Warfarin is a medical agent with anticoagulant properties. Mainly in the USA, it is used for the treatment of thrombosis. In Europe, phenprocoumon, a drug of the same class of active ingredients, is mostly used for this purpose.
What is warfarin?
Warfarin is a medical agent with anticoagulant properties. It is used to treat thrombosis. Warfarin belongs to the coumarin class of substances. Coumarins are present, for example, in various pasture plants. It was discovered that improper storage of hay during silage led to unstoppable bleeding in many grazing animals. This bleeding is due to the action of dicoumarol, which is formed by fungal attack of the hay. Based on this fact, the newly discovered substance was investigated for the possibility of medical use in the treatment of thrombosis. Three derivatives of dicoumarol were of interest, which came into medical use as anticoagulants under the names warfarin, phenprocoumon and tromexan. Previously, warfarin was used as a rat poison. After the rats ingested the poison with food, they died from internal bleeding, which occurred with a time delay.
Pharmacologic effect
Coumarins inhibit blood clotting by an indirect route. They act as an antidote (antitoxin) to vitamin K. Among other things, this vitamin controls the formation of various blood-clotting factors that take effect, for example, when blood leaks from the bloodstream through wounds. Coumarins, such as warfarin, interfere with the mode of action of vitamin K and thus prevent the formation of new blood clotting factors. However, the effect is delayed because clotting factors are still present and are only broken down slowly. After treatment with warfarin or other coumarin derivatives has been discontinued, it still takes some time for the usual concentration of blood clotting factors to be present again. This time is determined by the half-life of the degradation of the corresponding coumarins. In this context, warfarin has a half-life of 2 days, while phenprocoumon has a half-life of 10-14 days. This means that if warfarin is used after 2 days and if phenprocoumon is used after 10-14 days, normal blood clotting will resume. If rapid normalization of blood clotting is necessary, perhaps because an urgent operation is pending, vitamin K must be administered as an antidote to the coumarins. Because of the shorter half-life of warfarin, its use as an anticoagulant would be more appropriate than the use of phenprocoumon.
Medical application and use
The use of warfarin or other coumarins becomes necessary in severe cardiovascular disease where there is a concern for blood clot formation. This is done to dissolve existing thromboses to prevent the occurrence of a possible embolism. Such blood clots can lead to heart attacks, strokes or pulmonary embolisms. Prophylactically, warfarin is used in the case of upcoming operations or prolonged bedriddenness, in order to prevent the formation of thrombi and blood clots here. There are also conditions that require rapid treatment with warfarin or other coumarin derivatives, such as atrial fibrillation. This is a cardiac arrhythmia with a particularly high risk of embolism. In the case of existing thromboses, especially in the legs, anticoagulation (dissolution of the thrombi) is intended to prevent a recurrence of the thrombosis. In rare cases, lifelong treatment with coumarins is necessary, for example, in cases of repeated thrombosis or congenital blood clotting disorders. During treatment with warfarin, it is essential to ensure that as little vitamin K as possible is absorbed through the diet. As mentioned earlier, vitamin K acts as an antidote to warfarin and would neutralize its effectiveness.
Risks and side effects
Warfarin should not be used in conditions with an increased tendency to bleed, such as gastrointestinal bleeding, after surgery, or in liver or kidney disorders. As a side effect of treatment with warfarin, bleeding, hepatitis, jaundice, decrease in bone density or increased hair loss may occur. It should be noted that everyone reacts differently to warfarin, which is reflected in the different concentration ranges in which its anticoagulant effect unfolds.The limits of action are very narrow, whereby a concentration that is slightly too low can lead to ineffectiveness and a concentration that is slightly too high can, under certain circumstances, lead to severe bleeding. The limits of action depend on genetic conditions and the amount of vitamin K in the diet.
