Anticoagulation therapy

Anticoagulant drugs are conveniently divided into three main groups: orally active agents, heparin and thrombolytic agents. Oral coagulants themselves comprise two groups: the coumarins (warfarin, dicoumarol, nicoumalone, phenprocoumon and others) and the indanediones (phenindione, anisindione and others).

Warfarin sodium enjoys by far the most widespread clinical usage. presently the only anticoagulants available for oral use.

These compounds depress hepatic synthesis of the four vitamin K-dependente procoagulants (factors II, VII, IX, and X) and of two inhibitors (protein C and S).

The indications for long term prophylactic treatment is thromboemboly.

Patients receiving warfarin therapy should have frequent m

easurement of anticoagulation and this should be performed using the International Normalized Ratio (INR). Prothrombin time is no more indicated.

         Thromboembolic risk           

High, > 6% per year

Medium, 2-6%

Low, < 2%

Acute coronary syndrome

Vein grafts (1-3 months old)

Coronary intervention

Stable coronary artery disease

Vein grafts < 1 years old

Primary prevention of CAD

Anticoagulant + platelet

Inhibitor (PI)

Anticoagulant + PI


Mitral stenosis and Atrial fibrillation (AF)

Non valvular AF, anterior MI, LV disfunction

Mitral stenosis with normal rythm, Lone AF, Chronic LV aneurysm

AF + previous tromboembolism



INR 2.5-3.5

INR 2-3

No therapy

Old prosthetic valve

Prostetic valve and previous thromboembolism

Prosthetic valve, bioprosthetic valve early

Postoperatively or with AF

Bioprosthetic valve and Normal Sinus Rhythm

INR 3-4.5 or INR 2.5-3.5 + ASA

Mechanical = INR 2,5-3,5

No therapy


Warfarin has a relatively narrow terapeutic index. Because it is entirely metabolized in the liver patients with impaired hepatic function might be expected to increase sensitivity to the drug. The most serious risks associated with warfarin are hemorrhage in any tissue or organ, and less frequently, necrosis or gangrene of the skin and other tissues. Many drugs may affect the response to warfarin:

q       Increased response: acetaminophen, alcohol (acute), allopurinol, amiodarone, anabolic steroids, antiplatelets, cimetidine, clofibrate, co-trimoxazole, disulfiram, erytromicin, etacrynic acid, fluoroquinolones, glucagon, influenza virus vaccine, isoniazid, lovastatin, methylthiouracil, metronidazole, nalidixic acid, neomycin, NSAIDs, other anticoagulants, pentoxifylline, propafenone, propoxyphene, propylthouracil, quinidine, sulfonamides, tamoxifen, tetracycline, thyroid drugs, thrombolytics, tryciclic antidepressants, thiazides, vitamin E

q       Decreased response: alcohol (chronic use), aminoglutethimide, barbiturates, carbamazepine, cholestiramine, corticosteroids, corticotropin, estrogen-conteining products, glutethimide, marcatptopurine, methaqualone, nafcillin, rifampin, spironolactone, sucralfate, trazodone, vitamin K

Food: all food containing more than 100 mg vitamin K/100 g may decrease the anticoagulation response to warfarin, they include: broccoli, Brussels sprouts, green or white cabbage, cauliflower, kale, lettuce, soybeans, spinach, turnip greens, beef liver or kidney, and pork liver.

Contraindication: pregnancy, recent surgery or trauma involving brain, eye, or spinal cord, active major bleeding, blood dyscrasias, arterial aneurysm, severe hypertension, endocarditis, pericarditis, pericardial effusions, known hypersensitivity

      Antidote: vitamin K


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