<strong>Warfarin</strong> <strong>Monitoring</strong> Table I Clinical Management <strong>of</strong> the Supratherapeutic INR* *Data from Ansell, 2004 and other sources. The purpose <strong>of</strong> this table is to convey general guidelines for the treatment <strong>of</strong> a supratherapeutic INR. Clinical judgment is required for the individual patient. <strong>Warfarin</strong> Risks and Side Effects 6
<strong>Warfarin</strong> <strong>Monitoring</strong> tient is actively bleeding and the INR needs to be corrected acutely, fresh frozen plasma can be administered with vitamin K and in extreme 12cases prothrombin complex concentrates can be given. When a patient is found to have a markedly elevated PT without active bleeding, a more conservative approach is warranted such as simply skipping dosages until the INR returns to the appropriate range (Table I). <strong>Warfarin</strong>-induced skin necrosis is a rare but significant side effect. It follows administration by one to ten days, is heralded by parasthesia and an erythematous flush, which is followed by petechiae and hemorrhage which leads to skin necrosis. Skin necrosis is most commonly associated with proctein C deficiency and occasionally protein S deficiency. Protein C has a very short half-life and a rapid decline in activity from over 50% to less than 5% apparently initiates the development <strong>of</strong> skin necrosis in these patients. Therefore, screening for protein C and S deficiencies in patients with deep venous thrombosis may help to identify those with an increased risk <strong>of</strong> skin necrosis. Ansell, J. et al. The Pharmacology and Management <strong>of</strong> the Vitamin K Antagonists: The Seventh ACCP Conference on Antithrombotic and Thrombolytic <strong>Therapy</strong>. Chest 126: 204- 233, 2004. DeLoughery, T.G. “Oral anticoagulants” in Disorders <strong>of</strong> Hemostasis and Thrombosis, a Clinical Guide, Second Edition. Eds Goodnight, S.H. Jr. & Hathaway, W.E.. The McGraw- Hill Companies, New York, pp. 553-566, 2001. Fairweather, R.B., Ansell, J., van den Besselaar, A.M.H.P., Brandt, J.T., Bussey, H.I., Poller, L., Triplett, D.A. & White, R.H. College <strong>of</strong> American Pathologists Conference XXXI on laboratory monitoring <strong>of</strong> anticoagulant therapy. <strong>Laboratory</strong> monitoring <strong>of</strong> oral anticoagulant therapy. Arch. Pathol. Lab. Med. 122:768-781, 1998. Gage, B.F. et al. Management and dosing <strong>of</strong> warfarin therapy. Am. J. Med. 109:481– 488, 2000. Hirsh, J. Oral anticoagulants: Mechanism <strong>of</strong> action, clinical effectiveness, and optimal therapeutic range. Chest 119: 8S-21S, 2001. Jaffer, A.K. et al. Low–Molecular-Weight- Heparins as Periprocedural Anticoagulation for Patients on Long-Term <strong>Warfarin</strong> <strong>Therapy</strong>: A Standardized Bridging <strong>Therapy</strong> Protocol. J. Thromb. Thrombolysis. 20:11-16, 2005. Mueller, R.L. First-generation agents: aspirin, heparin and coumarins. Best Pract. Res. Clin. Haematol. 17:23-53, 2004. Riley, R.S., Fisher, L.M., and Rowe, D. Clinical utilization <strong>of</strong> the International Normalized Ratio (INR). J. Clin. Lab. Anal. 14:101-114, 2000. Sconce, E.A. The impact <strong>of</strong> CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood. 106:2329-2333, 2005. Tie, J.K., Nicchitta, C., von Heijne, G. & Stafford, D.W. Membrane topology mapping <strong>of</strong> vitamin K epoxide reductase by in vitro translation/cotranslocation. J. Biol. Chem. 280: 16410-16416, 2005. Wallin, R. and Hutson, S.M. <strong>Warfarin</strong> and the Vitamin K-Dependent !-Carboxylation System. Trends Mol. Med. 10: 299-302, 2004. References 7