Use of warfarin has appropriately been increasing with the age of the population and the indications for which there is evidence supporting its use.

Patients undergoing warfarin therapy may have supratherapeutic INRs due to a number of factors, such as lack of monitoring, dietary changes, warfarin absorption changes, drug interactions, medication dosing errors or hepatic disease.

When patients present with elevated INR, the 1998 ACCP recommendations are often used to determine appropriate actions to be taken.

• INR <5 (no significant bleeding)
• Lower or omit a dose
• Closely monitor
• When warfarin is resumed, do so at a lower dose
• If the INR is only minimally above the therapeutic range; no intervention may be necessary (monitor)
• INR >5 and <9 (no significant bleeding)
• Omit next few doses
• Closely monitor
• When warfarin is resumed, do so at a lower dose
• High risk for bleeding
• Administer 1-2.5 mg of oral Vitamin K ₁
• May repeat this dose if adequate reversal has not occurred in 24 hours
• INR >9 (no significant bleeding)
• Omit doses until patient is therapeutic
• Closely monitor
• When warfarin is resumed, do so at a lower dose
• Administer 3-5 mg of oral Vitamin K ₁ (expect the INR to substantially reduce within 24-48 hours)
• May repeat the dose of vitamin K1 in 24-48 hours if adequate reversal has not occurred
• INR >20 (bleeding present, serious but not life threatening)
• Omit doses until patient is therapeutic
• Closely monitor
• When warfarin is resumed, do so at a lower dose
• Administer 10 mg of Vitamin K ₁ by slow IV infusion (may be repeated every 12 hours if needed)
• Administer Fresh Frozen Plasma (FFP) or Prothrombin Complex Concentrate (PCC)
• If there is life threatening bleeding
• Hold warfarin therapy
• Administer Prothrombin Complex Concentrate
• Administer vitamin K ₁ , 10 mg by slow IV
• Repeat this treatment as necessary depending upon the INR

INR >20 with serious bleeding

Hold further warfarin therapy and administer vitamin K, 10 mg by slow IV infusion. Administer fresh frozen plasma (FFP) or prothrombin complex concentrate, depending on the urgency of the situation. Administration of vitamin K can be repeated every 12 hours (grade 2C).

Notes:

1. After initiation of warfarin, effects of prolonged INR become evident within 2-7 days
2. When Vitamin K ₁ is administered, especially repetitively or at high doses; the patient will often be resistant to the effects of warfarin for up a 5-7 days (some may require heparin therapy if anticoagulation is required)
3. Prothrombin complex concentrate (PCC) facts:
• Is available in several forms
• Is a highly concentrated product with factors II, VII, IX, and X (Vitamin K dependent coagulation factors)
• It appears to more rapidly, fully and safely reverse the affects of warfarin therapy as compared the administration of fresh frozen plasma (FFP)
• Vitamin K1 should be administered simultaneously to maintain improvements in the INR
• PCC requires markedly less volume to be infused and thus does not result in issues with fluid overload which are seen with use of FFP
4. Dosing for FFP is usually 10-20 mL/kg for clotting factor deficiencies; however, in more serious hemorrhage, doses of 15-30 mL/kg are usually indicated
5. Dosing for PCC is usually 25-50 U/kg (50 U/kg favored for life threatening bleeding)

Reference:

1. Ansell J, Hirsh J, Dalen J, et al. Managing Oral Anticoagulant Therapy. Chest . 2001;119:22S-38S.
2. Demeyere R, Arnout J, Strengers P. Prothrombin complex concentrate versus fresh frozen plasma in patients on oral anticoagulant therapy undergoing cardiac surgery: a randomized study. Critical Care . 2006;10 (Suppl 1):233.
3. Hirsh J, Dalen JE, Anderson DR, et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest . 1998;114(5_Suppl);445S-469S.
4. Lankiewicz MW, Hays J, Friedman KD, et al. Urgent reversal of warfarin with prothrombin complex concentrate. J Thromb Haemost . 2006;4:967-70.