Anticoagulant therapy, vitamin

Due to bleeding risk, individuals on anticoagulant therapy or individuals who are vitamin K-deficient should not take vitamin E supplementation without close medical supervision. Absent of that, vitamin E is a well-tolerated relatively non-toxic nutrient. A tolerable upper intake level of 1,000 mg daily of a-tocopherol of any form (equivalent to 1,500 IU of RRR a-tocopherol or 1,100 IU of all-rac-a-tocopherol) would be, according to the Food and Nutrition Board of the Institute of Medicine, the highest dose unlikely to result in haemorrhage in almost all adults. 

Excessive vitamin C doses Diabetics, patients prone to recurrent renal calculi, those undergoing stool occult blood tests and those on sodium restricted diets or anticoagulant therapy should not take excessive doses of vitamin C over an extended time period. 

Warfarin antagonists include vitamin K, barbiturates, glutethimide. rifampin, and cholestyramine. Warfarin potentiators include phenylbutazone. oxyphenbutazone, anabolic steroids, clofibrate, aspirin, hepatotoxins, disnlfirain, and metronidazole. In patients undergoing anticoagulation therapy with warfann, it has been found that cimetidine (used in therapy of duodenal ulcer) may increase anticoagulant blood levels and consequently prolong the prothrombin time. 

Very high intakes may antagonize vitamin K and hence potentiate anticoagulant therapy. This is probably the result of inhibition of the vitamin K quinone reductase, but a-tocopheryl quinone may compete with vitamin K hydroquinone and hence inhibit carboxylation of glutamate in target proteins (Section 5.3.1). 

The usual method of assessing vitamin K nutritional status, or monitoring the efficacy of anticoagulant therapy, is a functional test of blood clotting, and hence the ability to synthesize the vitamin K-dependent clotting factors. 

Bleeding disorders, anticoagulant therapy, or vitamin K deficiency... 

Vitamin E is considered nontoxic at levels up to 3200 mg/day. It has not been found to be teratogenic, mutagenic, or carcinogenic at doses below 1 g/kg of body weight. Vitamin E can heighten the effect of vitamin K deficiency (coagulation defect) or anticoagulation therapy. A recent study, however, indicates that it may be the oxidation product a-tocoquinone that causes the effect (46). 

Shields RC, McBane RD, Kuiper JD, Li H, Heit JA. Efficacy and safety of intravenous phytonadione (vitamin Kl) in patients on long-term oral anticoagulant therapy. Mayo Clin Proc 2001 76(3) 260-6. 

Aspirin potentiates the anticoagulant effect of warfarin and other coumarins because of its inhibitory effect on platelet aggregation and inhibition of vitamin K synthesis. Ibuprofen may also enhance the effect of anticoagulants. Patients on anticoagulant therapy should avoid over-the-counter (OTC) aspirin and ibuprofen. 

It is used to assess patients on coumadin anticoagulant therapy, but does not appear to be a reliable measure of vitamin K status in otherwise healthy subjects. 

Oral anticoagulant therapy. Different procedures are inconsistently biased by the decreased y carboxylation of Protein C and the other vitamin K-dependent proteins... 

Anticoagulant therapy should be monitored carefully in patients with severe hepatic or renal failure, vitamin K deficiency, or alcoholism, and those with arthritis who are taking acetylsalicylic acid in large quantities. Furthermore, anticoagulants are extensively metabolized and their metabolites excreted, which can have an important bearing in patients suffering from renal disorders. 

Warfarin and other vitamin K antagonists have been the mainstay of oral anticoagulant therapy for... 

Johnson MA. Influence of vitamin K on anticoagulant therapy depends on vitamin K status and the source and chemical forms of vitamin K. Nutr Rev 2003 63,91-7... 

Cardiovascular Matrix Gla protein (MGP) has been previously described as an important inhibitor of vascular calcification, and inhibition of carboxylation of this enzyme by vitamin K antagonists has been associated with excessive coronary vessel calcification [1. In a case-control study in 19 Dutch patients aged under 55 years and 18 healthy age-matched controls, long-term coumarin anticoagulant therapy was strongly associated with femoral artery calcification (OR=8.5 95% CI=2.0, 35), and there was a strong correlation between coumarin use and plasma MGP concentrations [2. ... 

Warfarin has been the mainstay of oral anticoagulant therapy for many years, principally for atrial fibrillation, mechanical heart valves, or venous thromboembolism. Adverse-effects profile of patients on warfarin therapy parallel what would be seen in vitamin K deficiency. Dne to its inhibitory effect on VKOR in the liver, warfarin affects the fnnction of the MGP and has been associated with vascular calcification in various animal and human studies. 

The main way of determining vitamin K status, and monitoring the efficacy of anticoagulant therapy, is by measuring the time required for the formation of a fibrin clot in citrated blood plasma after the addition of calcium ions and thromboplastin — the prothrombin time. A more sensitive index is provided by direct measurement of preprothrombin in plasma, most commonly by immunoassay using antisera against preprothrombin that do not react with prothrombin. 

A number of adverse effects of excessive intakes of vitamin C have been reported, such as nausea abdominal cramps and diarrhea absorption of excessive amounts of food iron destruction of red blood cells increased mobilization of bone minerals interference with anticoagulant therapy formation of kidney and bladder stones the inactivation of vitamin B-12 a rise in plasma cholesterol and possible dependence upon large doses of vitamin C (small closes no longer meet nutritional needs). It is also noteworthy that undesirable side effects may be greater in certain physiological states (e.g. pregnancy). 

The exact mechanism of the interference of a-tocopherol with anticoagulant therapy is not known however, it may involve the blocking of the oxidation of vitamin K by vitamin E, thus decreasing the active form of vitamin K. Warfarin, which is a vitamin K antagonist, is also thought to decrease the active form of vitamin K [88],... 

Individuals who are deficient in vitamin K or who are on anticoagulant therapy are at increased risk of uncontrolled bleeding. Patients on anticoagulant therapy should be monitored when taking vitamin E supplements to ensure adequate vitamin K intakes. 

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