Vitamin K deficiency

The response of deficient animals to repletion with vitamin K, or the administration of the vitamin after anticoagulants, is more rapid than might be expected. There is a considerable intracellular accumulation of preprothrombin, whichis immediately available for carboxylation when vitamin Kbecomes available. 

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The classical method for the determination of vitamin K is based on the clotting time of a vitamin K-deficient chick. It is relatively easy to produce a hemorraghic state ia chicks (17). Vitamin K-deficient tats have also been used for this assay (18). Owiag to the development of modem chromatographic techniques, this method of analysis has been supplanted by other methodology. 

Owing to the ubiquitous natural occurrence of vitamin K and its production by intestinal bacteria, vitamin K deficiencies are rare. However, they can be caused by certain antibiotics (qv) coupled with a reduced dietary intake. Newborn infants who do not possess the necessary intestinal bacterial population are at danger for vitamin K deficiency. As a result, vitamin K injections are routinely given to the newborn. 

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. 

As the above mentioned studies with high supplementation dosages exemplarily show, there is no known toxicity for phylloquinone (vitamin Kl), although allergic reactions are possible. This is NOT true for menadione (vitamin K3) that can interfere with glutathione, a natural antioxidant, resulting in oxidative stress and cell membrane damage. Injections of menadione in infants led to jaundice and hemolytic anemia and therefore should not be used for the treatment of vitamin K deficiency. 

The salicylates are used cautiously in patients witii hepatic or renal disease, preexisting hypoprotiirombine-mia, or vitamin K deficiency and during lactation. The dragp are also used with caution in patients with gastrointestinal irritation such as peptic ulcers and in patients with mild diabetes or gout. 

Bile acid sequestrants may interfere with die digestion of fats and prevent die absorption of die fat-soluble vitamins (vitamins A, D, E, and K) and folic acid. When die bile acid sequestrants are used for long-term therapy, vitamins A and D may be given in a water-soluble form or administered parenterally. If bleedingtendencies occur as die result of vitamin K deficiency, parenteral vitamin K is administered for immediate treatment, and oral vitamin K is given for prevention of a deficiency in the futum... 

Prothrombin and several other proteins of the blood clotting system (Factors VII, IX and X, and proteins C and S) each contain between four and six y-carboxygluta-mate residues which chelate calcium ions and so permit the binding of the blood clotting proteins to membranes. In vitamin K deficiency or in the presence of warfarin, an abnormal precursor of prothrombin (preprothrombin) containing little or no y-carboxyglutamate, and incapable of chelating calcium, is released into the circulation. 

Deficiency of manganese may lead to vitamin K deficiency (Chiswell and Johnson 1994) and to problems in prenatal and neonatal development of the brain. 

Vitamin K is an essential factor in the production of coagulation proteins within the liver. Elevated clotting times from decreased protein synthesis are indistinguishable from those produced by low vitamin K levels caused by malnutrition or poor intestinal absorption. Vitamin K (phytonadione) 10 mg subcutaneously daily for 3 days can help to establish whether the prolonged bleeding time results from loss of synthetic function in the liver or vitamin K deficiency. 

Vitamin K is a fat-soluble vitamin cofactor for the activation of factors II, VII, IX, and X in the liver. Almost all neonates are vitamin K-deficient at as a result of (1) insignificant transplacental vitamin K crossover, (2) lack of colonization of the colon by vitamin K-producing bacteria, and (3) inadequate dietary vitamin K intake (especially in breast-fed infants because human milk contains less vitamin K than infant formula or cow s milk). Vitamin K-deficiency bleeding (VKDB) refers to bleeding attributable to vitamin K deficiency within first 6 months of life. It occurs in three general time frames early (0-24 hours), classic (1-7 days), and late (2-12 weeks). Early onset occurs rarely and usually is associated with maternal ingestion of anticonvulsants, rifampin, isoniazid, and warfarin. Classic vitamin K-dependent bleeding usually results from the lack of prophylactic vitamin K administration in... 

The main goal of treatment for vitamin K deficiency is prevention and control of VKDB. Specifically, therapeutic options may... 

Activated partial thromboplastin time aPTT is performed by adding calcium phospholipids and kaolin to citrated blood and measures the time required for a fibrin clot to form. In this manner, aPTT measures the activity of intrinsic and common pathways. Prolongation of aPTT may be due to a deficiency or inhibitor for factors II, V, VIII, IX, X, XI, and XII. It also may be due to heparin, direct thrombin inhibitors, vitamin K deficiency, liver disease, or lupus anticoagulant. 

Prothrombin time PT is performed by adding thromboplastin (tissue) factor and calcium to citrate-anticoagulated plasma, recalcifying the plasma, and measuring the clotting time. The major utility of PT is to measure the activity of the vitamin K-dependent factors II, VII, and X. The PT is used in evaluation of liver disease, to monitor warfarin anticoagulant effect, and to assess vitamin K deficiency. 

All-fraws-menaquinone-4, 191, potentially useful for therapy of hypoprothrombinemia due to vitamin K deficiency, has been synthesized162 using ethyl [3-14C]acetoacetate as shown in equation 69, for drug disposition studies in animals. 

To correct vitamin K deficiency in newborns, women should take 10 mg oral vitamin Kj daily during the last month of gestation. 

Primary vitamin K deficiency is uncommon, not only because of the presence of vitamin K in many plant and animal tissues but also due to its production by microorganisms in the intestine. Broad spectrum antibiotics, however, can lead to low levels of vitamin K due to loss of microorganisms in the intestine. Newborn infants can become deficient since it does not cross the placenta, hence... 

Vitamin K (phylloquinone) and similar substances with modified side chains are involved in carboxylating glutamate residues of coagulation factors in the liver (see p. 290). The form that acts as a cofactor for carboxylase is derived from the vitamin by enzymatic reduction. Vitamin K antagonists (e. g., coumarin derivatives) inhibit this reduction and consequently carboxylation as well. This fact is used to inhibit blood coagulation in prophylactic treatment against thrombosis. Vitamin K deficiency occurs only rarely, as the vitamin is formed by bacteria of the intestinal flora. 

VII, IX, and X when caused by vitamin K deficiency or interference with vitamin K activity. 

Enhanced anticoagulant effects Endogenous factors that may be responsible for increased PT/INR response include the following Blood dyscrasias cancer collagen vascular disease CHF diarrhea elevated temperature hepatic disorders (eg, infectious hepatitis, jaundice) hyperthyroidism poor nutritional state steatorrhea vitamin K deficiency. 

Chronic use of resins may be associated with increased bleeding tendency due to hypoprothrombinemia associated with vitamin K deficiency. 

Hepatic function impairment Use caution in liver damage, preexisting hypoprothrombinemia, and vitamin K deficiency. 

The absorption of vitamins K2, which are found mainly in cheese, curd cheese, and natto, is much higher and may be almost complete. Thus the nutritional importance of menaquinones is often underestimated. The vitamin K activity is related to the activation of specific proteins involved in blood clotting and bone metabolism. Clinical vitamin deficiency due to dietary inadequacy is rare or nonexistent in healthy adults, thanks to the widespread distribution of the vitamin K in foodstuffs and the microbiological flora of the gut, which synthesizes menaquinones. Only infants up to 6 months are at risk of bleeding due to a vitamin K deficiency. No data on negative effects of an overdose of vitamin K are found [417]. 

In normal individuals phytonadione and the menaquinones have no activity while in vitamin K deficiency the vitamin promotes the hepatic biosynthesis of factor II (prothrombin), factor VII, factor IX and factor X. Vitamin K functions as an essential cofactor for the enzymatic activation of precursors of these vitamin K dependent clotting factors. The quinone structure of the active form of vitamin K, i.e. reduced vitamin K or hydroquinone. 

Puckett RM, Offringa M. Prophylactic vitamin K for vitamin K deficiency bleeding in neonates. Cochrane Database Syst Rev 2000. 

The most common group of drugs that produce vitamin K deficiency are the coumarin anticoagulants. The hy-poprothrombinemic effects of dicumarol can be overcome by administration of vitamin K. 

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