Hemostasis is the arrest of bleeding when a small blood vessel is cut.

• Clotting factors and platelets are required for hemostasis.

• The major steps in hemostasis are

o Vascular response

o Platelet response

o Clotting response

o Permanent repair of the vessel wall

• Clotting response is initiated by the production of prothrombin Activator which

converts prothrombin into thrombin. For the production of the prothrombin

activator there are two major pathways intrinsic pathway and extrinsic pathway.

• Here for both pathways clotting factors are required.

• Vitamin K is fat soluble vitamin. Vitamin K can be intake via foods or can be produced

by gut micro flora.

• Vitamin K Is a cofactor for the enzyme that catalyzes the conversion of glutamic acid

residues to γ-carboxyglutamic acid residues.

• These proteins are factors II (prothrombin), VII, IX, and X, protein C, and protein S.

• Therefore, all six are vitamin K-dependent.

• The clotting factors bind to endothelium via calcium cross bridges.

• In order to form the cross bridges these clotting factors must be carboxylated.

• Upon adding the carboxyl group to glutamic acid residues on the immature clotting

factors, vitamin K is oxidized and becomes inactive.

• Another enzyme, vitamin K epoxide reductase complex 1 (VKOR c1), reduces vitamin

K back to its active form.(2)

• Coumarin derivatives prevent blood clotting by inhibiting the action of vitamin K.

• Warfarin causes this effect by inhibiting the enzyme VKOR c1

• By inhibiting VKOR c1, warfarin decreases the available active form of vitamin K in the

tissues.

• When this decrease occurs, the coagulation factors are no longer carboxylated and

are biologically inactive.

• So the warfarin therapy affects the both intrinsic and extrinsic pathways.

• This can lead to serious bleeding tendencies.

Reference :- Ganong's Review of Medical Physiology ( 26th edition )