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Vitamin K

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Original Author(s): Lucy Ellis
Last updated: 8th April 2021
Revisions: 14

Original Author(s): Lucy Ellis
Last updated: 8th April 2021
Revisions: 14

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Vitamin K is one of four fat-soluble vitamins and has properties essential for blood coagulation and bone health. In this article we’ll be considering the synthesis, function and clinical significance of Vitamin K.

Synthesis

Vitamin K can be categorised into three main types: Phylloquinone (Vitamin K1), Menaquinone (Vitamin K2) and artificially synthesised Vitamin K.

Vitamin K1 is found predominantly in leafy green vegetables, such as spinach, brussels sprouts and broccoli. Vitamin K2 is seen in animal foods including meat, eggs and dairy.

Vitamin K is absorbed through the ileum and jejunum of the small bowel. As a fat-soluble vitamin, Vitamin K is carried through the enterocytes by a large fat goblet called a micelle. Here, it enters the bloodstream via the lymphatic system.  See the ‘Digestion and Absorption’ article for more detail.

Function

Vitamin K is essential for effective blood coagulation and plays a key role in synthesising certain clotting factors found in the clotting cascade. In the liver, it acts as a co-enzyme for γ-glutamyl carboxylase, an enzyme that converts the inactive forms of factors II (prothrombin), VII, IX and X into their active forms through the carboxylation of glutamic acid residues.

Vitamin K also helps synthesise Protein C and Protein S. These are important in the regulation of the clotting cascade by providing negative feedback in the form of anticoagulation.

Figure 1 – The clotting cascade

Vitamin K contributes to calcium metabolism. It is required for the synthesis of two regulatory proteins called osteocalcin and matix Gla-protein (MGP). Osteocalcin is produced by osteoblasts and encourages bone calcification, while MGP inhibits calcification of the blood vessels. By ensuring calcium stays in the bones, Vitamin K is thought to prevent the development of osteoporosis and cardiovascular disease.

Clinical Relevance

Vitamin K deficiency

Vitamin K deficiency can present with abnormal bruising, or frank bleeding. Causes include:

  • Malabsorption – Any condition that affects small bowel absorption e.g. Crohn’s disease, Ulcerative Colitis, short bowel syndrome, or antibiotic overuse resulting in destruction of the gut microbiome.
  • Inadequate intake – Specifically the foods mentioned above.
  • Vitamin K deficiency of the newborn – A combination of liver immaturity, a sterile gut microbiome and low-quality breast milk makes infants at higher risk of Vitamin K deficiency. This usually presents in days 2-4 of life but can occur up to two months in age, often with unexplained haemorrhage.

Vitamin K and Warfarin

Warfarin is an anti-coagulant that is used to prevent the risk of thromboembolism in certain patients. Warfarin competitively inhibits Vitamin K epoxide reductase complex 1 (VKORC1), an enzyme essential for the activation of Vitamin K in the body. By preventing the activation of vitamin K, the vitamin K dependent clotting factors (II, VII, IX, X) are inhibited and therefore clotting is inhibited too.

Patients taking warfarin are monitoring regularly using a blood test called the International Normalised Ratio (INR). The INR is calculated based on the ratio between the prothrombin times of the test and control samples.

If the INR is too high in a warfarinised patient and there is a bleeding risk, vitamin K can be given as a reversal agent, which is effective over a few hours. This works by overwhelming the warfarin within the bloodstream, and therefore supporting the production of vitamin K dependent clotting factors.

In an emergency section where there is life-threatening bleeding, prothrombin complex e.g. beriplex can be given for a rapid reversal of anticoagulation.

Figure 2 – A brain haemorrhage on a CT scan. This would be an indication for rapid reversal in someone taking warfarin

 

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