Friday 16 June, 2006
How to start warfarin therapy
Original article by: Michael Tam
Warfarin is an interesting medication – it saves many lives but causes many problems including some deaths of its own. At present, it is the only oral anticoagulant available in Australia and it is a commonly used drug. Warfarin management, however, is done notoriously badly in hospital.
The key to warfarin management is patience
The effective half-life ranges from 20 to 60 hours with a mean of about 40 hours (1). It takes around 3 half-lives to approach steady state and 5 half-lives to reach steady state. That is, for most patients it will take about a week before steady state is reached (and even longer for others). I have seen far too often in hospital people changing the dose of warfarin too rapidly with the result of the INR fluctuating up and down.
Step 1: Consent
Bleeding to death is a particularly unpleasant way to go and warfarin isn’t the safest drug if used inappropriately. Documented informed consent is necessary. Even better, arrange for a clinical pharmacist (if in a hospital) to counsel the patient on warfarin.
The annual incidence of fatality due to warfarin is oft quoted at around 1% though it is more likely to be around 0.2%. About 15% of patients have at least one minor bleed a year (2).
Step 2: Anticoagulation with heparin
Warfarin works by being an antagonist to vitamin K. Vitamin K is the cofactor in the production of the (not surprisingly named) vitamin K dependent clotting factors (Factor II, VII, IX and X). However, the anticoagulant enzymes Protein C and S are also dependent on vitamin K and have shorter half-lives than the clotting factors.
Thus, when you first start warfarin, there is a paradoxical initial pro-thrombotic effect. Other forms of anticoagulation are a necessity.
Usually, by the time a clinical decision is made to commence warfarin, the patient is already on unfractionated heparin (UFH) or low molecular weight heparin (LMWH). However, this is not always the case (for example, discovering that the cause of a stroke is paroxysmal atrial fibrillation) so always remembering to anticoagulate with UFH or LMWH first is important.
Step 3: Start warfarin
If a patient has previously taken warfarin and had been stable on a particular dose, then start with that dose. Otherwise, check their baseline INR and start:
warfarin 5 mg daily (nocte) for three doses
Step 4: Check INR on the morning of day 4 and adjust the dose
|INR (morning of day 4)||Change warfarin dose to|
|< 1.3||increase to 7 mg daily|
|1.3 – 1.7||continue with 5 mg daily|
|1.8 – 2.5||decrease to 3 mg daily|
|> 2.5||decrease to 1 mg daily|
Note: This is my personal opinion only – I do not believe in giving “loading doses” of warfarin. I believe that the dose of warfarin you should be giving is what you consider to be their “maintenance” dose in the longer term. There are other “initiation schemes” (here and here) that are designed for rapid attainment of the therapeutic level so the patient can be discharged earlier and come off other forms of anticoagulation.
Unfortunately, what commonly happens then is that the patient is discharged on much too high a dose with a high INR in 1-2 weeks time; much to the annoyance of the general practitioner, potentially risking a serious bleed in the patient, and will come back to bite you in the buttocks if they get readmitted.
Step 5: Stop heparin when INR reaches therapeutic levels
Some institutions would advocate daily INR tests until it reaches a therapeutic level (INR between 2.0 and 3.0). When the INR is 2.0 or above, the UFH or LMWH can be ceased and the patient discharged (if medically appropriate).
Some areas have an outpatient team that can warfarinise a patient at home. They have daily blood tests and a doctor calls them for their next dose of warfarin. A community nurse usually helps administer a LMWH like enoxaparin (Clexane) subcutaneously at home.
Step 6: Regular INR checks
Once the warfarin level is therapeutic, INR need only be performed every 1-2 weeks initially for a new patient. Changes in the dosage of warfarin should be to what is estimated as the maintenance dose. The practice of deliberate under or overdosing to more “quickly” reach the desired level should be avoided.
Remember that most GPs would only do the INR fortnightly.
For a stable patient, the INR needs only be performed perhaps once a month.
Step 7: Continuing warfarin education
It is important to educate and remind patients about warfarin – usually done by the general practitioner but it should be addressed for patients who are on warfarin and admitted to hospital. Medication compliance, education on diet (e.g., eating consistent amounts of vitamin K rich foods), drug interactions, avoiding unnecessary over-the-counter “vitamin” pills are all significant issues in the longer term management of a patient on warfarin.
Hints and tips
- Be aware that there are two brands of warfarin in the Australian market, Coumadin and Marevan. Unfortunately, they are not bioequivalent. The public NSW Health system only uses Coumadin. Though perhaps not particularly fair on the company that makes Marevan, I advocate using only Coumadin as it causes less confusion when the patient is admitted to hospital.
- Many patients can’t remember their dose, but remember the colour tablets that they are on. For Coumadin:
- 1 mg tablet = light tan
- 2 mg tablet = lavender
- 5 mg tablet = green
- If the patient is on a “3 mg tablet” of warfarin, then they are on Marevan:
- 1 mg tablet = brown
- 3 mg tablet = blue
- 5 mg tablet = pink
- Half milligram doses are difficult for the elderly as they may not have the manual dexterity to break or cut a tablet in half. Consider alternate day full milligram doses instead (e.g., rather than 4.5 milligrams daily, 4 milligrams and 5 milligrams alternate days).
- A pill box or blister pack and help many people stay compliant on their warfarin (and other medications as well).
- It is useful to have a good grasp on when and how to reverse warfarin when there is a high INR result (3).
A useful resource – an estimate of the final maintenance dosage of warfarin after commencing on 4 consecutive days of 5 mg daily dose (4):
|INR (morning of day 5)||Warfarin dose per week|
(1) Coumadin (warfarin sodium), MIMS, 1 April 2006.
(2) David A Fitzmaurice, Andrew D Blann, Gregory Y H Lip. Bleeding risks of antithrombotic therapy (ABC of antithrombotic therapy). BMJ 2002;325:828-831 (12 October) [download PDF :: 258 Kb]
(3) Tam M. How to reverse warfarin [electronic article]. The Medicine Box. Last updated 23 June 2006. [Link]
(4) Pengo V, Biasiolo A, Pegoraro C. A simple scheme to initiate oral anticoagulant treatment in outpatients with nonrheumatic atrial fibrillation. Am J Cardiol 2001;88:1215.
Updated: Michael Tam (20 July 2006)