Vitamin K (phylloquinone): vitamin K deficiency

Vitamin K (phylloquinone) is a dietary vitamin K. Dietary fat enhances its absorption. Vitamin K supplements are added to infant formulas. Vitamin K is a group of compounds (menaquinones) synthesized by intestinal bacteria; the amount synthesized does not satisfy the need for vitamin K.

Vitamin K controls the formation of coagulation factors II (prothrombin), VII, IX, and X in the liver. Other vitamin K-dependent coagulation factors are proteins C, S, and Z; proteins C and S are anticoagulants. Metabolic conversions help conserve vitamin K; once vitamin K has participated in the formation of coagulation factors, the reaction product, vitamin K epoxide, is enzymatically converted to the active form, vitamin K hydroquinone.

The action of vitamin K-dependent proteins requires Ca. Vitamin K-dependent proteins, osteocalcin and matrix block containing y-carboxyglutamine protein, play important roles in bone and other tissues.

Vitamin K hypovitaminosis

Vitamin K deficiency results from extremely inadequate dietary intake, lipid malabsorption, or the use of coumarin anticoagulants. Deficiency is particularly common in breastfed infants. Hypovitaminosis K contributes to impaired blood clotting. The diagnosis can be suspected on the basis of standard blood clotting tests and is confirmed by the effect of vitamin K supplementation. Treatment consists of oral vitamin K. When the cause of the deficiency is lipid malabsorption or there is a high risk of bleeding, vitamin K is administered parenterally.

Vitamin K deficiency reduces levels of prothrombin and other vitamin K-dependent clotting factors, causing coagulation disorders and potentially bleeding.

Causes of Vitamin K Deficiency

Vitamin K deficiency can cause increased childhood illness and mortality worldwide. Vitamin K deficiency causes hemorrhagic disease of the newborn, which usually appears 1-7 days after birth. In these newborns, birth trauma can cause intracranial hemorrhage and bleeding. Newborns are prone to vitamin K deficiency because:

1. the placenta is relatively poor at passing lipids and vitamin K;
2. prothrombin synthesis in the still immature liver is imperfect;
3. breast milk has a low vitamin K content - approximately 2.5 mcg/l (cow's milk contains 5000 mcg/l) and
4. The intestines of newborns are sterile during the first few days of life.

Late hemorrhagic disease (3-8 weeks after birth) is usually associated with breastfeeding, malabsorption, or liver disease. If the mother has taken phenytoin anticonvulsants, coumarin anticoagulants, or cephalosporin antibiotics, the risk of developing both types of hemorrhagic disease is increased.

In healthy adults, dietary vitamin K deficiency is rare because vitamin K is widely distributed in green vegetables and bacteria in the intact intestine synthesize menaquinones. Biliary obstruction, malabsorption, cystic fibrosis, and small bowel resection contribute to vitamin K deficiency.

Coumarin anticoagulants interfere with the synthesis of vitamin K-dependent coagulation factors (II, VII, IX, and X) in the liver. Certain antibiotics (especially some cephalosporins and other broad-spectrum antibiotics), salicylates, vitamin E overdose, and liver failure increase the risk of bleeding in patients with vitamin K deficiency.

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Symptoms of Vitamin K Deficiency

Bleeding is the most common manifestation. Ease of bruising and bleeding of mucous membranes (especially nosebleeds, gastrointestinal bleeding, menorrhagia, and hematuria) are characteristic. Blood may leak from incisions or puncture sites.

In infants, hemorrhagic disease of the newborn and late hemorrhagic disease can lead to cutaneous, gastrointestinal, intrathoracic, and in the worst cases, intracerebral hemorrhages. In obstructive jaundice, bleeding - if it occurs - usually begins after 4-5 days. Bleeding may begin as a slow ooze from a surgical wound, gums, nose, gastrointestinal mucosa, or as a massive gastrointestinal bleed.

Hypervitaminosis (intoxication) of vitamin K

Vitamin K1 ₍ phylloquinone) is nontoxic when taken orally, even in large amounts. However, menadione, a synthetic water-soluble precursor of vitamin K, can cause toxicity and should not be used to treat vitamin K deficiency.

Diagnosis of Vitamin K Deficiency

Vitamin K deficiency or antagonism (caused by coumarin anticoagulants) may be suspected when abnormal bleeding occurs in patients at risk. Studies of the coagulation phases may provide preliminary support for the diagnosis. The prothrombin time (PT), now INR (international normalized ratio), is prolonged, but the partial thromboplastin time (PTT), thrombin time, platelet count, bleeding time, fibrinogen, fibrin degradation products, and D-dimer levels are normal. If PT is significantly reduced within 2-6 hours after intravenous administration of 1 mg phytonadione (an analogous name for vitamin K), liver disease is unlikely to be the cause, and the diagnosis of vitamin K deficiency is confirmed. Some centers can determine vitamin K deficiency more accurately by measuring plasma levels of the vitamin. Plasma vitamin K levels range from 0.2 to 1.0 ng/mL in healthy individuals consuming adequate amounts of vitamin K (50–150 mcg/day). Knowing the amount of vitamin K consumed can help interpret plasma levels; recent intake affects plasma but not tissue levels.

Currently, more sensitive indicators of vitamin K status are under study - PIVKA (Protein Induced in Vitamin K Absence or Antagonism) or immature (non-carboxylated) osteocalcin.

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Treatment of Vitamin K Deficiency

Whenever possible, phytonadione should be given orally or subcutaneously. The usual adult dose is 5-20 mg. (Rarely, even when phytonadione is properly diluted and given slowly, substitution for intravenous administration may result in anaphylactic shock or anaphylactic reactions.) The INR usually decreases within 6-12 hours. The dose may be repeated after 6-8 hours if the INR has not decreased sufficiently. Phytonadione 2.5-10 mg orally is given for the (non-emergency) correction of a prolonged INR in patients taking anticoagulants. Correction usually occurs within 6-8 hours. When only partial correction of the INR is desired (eg, when the INR must remain slightly elevated because of a prosthetic heart valve), lower doses (1-2.5 mg) of phytonadione may be given.

Infants who experience bleeding due to deficiency are given phytonadione at a single dose of 1 mg subcutaneously or intramuscularly to correct the bleeding. The dose is repeated if the INR remains elevated. Doses may be higher if the mother has been taking oral anticoagulants.

Prevention of Vitamin K Deficiency

Intramuscular administration of phytonadione 0.5-1 mg is recommended for all neonates within the first hour of birth to reduce the incidence of intracranial hemorrhage associated with birth trauma. This method is also used prophylactically prior to surgical interventions. Some clinicians recommend that pregnant women taking anticonvulsants also take phytonadione 10 mg orally once daily for 1 month or 20 mg orally once daily for 2 weeks prior to delivery. Because of the low vitamin K content of maternal breast milk, this can be increased by recommending up to 5 mg/day of phylloquinone in food.