Warfarin is an age-old anticoagulant which has been in use since 1954. It inhibits the gamma-carboxylation of Vitamin K dependent clotting factors Ⅱ, Ⅷ, Ⅸ and Ⅹ. It takes about 72 hours after the initiation or change in dose of Warfarin for the maximum effect to be seen as factors already in circulation need to decay. Thus a patient who is started on warfarin will have the full expected effect in 72 hours (3 days).
INR (International Normalised Ratio) is a laboratory test that is used to measure the effect of the action of Warfarin.
The expected INR is usually given as a target INR. However, it can be expressed as a range of +/- 0.5. For example, target INR of 2.5 is usually given as a target range of 2 – 3.
Indications for anticoagulation
- Venous thrombotic events (Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE)), and Atrial Fibrillation (AF) are common indications for the use of anticoagulation.
- Patients with bioprosthetic heart valves need anticoagulation for only 3 months after surgery. However mechanical heart valves need long term anticoagulation and the target INR ranges from 2.5 to 3.5 depending on the type of valve thrombogenicity and patient risk factors.
- Sometimes anticoagulation with Warfarin may be initiated following Myocardial Infarction (MI) with an INR target of 2·5. Patients with dilated cardiomyopathy are anticoagulated to prevent systemic embolism and again target INR is 2·5.
Monitoring Warfarin therapy
Although a loading dose regime of 10mg, was practiced previously at Warfarin initiation, there is no evidence to suggest a 10mg loading dose is superior to a 5mg loading dose. Therefore lower dose Warfarin initiation is now practiced with dose escalation if appropriate INR has not been achieved.
The target range for INR for different clinical conditions varies but is usually between 2 – 3 or 2.5 – 3.5. The expected target range will be documented in the patients clinical notes by the cardiologist, physician or haematologist who follows up the patient. If high INR of over 4.0 are seen the patient is over anticoagulated and is at risk of bleeding. Inquire of any bleeding manifestations – haematuria, bleeding from gums, purpura and examine the patient for any skin bleeding. Ask about any drug or food interactions in the few days before that which may have led to the increase in INR.
Major bleeding is treated with 5mg intravenous vitamin K and prothrombin complex concentrate.1-3mg intravenous vitamin K is used for non‐major bleeding. Patients who are not bleeding but with an INR >5·0 should have 1-2 doses of Warfarin withheld and patients with an INR >8 and not bleeding should be given 1-5mg of oral vitamin K.
Drugs and food that cause increase/decrease in INR
The drugs and food that potentiate and inhibit the action of Warfarin are many. It is not possible to include a comprehensive list. The highly probable drugs/foods listed in literature are shortlisted below.
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