The association of vitamin K status with warfarin sensitivity at the onset of treatment.
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-gamma-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 < or = 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 < or = 0.05). We concluded that dietary and biochemical measures of vitamin K status were associated with early warfarin sensitivity.
Department of Medicine, University of Vermont, 208 South Park Drive, Suite 2, Colchester, VT 05446, USA. mcushman@salus.uvm.edu
M
M
Cushman
S L
SL
Booth
C J
CJ
Possidente
K W
KW
Davidson
J A
JA
Sadowski
E G
EG
Bovill
D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D015415:Biomarkers; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D011300:Preoperative Care / Q000379:methods*; D011498:Protein Precursors / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D016896:Treatment Outcome; D014280:Triglycerides / Q000032:analysis; D014812:Vitamin K / Q000378:metabolism*; D010837:Vitamin K 1 / Q000031:analogs & derivatives* / Q000032:analysis; D014859:Warfarin / Q000627:therapeutic use*
D000925:Anticoagulants; D015415:Biomarkers; D011498:Protein Precursors; D014280:Triglycerides; D014812:Vitamin K; C016186:vitamin K1 oxide; C008208:acarboxyprothrombin; D014859:Warfarin; D010837:Vitamin K 1; D011516:Prothrombin