Investigation of patients with abnormal response to warfarin.

Abstract

1 In 55 patients in whom warfarin control had been satisfactory for at least 4 months, warfarin dose, plasma warfarin concentration and plasma clearance were measured. 2 The mean dose to maintain the BCR (INR) between 2.3 and 3.3 was 5.1 + 2 mg dayt1 (range 1.5-10 mg). Plasma warfarin concentrations and warfarin clearance were lognormally distributed with 95% confidence limits between 0.8 and 2.4 mg 17' and 2.5 and 8.71 day-1 respectively. These confidence limits were used to construct algorithms which correctly predicted the cause of abnormal warfarin sensitivity in two patients and resistance in two further patients. 3 These algorithms should help to identify the cause of abnormal warfarin responsiveness in the clinical setting.

Clinical utilization of the international normalized ratio (INR)

“…In a recent study of 50 outpatients receiving warfarin and followed for at least 8 weeks, Lubetsky and collaborators found that 16 (32%) had a daily vitamin-K intake of >250 mg/day and required a higher maintenance dosage of warfarin than did other patients to maintain an INR >2.0 (142). Algorithms based on measurements of plasma warfarin concentration and plasma clearance in stable patients were published by Bentley et al for use in predicting the cause of abnormal warfarin responsiveness (143).…”

Anticoagulant therapy in special circumstances

“…These patients initially require the usual doses of warfarin therapy but then present with normal INRs despite massive warfarin doses. Measuring serum warfarin levels are usefully in patients suspected noncompliance [46]. Patients with undetectable warfarin levels despite allegedly being on large doses of warfarin are most likely not takin the drug.…”

Vitamin K Metabolism in a Patient Resistant to Vitamin K Antagonists

“…Therefore the upper limit of mean + 5 SD is situated at approximately 50 mg/day. An abnormal response to warfarin and other vitamin K antagonists may be due to: (1) a shortened half-life of the drug, as occurs with enzyme-inducing agents such as barbiturates [13]; (2) an unusually high dietary vitamin K, intake [14] (some vegetables such as spinach, Vitamin K. Metabolism in a Patient Resistant to Vitamin K Antagonists broccoli and cauliflower contain up to 0.7 mg of vitamin Ki/100g); (3) impaired intestinal absorption of the drug due to a state of malab sorption [12] or the administration of choles tyramine; (4) poor compliance of the patient [15], and (5) hereditary warfarin resistance [16,17], These 5 possible etiologies were sys tematically investigated.…”