title: Appraisal of current vitamin K dosing algorithms for the reversal of over-anticoagulation with warfarin: the need for a more tailored dosing regimen.
abstract: Warfarin is the most commonly prescribed oral anticoagulant in the UK for the treatment and prevention of thromboembolic disorders. Vitamin K administration is an effective way of reversing excessive anticoagulation. Over-anticoagulated patients present with a wide range of international normalized ratio (INR) values and may respond differently to a fixed dose of vitamin K. Current dosing algorithms for vitamin K administration in the non-urgent treatment of over-anticoagulation do not take this variability in response into account. Consequently, over a third of over-anticoagulated patients still remain outside their target INR 24 h after treatment. Such patients are therefore prone to either haemorrhage (if the patient is still over-anticoagulated) or thromboembolism (if the INR reversal is over-corrected). A number of factors such as patient age, body weight, co-morbidity, frailty, warfarin daily dose and CYP2C9 and VKORC1 polymorphism could affect response to vitamin K and thus the rate and extent of INR reversal. There is a need for a more individualized approach to the reversal of over-anticoagulation in asymptomatic or mildly haemorrhagic patients in order to improve the safety of warfarin therapy.
authors.affiliation: Wolfson Unit of Clinical Pharmacology, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Sconce
authors.forename: Farhad
authors.initials: F
authors.lastname: Kamali
mesh_terms: D000368:Aged; D000465:Algorithms; D000925:Anticoagulants / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001777:Blood Coagulation / Q000187:drug effects*; D065729:Cytochrome P-450 CYP2C9; D005838:Genotype; D006470:Hemorrhage / Q000188:drug therapy; D006801:Humans; D019934:International Normalized Ratio; D006899:Mixed Function Oxygenases / Q000235:genetics; D011110:Polymorphism, Genetic; D013923:Thromboembolism / Q000188:drug therapy* / Q000517:prevention & control; D014812:Vitamin K / Q000008:administration & dosage*; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases