Vitamin K

Vitamin K is an essential, lipid-soluble vitamin that plays a vital role in the production of coagulation proteins.

The reference range of vitamin K is 0.2-3.2 ng/mL, but impaired blood clotting has been associated with levels below 0.5 ng/mL by one source. ^[1] Another source cites a reference range of 0.10-2.2 ng/mL. ^[2]

Conditions associated with vitamin K deficiency include the following: ^{[3, 4]}

• Hemorrhagic disease of newborn

• Unexpected or excessive bleeding

• Osteoporosis (conflicting data ^[5] )

Conditions that may lead to vitamin K deficiency include the following: ^{[6, 3]}

• Chronic illness

• Malnutrition

• Alcoholism

• Multiple abdominal surgeries

• Long-term parenteral nutrition

• Malabsorption (cystic fibrosis, inflammatory bowel disease, cholestatic disease [biliary obstruction, primary biliary cirrhosis], celiac disease, chronic pancreatitis)

• Parenchymal liver disease

• Disseminated intravascular coagulation (DIC)

• Polycythemia vera

• Nephrotic syndrome

• Leukemia

Conditions associated with excessive vitamin K include the following: ^[1]

• Neonatal jaundice (with menadione [vitamin K3])

• Hemolytic anemia (with menadione [vitamin K3])

• Hyperbilirubinemia (with menadione [vitamin K3])

• Blockage of oral anticoagulants

Specifics for collection and panels are as follows: ^{[2, 7]}

• Specimen type: Blood serum or plasma

• Container: Vacutainer, plain red-top (serum) or lavender-top EDTA (plasma)

• Collection method: Venipuncture

• Specimen volume: 2 mL

• Rejected for hemolysis

Other instructions are as follows:

• Spin down and submit frozen in amber vial

• Fasting specimen

• No alcohol consumption for 24 hours before collection

The following are related tests:

• Prothrombin time (PT)

• Activated partial thromboplastin time (aPTT)

• Thrombin time

• Platelet count

• Platelet function tests

• Coagulation factors

• Fibrinogen

• D-dimer

Description

Vitamin K is an essential, lipid-soluble vitamin that plays a vital role in the production of coagulation proteins. There are 3 forms of vitamin K. Vitamin K1 (phylloquinone) is the natural form found in green, leafy vegetables; green tea; and oils such as soybean, cottonseed, canola, and olive oil. ^{[8, 9]} It is also the commercially available synthetic form used for treatment today. Vitamin K2 (menaquinone) is produced by colonic bacteria. Vitamin K3 (menadione) was a commercially available water-soluble form but is no longer available for use in humans because of toxicity. ^[1]

Vitamin K serves as a cofactor in the carboxylation of certain glutamic acid residues on precursor coagulation proteins. The carboxylation enables binding of these proteins to surface phospholipids to start the normal antithrombotic process. Osteocalcin, which is secreted by osteoblasts and plays a role in bone formation, undergoes vitamin K–dependent carboxylation in a similar fashion. ^{[5, 10]}

Vitamin K deficiency may affect any age group but is encountered most often in infancy. Infants with vitamin K deficiency—which may be caused by the limited transplacental transfer of vitamin K, the low level of vitamin K in breast milk, limited neonatal liver vitamin K storage, and low neonatal colonic bacterial colonization—are at risk for hemorrhagic disease of newborn. Newborns in the United States, Canada, and Great Britain are routinely given vitamin K to prevent this. ^{[5, 11, 12]}

Vitamin K toxicity is typically associated with formula or synthetic vitamin K3 (menadione) injections. Because of its toxicity, menadione is no longer used for treatment of vitamin K deficiency. ^[5]

Indications/Applications

Measurement of vitamin K is unusual because although the level responds to dietary changes within 24 hours, the effects on vitamin K–dependent proteins are delayed. If vitamin K deficiency is suspected in a patient with unexpected or excessive bleeding, PT is the main laboratory test indicated. If the PT is prolonged in such a patient, vitamin K is often administered. Cessation of bleeding and normalization of the PT after vitamin K administration is presumptive evidence of vitamin K deficiency. ^[1]

Considerations

Drugs that may cause vitamin K deficiency include the following: ^[1]

• Antibiotics (cephalosporins)

• Warfarin

• Salicylates

• Anticonvulsants

• Sulfa drugs

• High doses of vitamins A and E

• Bile acid sequestrants (cholestyramine, colestipol), mineral oils, and orlistat weight-loss medication (may decrease absorption of vitamin K)

Consensus recommendations from Belgium address the prevention of bleeding in infants due to vitamin K deficiency. These include, but are not limited to, the following ^[13] :

• It is recommended that at birth, all term neonates receive one 1 mg intramuscular (IM) dose of vitamin K. Parents who will not permit the IM injection should be informed by their healthcare providers of an alternative, albeit slightly inferior, regimen, in which 2 mg of oral vitamin K are administered at birth, with 1 or 2 mg of oral vitamin K subsequently given weekly for 3 months to breastfed infants. “No further supplementation is needed after birth in formula-fed infants,” however, and is also not needed in infants being fed with a combination of breast milk and formula once more than half of their intake consists of formula.
• To prevent coagulation disorders associated with vitamin K deficiency, infants with a fat malabsorption–associated disorder, such as cholestasis, require supplementation with vitamin K and other fat-soluble vitamins no matter which feeding mode is being used.