Structural Biochemistry/Warfarin

Introduction
Warfarin is an oral anticoagulant to prevent new blood clots from forming. Blood clot is the aggregation of platelets in the blood vessels and the formation of fibrin network which traps the additional blood cells which can cause heart attack, stroke or other medical problems.

Warfarin also is used to treat venous thrombosis (which is the swelling and blood clot in a vein). It is used to prevent pulmonary embolism (blood clot in the lung). Warfarin also can be called anticoagulants ("blood thinners").

Coagulation
Blood coagulation is the process of formation of blood clots. It involves a series, known as the “coagulation cascade.” Each step of the cascade involves a protease, a zymogen, a non-enzymatic protein cofactor, platelets surface, and calcium ions. In each step, zymogen is converted to an active protease by cleavage of one or more peptide bonds in the zymogen. Thrombin is the last in a series of coagulation enzymes that are activated by proteolysis of zymogen. Thrombin then converts the soluble fibrinogen into insoluble fibrin, which eventually forms a fibrin meshwork and the ultimate blood clot.

Who needs Warfarin?
Patients with prosthetic heart valves, irregular heartbeat, thrombosis, and embolism are prescribed warfarin.

Overview
The chemical name of Warfarin is 4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-chromen-2-one, and the chemical formula is C19H16O4.

How it works
Warfarin is used to decrease the ability of clotting of blood. It works by inhibiting vitamin-K-dependent coagulation factors. It inhibits the production of clotting factors II, VII, IX, and X. These factors require carboxylation of glutamic acid residues to bind phospholipids to the factors, which is a vitamin-K-related process. After vitamin K is converted to vitamin K epoxide in the liver by oxidation, vitamin K epoxide is then reduced to vitamin K epoxide reductase (VKOR) by an enzyme. This reduced epoxide is necessary for the production of coagulation factors. Therefore, warfarin plays a role in prohibiting the actions of VKOR in the liver, so available amount of vitamin-K that can be used for oxidation and the production of coagulation factors is decreased.

Diet for patients taking warfarin
It is recommended to avoid food which is rich in vitamin K, for example, green leafy vegetables, liver, and vegetable oils.

How medicine works can be affected by the food people eat. Warfarin is a medicine prescribed for people with high risk of forming blood clots. It can prevent harmful blood clots, which may block the flow of blood to the heart or brain from forming. Vitamin K is a vitamin usually found in leafy green vegetables. In contract of Warfarin, vitamin K plays a major role in blood clotting in the body. It is used to reverse the effects of “blood thinning” medications like Warfarin. Warfarin decreases the activity of vitamin K and lengthening the time it takes for a clot to form. Therefore, in order to make warfarin work effectively, it is very important to keep vitamin K intake as consistent as possible. First, keep intake of high vitamin K foods consistent. Second, do not have large changes in the medium vitamin K foods intake. Third, be careful about dietary supplements. It is not wise to take vitamin E or fish oil supplements. Finally, dietitian or physician may restrict cranberry juice from your diet.

Side effects
Side effects include unusual bleeding, diarrhea, chest pain, face swelling, sudden headache or dizziness, severe leg pain, body discoloration, and purple fingers and toes.

Other side effects include change in the way things taste, tiredness, pale skin, loss of hair, or even feeling cold or having chills. Warfarin also may cause necrosis or gangrene, which means death of skin or other body tissues).