Observations of hemorrhagic symptoms in study animals (chickens) maintained on diet to detect
sterol metabolism reported by a Danish scientist Henrik Dam in 1929, spurred studies to identify
an anti-hemorrhagic agent responsible for coagulation. This anti-hemo rrhagic agent later came to
be recognised as Vitamin K and Phthiocol, a form of Vitamin K (VK) became the first to be used in
human medicine. Though it is a very vital and indispensible nutrient for clotting, the amount required
in human body is very less. Hence, occurrence of deficiency is a very rare scenario. The deficiency,
if at all, occurs, is generally due to inadequate dietary intake, intestinal disorders, malabsorption
and to some extent decreased production by normal gut flora and renal failure. The use of vitamin
K antagonists, severe liver damage, fat malabsorption, Inflammatory Bowel Diseases and cystic fibrosis
increase the risk of acquiring vitamin K deficiency in adults. Newborn babies are born with a very low
content of vitamin K due to lack of bacteria in their gut, thereby leading to severe internal bleeding
cases. The incidences of late onset vitamin K deficiency characterised by unexpected episodes of
bleeding in infants between 2 - 12 weeks of age with inadequate neonatal vitamin K prophylaxis,
ranges from 4.4 to 7.2 per 1,00,000 infants.
Individuals who have experienced stroke, cardiac arrest and prone to blood clotting should
avoid taking vitamin K supplements
KOAGULATIONS-VITAMIN
Vitamin K is an anti-hemorrhagic factor, where K stands for "Koagulations-Vitamin", a
German word. It denotes a series of lipophilic and hydrophobic compounds with a common
2-methyl-1,2-naphthoquinone nucleus differing in side chain structures at position 3. Based
on the side chains, vitamin K is classified into three types: Vitamin K1 (Phylloquinone), the
major circulating form obtained from plant source; Vitamin K2 (Menaquinone) obtained from
bacteria and Vitamin K3 (Menadione), a synthetic form made for use in supplements. This is
generally recommended in cases wherein deficiency is triggered due to malabsorption and is
contraindicated for use in infants. Vitamin K acts as a cofactor for the enzyme y-glutamyl carboxylase
that catalyses carboxylation of glutamate (Glu) to gg-carboxyglutamate (Gla) and is linked to
a cyclic salvage pathway known as Vitamin K epoxide pathway wherein vitamin K is reduced and
recycled again. Vitamin K-dependent proteins interact with calcium ions which bind to membrane
proteins forming a protein-membrane complex. The calcium ion activates the clotting factors
comprising of factors II, VII, IX and X in the liver to induce coagulation. Apart from coagulation
proteins, vitamin K-dependent proteins have also been isolated from the bone, cartilage, kidney,
lungs and other tissues. Although, the presence of vitamin K in synthesis of bone proteinosteocalcin
is not confirmed, its levels greatly affect lipid metabolism and blood coagulation; making it a vital
component for body homeostasis.
Vitamin K Deficiency
In infants In 1894, Dr. Townsend, a physician from Boston described 50 cases of bleeding in
newborns; calling it "Haemorrhagic Disease of the Newborn' (HDN). By 1999, HDN was changed
to vitamin K deficiency bleeding (VKDB), wherein, there is a sudden brain haemorrhage in babies
without warning, as a result of less than sufficient levels of vitamin K. Two types of vitamin K
deficiency include:
Idiopathic vitamin K deficiency bleeding - The cause of the disorder is unknown and is often seen
in cases wherein the baby is breastfed.
Secondary vitamin K deficiency bleeding - Caused by underlying disorders such
as gallbladder disease, cystic fibrosis or side effects of medication.
Vitamin K deficiency bleeding follows three patterns of occurrence: Early, Classical and Late.
Early - occurs within the first 24 hours of life in
babies born to mothers on medication for seizure,
tuberculosis and heart attack (E.g. Coumadin).
Classical -occurs within 24-48 hours of life wherein the
vitamin K levels are the lowest. The official cause of classical vitamin K deficiency bleeding is unknown, but poor
breastfeeding is touted to be the major risk factor.
Late - occurs after the first week of life, especially between 3-8 weeks. Bleeding often happens
in the brain, skin and the gastrointestinal tract. Bleeding in the brain is the first sign of late
vitamin K deficiency bleeding and occurs in breastfed infants. Gallbladder disease, cystic fibrosis, chronic diarrhea and
antibiotic use are the major risk factors.
Vitamin K dependent coagulation factor deficiencies (VKCFD)
Apart from the above mentioned, an additional rare autosomal recessive bleeding disorder;
VKCFD causes severe hemorrhage during infancy. A mutation in the gene encoding for g-glutamyl
carboxylase causes defective y-carboxylation of anticoagulant proteins termed as VKCFD-I, whereas
a heterozygous defect in vitamin K epoxide reductase (VKOR) gene causes VKCFD-II, stalling the
Vitamin K metabolic pathway. This heritable dysfunction of g-glutamyl carboxylase or VKOR gene
results in secretion of poorly carboxylated vitamin K dependent proteins which play a role in
coagulation.
In infants, the most popular causes for deficiency are - absence of gut bacteria, low transmission
of Vitamin K across the placenta, Vitamin K deficiency in breast milk, etc.
In adults
Vitamin K is found in most
of the food sources as also the gut bacteria can synthesise the same. It is conserved by the epoxide
(oxidation-reduction) cycle thus, making the prevalence of vitamin K deficiency uncommon in adults.
However, deficiency of the same is observed in people suffering from:
Parenchymal liver diseases - Viral hepatitis
causing cirrhosis, hepatic malignancy, amyloidosis, Gaucher disease (sphingolipids accumulate in
cells and certain oreans) and other infiltrative disease. adversely affect the synthesis of vitamin K
dependent factors. Thus, vitamin K supplements prove to be ineffective unless the patient suffers
from severe bleeding and plasma transfusion is conducted to correct the coagulation disease.
Malabsorption syndrome - Vitamin absorption in ileum is affected; disease
like celiac sprue (glutensensitive enteropathy), tropical sprue (inflammation of the lining of small
intestine) and short bowel syndrome, etc. leading to multiple abdominal surgeries decrease vitamin K uptake
Biliary disease - Duct obstruction due to stones and
structural abnormalities cause diseases like cholangiocarcinoma, biliary cirrhosis and chronic
cholestasis which results in poor fat digestion and decrease in fat soluble vitamins, such as
vitamin K. Conditions like T-tube drainage of bile duct and surgery decreases the vitamin levels.
Dietary deficiency - Conditions like malnutrition and alcohol abuse trigger K
deficiency. A large amount of vitamin E can adversely affect functions of vitamin K and prolong
prothrombin time (blood tests which measures the blood clotting time).
Drug intake - Drugs like cholestyeramine that binds
to bile acids, prevents absorption of the fat-soluble vitamin. Coumadin (drug used to prevent
heart attack) blocks the effect of vitamin K epoxide reductase inducing an intracellular deficiency.
Vitamin K Food source and Dietary needs
The best way to overcome the deficiency and fulfill the daily requirement of vitamin K is through
food sources. The various sources included .
Plant source - Green leafy vegetables like spinach, kale, cabbage, broccoli,
avocado, banana, cauliflower contain 400-700ug/100g of vitamin K; edible vegetable oils like
soybean, rapeseed, olive contain 50-200 g/100g peanut, corn, sunflower and safflower contain
1-10 ug/100g.
Animal source - Fish liver, meat, eggs, cereals, milk
(1-4 ugl) and fermented food sources like cheese, as also the human body itself produces
vitamin K through bacteria in the colon.
Vitamin Facts
Vitamin K improves bones health and reduces risk of bone fractures.
Vitamin K Diagnosis and Treatment
Bleeding disorder is the primary indication for vitamin K deficiency. To differentiate bleeding related
to K deficiency and hepatic failure, the patient's factor V levels are estimated; factor V being
synthesised by the liver and not by vitamin k-dependent factor is the key for diagnostic insight.
The approach to correct the deficiency relies on the nature of the bleeding.
Vitamin K Pathology Test include
Prothrombin Time and Partial Thromboplastin
Time (PT and PTT) levels
The levels of PT and PTT are generally recommended for analysis, wherein the levels of PT are
elevated while PTT remains normal in cases of
severe Vitamin K deficiency
Des-gamma-carboxy prothrombin (DAS) levels
Des-gamma-carboxy prothrombin (DCP) is a "protein induced by vitamin K absence/antagonist-II
(PIVKA-II), and is the most sensitive marker,
elevated in Vitamin K deficiency.
A hematologist aids in interpreting the laboratory test results. When the hematologic or dietary
causes of Vitamin K deficiency are excluded, a gastroenterologist is consulted to diagnose liver disease,
malabsorption, etc. that can cause Vitamin K deficiency. In case of infants, the vitamin K injections have
been associated with childhood leukemia and other forms of cancer, thus making it a disputable
decision. Although, lately the vitamin K prophylaxis has outweighed the K deficiency's association
with childhood cancer and vitamin K1 recommendation for all neonates was brought into action.
It is now universally accepted that all infants should be given prophylaxis with vitamin Kat birth
in order to prevent severe deficiency disorders.
Treatment involves administering VK-1
subcutaneously or intramuscularly and monitoring PT levels. Also, oral form of Vitamin K is recommended
in varying doses (5-20mg) depending on the severity of the deficiency. The
treatment also bears with it some risks of toxicity associated with formula-fed infants or
synthetic menadione injections, which are no longer used to treat Vitamin K deficiency. Toxicity causes
a jaundice like condition in infants and is known to block the effects of oral anticoagulants.
Lack of vitamins in the body causes various complicated health disorders that impair the quality
of life of an individual. Vitamin K deficiency gravely affects infants, who are the future! If not
diagnosed and treated, it proves to be life-threatening. Thus, along with awareness for the
necessity of vitamins; the microessential nutrients, details of its diagnosis and sources spreads
an understanding towards inculcating a nutritious lifestyle. These irreplaceable essentials need
attention for a healthy life!
