Vitamin K1 is essential for normal blood coagulation.
Coagulation factors II, VII, IX and X and the anticoagulant proteins C and S are synthesized mainly in the liver and are biologically inactive unless 9 to 13 of the γ-amino-terminal glutamate residues are carboxylated to form the Ca2+-binding γ-carboxyglutamate residues.
This reaction requires carbon dioxide, molecular oxygen and reduced vitamin K, and is catalyzed by γ-glutamyl carboxylase in the rough endoplasmic reticulum.
Carboxylation is directly coupled to the oxidation of vitamin K to its corresponding vitamin K epoxide or oxidized vitamin K.
For the continued synthesis of activated clotting factors, vitamin K1 must be regenerated from the biologically inactive epoxide by vitamin K1 epoxide reductase.
Acenocoumarol and the coumarin anticoagulants are structurally similar to vitamin K and competitively inhibit the enzyme vitamin K-epoxide reductase. Hence, they are called vitamin K antagonists.
These drugs exert their anticoagulant action by preventing the regeneration of reduced vitamin K by interfering with action of vitamin K epoxide reductase.
Oral anticoagulants have no effect on the activity of fully carboxylated molecules in the circulation. Thus, the time required for the activity of each factor in plasma to reach a new steady state after therapy is initiated or adjusted depends on its individual rate of clearance. The approximate half-lives of these factors (in hours) are shown below
Half-lives of clotting factors inhibited by coumarins