3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.4. Physiology
                  3.1.4.4. Haematology
                      3.1.4.4.1. Haemostasis
 3.1.4.4.1.4. Vitamin K 

Vitamin K

[KB2:p206-207]

Function

Allows production of certain proteins

  • Clotting proteins that are vitamin-K dependent
    --> Factors 2,7,9,10, protein C and protein S
  • Bone protein
    * e.g. osteocalcin

Mechanism of action

Vitamin K is a cofactor for the enzyme (carboxylase) that catalyzes the conversion of glutamic acid residues to gamma-carboxyglutamic acid residues
* Vitamin K is oxidised during this reaction
* After this reaction, vitamin K needs to be reduced to become active cofactor again

Vitamin K allows for donation of a COOH group
--> Allows the clotting factor to bind to PF3 or TPL by a Ca2+ bridge

NB:

  • The conversion is an example of post-translational modification

Vitamin K intake

  • Dietary vitamin K
    * Absorbed from small intestine
    * Fat-soluble, thus require bile salt
  • Some vitamin K is produced by bacteria in terminal ileum and large amounts are produced in colon
    * But only vitamin K produced in terminal ileum is absorbed
    * Vitamin K produced from bacteria in colon is not absorbed

NB:

  • Vitamin K enters the circulation in chylomicrons in the lymphatics

Vitamin K in newborn

Newborn infants are vitamin K deficient because

  • Vitamin K does not cross the placenta in sufficient amount
  • Bacterial production of vitamin K in newborn does not occur in the first week of life
  • Dietary intake of vitamin K is poor
    * Breast milk has low levels of vitamin K

As a result
--> Haemorrhagic disease of the newborn

NB:

  • Phenytoin taken by mothers during pregnancy concentrates in the foetal liver
    --> Inhibits the action of vitamin K

Coumarin

Coumarin derivatives (e.g. dicumarol and warfarin)
--> Inhibits the reduction of vitamin K after it was oxidised during the conversion
--> Vitamin K cannot be recycled back into active co-factor

Vitamin K injection

Vitamin K injection is used to reverse the effect of warfarin
* Also come in tablets

  • If anticoagulation with warfarin is needed afterwards
    --> 1-2mg of vitamin K (IV)
    * 8-12 hours are required for the effect to set in 
  • If anticoagulation with warfarin is not needed
    --> 10mg of vitamin K
    * It is a very large dose
    * Warfarinisation is difficult after 10mg of vitamin K
  • Reversal of warfarin with vitamin K takes time
  • Fresh frozen plasma is used to quickly replace the clotting factors