The association of vitamin K status with warfarin sensitivity at the onset of treatment

• Published in: British journal of haematology 2001-03, Vol.112 (3), p.572-577
• Main Authors: Cushman, Mary, Booth, Sarah L., Possidente, Carl J., Davidson, Kenneth W., Sadowski, James A., Bovill, Edwin G.
• Format: Article
• Language: English
• Subjects: Aged; Anticoagulants - therapeutic use; anticoagulation; Biological and medical sciences; Biomarkers; Blood. Blood coagulation. Reticuloendothelial system; drug monitoring; Female; Hematology; Humans; International Normalized Ratio; Linear Models; Male; Medical sciences; Middle Aged; Nutritional Status; Pharmacology. Drug treatments; Preoperative Care - methods; Protein Precursors - analysis; Prothrombin - analysis; Treatment Outcome; Triglycerides - analysis; vitamin K; Vitamin K - metabolism; Vitamin K 1 - analogs & derivatives; Vitamin K 1 - analysis; warfarin; Warfarin - therapeutic use
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2001.02635.x

We investigated the association of vitamin K status with warfarin sensitivity among 40 orthopaedic patients beginning perioperative algorithm‐dosed warfarin. Baseline vitamin K status was assessed using plasma vitamin K‐1 and vitamin K‐1 2,3 epoxide concentrations, and a questionnaire‐based estimation of usual vitamin K intake. Warfarin sensitivity was assessed as the increase in the International Normalized Ratio (INR) after two doses of 5 mg of warfarin and as the 4‐d accumulation of under‐γ‐carboxylated prothrombin (PIVKA‐II), adjusted for warfarin dose requirement. Multivariate models were used to assess vitamin K variables as predictors of warfarin sensitivity. The mean INR increase was 0·53 U and the mean PIVKA‐II increase was 771 ng/ml/mg warfarin. Demographic factors were not associated with warfarin response. For each 1 standard deviation (SD) lower value of plasma vitamin K‐1, but not the other vitamin K variables, the INR rose 0·24 U (P ≤ 0·01). A higher usual vitamin K intake and plasma vitamin K‐1, and lower plasma vitamin K‐1 2,3 epoxide, were all associated with a lower PIVKA‐II increase over 4 d. Respective differences in PIVKA‐II accumulation per SD increase of each variable were −165, −218 and 236 ng/ml/mg warfarin (all P ≤ 0·05). We concluded that dietary and biochemical measures of vitamin K status were associated with early warfarin sensitivity.