIWYG Accordion
- Initial international normalised ratio (INR)
Target INR 1.5 - 2.5
2.6 - 3.5
3.6 - 10.0
> 10.0
0.9 - 1.3 30 IU/kg
35 IU/kg
50 IU/kg
50 IU/kg
1.4 - 2.0 15 IU/kg
25 IU/kg
30 IU/kg
40 IU/kg
3 Cap weight at 100 kg, 4 Vitamin K: recommended for more sustained reversal
Dosing needs to be individualised, considering the patient’s underlying thrombotic risks as well as the indication for warfarin reversal and potential for high-risk bleeding associated with invasive procedures.
Related resources
Further information
Related topics
External resources
Robinson D, McFadyen J, Merriman E, Wee TC, Baker R, Tran H. Updated recommendations for warfarin reversal in the setting of four-factor prothrombin complex concentrate. Medical Journal of Australia. https://doi.org/10.5694/mja2.52538