Genotyping
CYP2C9 and VKORC1 genotype results may provide directional guidance for warfarin dosing in pediatric patients. Clinical genotyping is available through the CMH Laboratory. Approximately 50% of the variability in warfarin dose-response in adults has been associated with the variants in CYP2C9 and VKORC1 detected by this test. The test does not provide quantitative information which links a specific genotype with a precise warfarin dose and large scale studies looking at genotype and effect have not been performed; however, the results may be useful in clinical decision making when interpreted in the context of other "factors" known to influence the dose-response for warfarin (such as drug-drug interactions, patient age, drug-diet interactions, drug-disease interactions). Consultations provided by the Division of Pediatric Clinical Pharmacology and Medical Toxicology can provide such a multifactorial assessment and thus, may be beneficial.
References
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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. 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
These pathways do not establish a standard of care to be followed in every case. It is recognized that each case is different, and those individuals involved in providing health care are expected to use their judgment in determining what is in the best interests of the patient based on the circumstances existing at the time. It is impossible to anticipate all possible situations that may exist and to prepare a pathway for each. Accordingly, these pathways should guide care with the understanding that departures from them may be required at times.