Reversal Information
Vitamin K is the antidote to warfarin. It is preferably administered PO or IV; the subcutaneous route may lead to erratic and unpredictable absorption, and the IM route may lead to hematoma development. Vitamin K may be administered alone or in addition to fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC; Kcentra).

• Pharmacokinetics of Vitamin K:
  • Onset: 6-10 hr (PO); 1-2 hr (IV)
  • Peak effect: 24-48 hr (PO); 12-14 hr (IV)
• No bleeding:
  • If rapid reversal not required, hold warfarin for 24 hours and repeat INR.
  • If rapid reversal is required and patient will require warfarin in the near future, give vitamin K 30 mcg/kg/dose PO (max dose: 0.5-2 mg PO) with the expectation that a reduction of INR will occur in 24 hours
  • If rapid reversal is required and no near future warfarin required, give vitamin K 2-5 mg PO with the expectation that a reduction of INR will occur in 24 hours.
  • DO NOT GIVE VITAMIN K TO PATIENTS WITH CARDIAC VALVES, SHUNTS OR CONDUITS; Consult IHTC/cardiac surgeon/cardiologist on call.
• With non-life threatening bleeding:
  • Give vitamin K 0.5-2 mg PO with FFP 20 mL/kg with the expectation that a reduction of INR will occur in 24 hours
  • DO NOT GIVE VITAMIN K TO PATIENTS WITH CARDIAC VALVES, SHUNTS OR CONDUITS; Consult IHTC/cardiac surgeon/cardiologist on call.
    • If necessary to reverse bleeding before contacting IHTC/cardiac surgeon/cardiologist use judicious aliquots of FFP (5-10 ml/kg) to prevent thrombosis.
• With life-threatening bleeding or emergent surgical procedure:
  • Give vitamin K 5-10 mg IV over 10-20 minutes and FFP (20 mL/kg) or KCentra
    • Kcentra may be used in adolescents instead of FFP with standard dose of 25-50 FIX units/kg depending on INR.
      • Dosing:
        • INR 2 to < 4 = 25 FIX units/kg (max dose 2500 IU)
        • INR 4 to 6 = 35 FIX units/kg (max dose 3500 IU)
        • INR > 6 = 50 FIX units/kg (max dose 5000 IU)
      • Don’t exceed stated maximum dose for patient’s weighing > 100 kg.
      • Kcentra is contraindicated in DIC and known HIT.
      • Repeat dosing isn’t recommended and not supported by clinical trials.
      • Vitamin K should be administered following KCentra administration.
      • KCentra should be infused at room temperature at a rate of 0.12 ml/kg/min, up to the maximum rate of 8.4 ml/min. Blood should not enter the syringe being used for administration, as fibrin clots may form. Do not mix with other medications. Administer through a separate infusion line.
      • Time to clinical effect is 30 minutes, with a duration of > 12 hours
    • Vitamin K (1 to 2 mg slow IV) can be repeated every 12 hours depending on the INR. Consider higher vitamin K doses if INR not appropriately decreasing.
  • DO NOT GIVE VITAMIN K TO PATIENTS WITH CARDIAC VALVES, SHUNTS OR CONDUITS; Consult IHTC/cardiac surgeon/cardiologist on call.
    • If necessary to reverse bleeding before contacting IHTC/cardiac surgeon/cardiologist use judicious aliquots of FFP (5-10 ml/kg) to prevent thrombosis.
  • Recombinant factor VIIa (Novoseven) can be considered if patient not responding to vitamin K and KCentra administration (i.e., severe bleeding continues).
• For non-cardiac cases, consult hematology to help guide decision making on reversal agent of choice.

Critical site bleeds: Intracranial hemorrhage, including intraparenchymal, subdural, epidural, and subarachnoid hemorrhages; Other CNS hemorrhage, including intraocular, intra- or extra-axial spinal hemorrhages; Pericardial tamponade; Airway, including posterior epistaxis; Hemothorax, intraabdominal bleeding, and retroperitoneal hemorrhage; Extremity bleeds, including intramuscular and intraarticular bleeding concerning for compartment syndrome, bleeding associated with hemodynamic instability, bleeding in a noncompressible vessel (e.g., subclavian)