Warfarin Antidotes

• Antidotes:

  • Vitamin K (phytonadione)

  • Kcentra

  • FFP (fresh frozen plasma)

• Choice and dose is dependent on the clinical problem, no bleeding vs. significant bleeding, and need for future warfarin therapy.

• If patient requires rapid warfarin reversal but has no bleeding, insignificant bleeding or bruising:

  • Vitamin K 30 mcg/kg by slow IV infusion over 10-20 minutes (to avoid anaphylaxis). Max dose 2 mg.

    • This weight adjusted regimen is safer for pediatric patients than a universal dosage (i.e. 0.5 - 2mg) as recommended for adults. Even 0.5 mg (sufficient for many adults) is likely to be too high for most young children. Seriously ill children with liver dysfunction may require more than a single dose. Oral vitamin K is effective in adults but the INR fall is slower than IV injection.

  • The preferred route is IV, but in a child with poor or no venous access, the PO or SQ route may be used, particularly if the INR is 6-10. The PO route is preferred.

  • The IM route is NOT recommended.

• If patient has significant bleeding:

  • Not life threatening and will not cause morbidity:

    • Vitamin K 30 mcg/kg by slow IV infusion over 10-20 minutes (to avoid anaphylaxis). Max dose 2 mg.

    • Kcentra:

      • Administer with vitamin K concurrently.
      • Dosing based on pretreatment INR:
        
        

      Pretreatment INR	Dose (in units of factor IX activity)	Maximum Dose
      2 to <4	25 units/kg	2500 units
      4 to 6	35 units/kg	3500 units
      >6	50 units/kg	5000 units

• • • • Check INR stat 30 minutes after end of Kcentra infusion:
        • If INR < 1.5, proceed with procedure.
        • If INR > 1.5 or bleeding not controlled, contact the Coagulation Consult Service immediately.

    • Consider FFP 20 mL/kg IV.

  • Life threatening and will cause morbidity:

    • Vitamin K 30 mcg/kg IV by slow IV infusion over 10-20 minutes (to avoid anaphylaxis). Max dose 5 mg.

    • And FFP 20 mL/kg IV.

    • Kcentra:

      • Administer with vitamin K concurrently.
      • Dosing based on pretreatment INR:
        
        

      Pretreatment INR	Dose (in units of factor IX activity)	Maximum Dose
      2 to <4	25 units/kg	2500 units
      4 to 6	35 units/kg	3500 units
      >6	50 units/kg	5000 units

      • Check INR stat 30 minutes after end of Kcentra infusion:
        • If INR<1.5, proceed with procedure.
        • If INR>1.5 or bleeding not controlled, contact the Coagulation Consult Service immediately.

    • Consider giving NovoSeven RT 90 micrograms/kg IV (alternate choice).

• Safety of IV administration:

  • The standard product for IV administration of Vitamin K at CMH is the 2 mg/mL concentration, which is readily available in medication stations on every inpatient unit.

  • This dilute form (2 mg/mL) along with slow IV infusion over 10 to 20 minutes may avoid anaphylaxis that has been associated with IV administration of vitamin K.

  • Where the concentrated 10 mg/mL product is available, it must be diluted to 2 mg/mL with D5W or NS prior to administration.
    
    

References

Ansell, J., Hirsh, J., Hylek, E., Jacobson, A., Crowther, M., & Palareti, G. (2008). Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest, 133(6 Suppl), 160s-198s. https://doi.org/10.1378/chest.08-0670


Bolton-Maggs, P., & Brook, L. (2002). The use of vitamin K for reversal of over-warfarinization in children. Br J Haematol, 118(3), 924. https://doi.org/10.1046/j.1365-2141.2002.03631_5.x



David, M., et al. (2004, May). Warfarin Therapy in Children. Thrombosis Interest Group of Canada. Retrieved Oct 21, 2008 from http://www.tigc.org/eguidelines/warfarinchildren04.htm.



Horton, J. D., & Bushwick, B. M. (1999). Warfarin therapy: evolving strategies in anticoagulation. Am Fam Physician, 59(3), 635-646.



Lexicomp Online, Pediatric and Neonatal Lexi-Drugs. Kcentra. Retrieved Oct 2008, from https:online.lexi.com. 

Lexicomp Online, Pediatric and Neonatal Lexi-Drugs. Warfarin. Retrieved Oct 2008, from https:online.lexi.com.



Monagle, P., Chan, A. K. C., Goldenberg, N. A., Ichord, R. N., Journeycake, J. M., Nowak-Göttl, U., & Vesely, S. K. (2012). Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest, 141(2 Suppl), e737S-e801S. https://doi.org/10.1378/chest.11-2308



Monagle, P., Cuello, C. A., Augustine, C., Bonduel, M., Brandão, L. R., Capman, T., Chan, A. K. C., Hanson, S., Male, C., Meerpohl, J., Newall, F., O'Brien, S. H., Raffini, L., van Ommen, H., Wiernikowski, J., Williams, S., Bhatt, M., Riva, J. J., Roldan, Y., . . . Vesely, S. K. (2018). American Society of Hematology 2018 Guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism. Blood Adv, 2(22), 3292-3316. https://doi.org/10.1182/bloodadvances.2018024786



Roach, E. S., Golomb, M. R., Adams, R., Biller, J., Daniels, S., Deveber, G., Ferriero, D., Jones, B. V., Kirkham, F. J., Scott, R. M., & Smith, E. R. (2008). Management of stroke in infants and children: a scientific statement from a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young. Stroke, 39(9), 2644-2691. https://doi.org/10.1161/strokeaha.108.189696