ROLE OF VITAMIN K IN PAEDIATRIC PRACTICE
Pradipta Kumar Swain, Dept. of Paediatrics. Manipal College of Medical Sciences. Phulbari, Pokhara, Nepal.
Address for Correspondence: Pradipta Kumar Swain, Dept. of Paediatrics. Manipal College of Medical Sciences. Phulbari, Pokhara, Nepal. E-mail – firstname.lastname@example.org Vitamins belonging to the K group are polyisoprenoid-substituted napthaquinones. Three types of Vitamin K are available. Vitamin K3 (menadione) if administered is assimilated in vivo to Vitamin K2 (Menaquinone) which is also synthesized in the large gut by bacterial flora. It is used prophylactically in neonates and also in obstructive jaundice, fat malabsorption and celiac disease. Vitamin K is also has important role vascular biology, bone metabolism and blood coagulation. Vitamin K denotes a group of lipophilic and hydrophobic vitamins that are needed for the post translational modification of certain proteins, mostly required for blood coagulation. Chemically they are 2-methyl 1,4 -napthaquinone derivatives. The "K" is derived from the German word "koagulation". SOURCE & TYPESSources of vitamin K are divided into two groups:
Vitamin K1 (phylloquinone)
Vitamin K2 (menaquinone-n/MK-n), where n stands for the number of 5-carbon units synthesized in the large gut by flora. Vitamin K is found in leafy green vegetables such as spinach, lettuce, cabbage, cauliflower, broccoli, kiwifruits, meats, soyabeans, and cow’s milk. Vitamin K1 is the major dietary form of vitamin K. Vitamin K2 is found in chicken egg, butter yolk & cheeses.
Synthetic - Vitamin K3, menadione, is a synthetic form of this vitamin which is man made. PHYSIOLOGY
Absorption of vitamin K requires bile salts except K3.
Many bacteria such as E.Coli found in the large intestine can synthesize Vitamin K2
Crosses placenta very poorly as evidenced by the concentration of vitamin K in mothers’ serum (1-2 microgram/L) and cord blood (0.05 microgram/L).
This nutrient can be destroyed by freezing and radiation as well as air pollution.
Absorption may be decreased when rancid fats are present, as well as excessive refined sugar, antibiotics, high dosages of vitamin –E or calcium and mineral oils. FUNCTION
Generation of biologically active clotting factors involves post translational modification of glutamate (Glu) residues of precursor proteins to gamma-carboxyglutamate(Gla) residue by a specific Vitamin K dependent protein carboxylase. This reaction occurs in the endoplasmic reticulum of liver where inactive form of vitamin K (quinone) is again converted to active form (hydroquinone) by 2.3.epoxide reductase. This is known as Vitamin K cycle in liver.
Gla-residues are usually involved in binding calcium. 14 human Gla-proteins have been discovered, and they play key roles in the regulation of following three physiological processes: (1)
Blood coagulation (Factor-II, VII, IX, X, protein-C, protein-S, protein-Z)(2)
Bone metabolism (3)
Vascular biology (4)
It is also involved in bone formation and repair (Role in synthesis of osteocalcin).
In the intestines it also assists in converting glucose to glycogen, this can then be stored in the liver (6).
Gas6 is a vitamin K-dependent protein that has been found throughout the nervous system, as well in the heart, lungs, stomach, kidneys, and cartilage. Gas6 appears to be a cellular growth regulation factor with cell signaling activities. It may also play important roles in the developing and aging nervous system (7).
ROLE IN DISEASE
Vitamin K-deficiency may occur by disturbed intestinal uptake (in a bile duct obstruction), by therapeutic or accidental intake of vitamin K-antagonists or, very rarely, by nutritional vitamin K-deficiency. As a result of the acquired vitamin K-deficiency, Gla-residues are not or incompletely formed and hence the Gla-proteins are inactive. Lack of control of the three processes mentioned above may lead to the following:
Risk of massive, uncontrolled internal bleeding,
Cartilage calcification and severe malformation of developing bone, or
Deposition of insoluble calcium salts in the arterial vessel walls.
RECOMMENDED DAILY ALLOWANCE (RDA): - It is usually 1 microgm./kg/day (5)
Vitamin K concentration in Milk
Artificial milk powder
In every newborn at birthNewborn babies that are exclusively breast-fed are at increased risk of vitamin K deficiency for the following reasons:
Human milk is relatively low in vitamin K compared to formula,
The newborn's intestines are not yet colonized with bacteria that synthesize menaquinones
The vitamin K cycle may not be fully functional in newborns, especially premature infants.
Infants whose mothers are on anticonvulsant medication to prevent seizures.Parental dose = 1 mg intramuscularly (>34 weeks of gestation babies) 0.5 mg intramuscularly (< 34 weeks of gestation babies). Oral dose = 1-2 mg single dose to prevent only early & classic Hemorrhagic disease of newborn [HDN] (8) and on day 1, day 3, day 7 & then monthly upto 3 months in late HDN. In addition to the above prophylaxis following infants require continuation of vitamin K administration:
Alpha-1 antitrypsin deficiency.
Hemorrhagic disease of newborn
Oral anticoagulant overuse.
Rat poison ingestion (Dicoumarol type). Dose = 1-2 mg./kg/dose 6- 12 hourly, SC/slow IV according to prothrombin time (9). Precaution Patients having vitamin K deficiency bleeding (VKDB) otherwise known as HDN it should not be given IM route because of production of large hematomas at the site of administration.
Practically Vitamin K is non toxic. Therefore overdose of vitamin K is harmless. Sometimes rapid IV administration produces anaphylactic reaction & hemolysis. The same is not true for menadione (vitamin K3) and its derivatives. Menadione can interfere with the function of glutathione, one of the body's natural antioxidant resulting in oxidative damage to cell membrane. Menadione given by injection has induced liver toxicity, jaundice and hemolytic anemia (due to the rupture of red blood cells) in infants, and is no longer used for treatment of vitamin K deficiency (10).
Large doses of vitamin A and vitamin E have been found to antagonize vitamin K. Excess vitamin A appears to interfere with vitamin K absorption, while a form of vitamin E (tocopherol quinone) may inhibit vitamin K-dependent carboxylase enzymes (11). Oral anticoagulant action is inhibited by high dose of vitamin K.
VITAMIN-K DEFICIENCY STATES
Use of antibiotics for sterilization of gut
Disease with endogenously produced coagulation inhibitors, such as lupus anticoagulant and antithrombins and paraproteinemias, i.e., multiple myeloma, may cause a Vitamin K deficient state.
Miscellaneous causes include massive transfusion, disseminated intravascular coagulation (DIC), polycythemia Vera, nephrotic syndrome, cystic fibrosis, and leukemia.
Parenchymal liver diseases such as cirrhosis secondary to viral hepatitis, and other infiltrative diseases; hepatic malignancy; amyloidosis; Gaucher disease; and others decrease the synthesis of Vitamin K-dependent factors.
Vitamin K was discovered in relation to bleeding neonates (HDN) the incidence of which without vitamin K prophylaxis was 4-10/1000 live births. Hence it is known as the anti-hemorrhagic vitamin (12) and irrespective of sex, gestational age & cultural practices every newborn has a right to a dose of anti-hemorrhagic vitamin at the time of birth. Role of vitamin-K beyond neonatal period is coming up with development of its different actions at the cellular level like in osteoporosis, fracture, and vascular thrombosis.
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Last Updated On : 1st October 2007