Vitamin K-dependent Coagulation Factors

The proenzymes, factors II, VII, IX, and X, require vitamin K for gammacarboxylation of their glutamic acid residues which allows these factors to bind calcium ions. Calcium ion binding alters the conformation of the gammacarboxyglutamic acid domain such that hydrophobic residues are exposed and able to bind to phospholipid membranes. This binding is necessary for coagulation to proceed. Vitamin K antagonists, such as coumarin-containing poisons and dicoumarol found in moldy sweet clover, prohibit gammacarboxylation of glutamic acid residues in these proenzymes and calcium binding does not occur.

Animals affected by these agents experience severe spontaneous hemorrhage that is typical of a disorder of secondary hemostasis. PT and PTT are usually greatly prolonged and treatment with vitamin K1, possibly together with blood or fresh plasma transfusion, is generally curative in patients presented at a sufficiently early stage of the condition. Vitamin K1 therapy is often required for at least one month following ingestion, particularly given the longer biological half-life of many of the newer coumarin-type products.

A hereditary vitamin K-dependent coagulopathy has been identified in Devon Rex cats. Clinical signs are variable but may involve hemorrhage following surgical procedures as well as spontaneous hemorrhage typical of a disorder of secondary hemostasis. PT and PTT are prolonged and concentrations of factors II, VII, IX, and X are reduced. The disorder is responsive to vitamin K1 therapy.