Poster Topical Area: Vitamins and Minerals
Location: Hall D
Poster Board Number: 478
Warfarin (W) is an oral anticoagulant widely prescribed for the prevention of thromboembolic conditions, such as atrial fibrillation and deep vein thrombosis. The safety and efficacy of W therapy are highly dependent on its stability within a narrow therapeutic range. Individuals undergoing W treatment are currently advised to aim for stable daily VK intakes as VK is involved in the bioactivation of factors II (prothrombin), VII, IX and X (all procoagulants), and proteins C, S, and Z (inhibitors of the procoagulant system). Yet reports point to W-treated patients still being instructed to limit or avoid VK rich foods, a recommendation resulting in lower VK intakes. In the present study, we investigated the specific impact of low VK intakes on the coagulation activity of four VK-dependent factors, and clotting times, in W-treated rats. Male Wistar rats were randomly allocated to a AIN-93 based diet containing low (L: 80 mcg/kg/d; n=20) or adequate (A: 750 mcg/kg/d; n=20) phylloquinone (K1) containing diet. After one week, half the animals from each diet group were randomly allocated to receive, by gavage, daily doses of W (W gp; 0.2 mg W/kg/d) in a vehicle, or vehicle only (C gp), for 20 days. Coagulation activity was assessed for factors II, VII, IX and X, and clotting times were based on prothrombin (PT) and activated thromboplastin times (APTT). Measures were obtained at the end of the study and were conducted in the hospital clinical laboratory using standard procedures. For each diet group, factor activity and clotting times are presented as % values of their respective controls. Diet group differences were analyzed using Student’s t-test. Compared to animals from the A gp, rats on the L diet presented significant decreases in relative activities for FVII (39%) and FX (33%) (p<0.05), [FII (44 %) not quite reaching statistical significance (p=0.06)], and a significant increase in relative PT (37 %) (p<0.05). APTT was not significantly affected by diet. Results from this study provides additional evidence for the modulatory role of dietary VK on coagulation factor activities and resulting clotting times, and stress the importance of ensuring adequate VK intake in patients undergoing anticoagulation therapy with W derivatives.
Funding Source: This study was funded by CIHR.
Université de Montréal
Montreal, Quebec, Canada