Efficacy of warfarin is determined by the attain and maintaining an INR (International Normalized Ratio) with a narrow range of usually 2-3. This requires consistent blood monitoring. INR is essentially a measure of how quickly blood will clot.
The unit Warfarin: The Fundamentals discusses the mechanism of action and drug interactions of warfarin in more detail.
Despite the availability of newer anticoagulants that offer the ease of standard dosing warfarin remains the drug of choice in specific patients where cost, renal function and specific diagnoses prevent the use the newer direct acting oral anticoagulants (DOAC). Because of this we need to know how to dose warfarin.
Patient Considerations
It takes a responsible patient to use warfarin correctly. A thorough social history is needed so that we can identify patients whose lifestyle would place them at risk of using warfarin incorrectly.
Patients with active drug use, cognitive problems, homelessness are likely to be inconsistent with their medication.
Patients must have reliable ways of getting to INR testing sites and to general medical care because of the increased risk of bleeding which needs to be addressed quickly.
The concern is both for efficacy and the adverse outcomes that can result from improper use and monitoring.
This article provides a deeper dive into the psychosocial issues that must be considered with the use of warfarin.
Dosing Considerations
If it hasn’t been made clear by now, warfarin is not a standard drug. Both dose and the corresponding INR can vary largely with each patient. Achieving steady state is vital in patients on warfarin because the drug is effectively offering no protection if we are below INR range. It is crucial to always keep this in mind. Don’t be too conservative with dosing that you effectively do not treat.
If INR is above the recommended range, the patient is at an increased risk for bleeding. Don’t be too aggressive either!
There are general dosing recommendations that should be considered so that there is a systematic and justifiable approach to initiating and adjusting doses.
I recommend the use of a dosing nomogram, knowing always that it is just the baseline from which you will adjust based on patient specifics.
Patient Specifics
Most nomograms provide recommendations based on an otherwise healthy patient. The usual initial dose is 5mg once daily. Starting with this initial dose we will then consider our patients characteristics and determine if we need to increase or decrease this initial dose.
I. Age:
Patients who are elderly (>65 year old) will typically start at half the dose (2.5mg).
Elderly patients have a higher risk of hemorrhagic events with anticoagulation. Starting a lower dose allows us to titrate to goal while minimizing that risk.
II. Nutritional Status:
Patients who are malnourished are at an increased risk of bleeding with warfarin.
Serum albumin levels are used as an assessment of nutritional status in clinical practice. Low serum albumin indicates malnutrition.
Over 90% of warfarin absorbed is bound to albumin. Only unbound warfarin is active and available for vitamin K antagonism. When serum albumin is low, a greater portion of absorbed warfarin exists in its active from, increasing the risk of bleeding.
In malnourished patients it would be wise to lower the starting dose.
III. Comorbidities:
The 5mg starting dose of warfarin is recommended in patients who are, other than their need for anticoagulation, considered healthy.
In patients with liver disease, kidney disease, heart failure, cancer (to name a few) it maybe wise to start with a lower initial dose to minimize the risk of bleed. In patients with significant comorbidities there is a high rate of mortality in the event of a bleed.
IV. Drug Interactions
A complete medication review must be done for all patients started on warfarin. Some drugs can induce the metabolism of warfarin. This will reduce the anticoagulant effect and may require a high initial dose to get patient to goal.
Other medications by inhibit the metabolism of warfarin thus enhancing the anticoagulation effect and increasing the risk of bleed. These patients would require lower starting doses.
Other drugs may themselves have effects on coagulation that would add to that of warfarin, increasing the risk of bleed. The unit Warfarin: The Fundamentals covers drug interactions with warfarin in great detail.
All of these patient specifics must be weighed against any dosing nomogram. In most cases, your facility will have a protocol (their vetted nomogram) to guide dosing. The nomogram does not replace your clinical judgement.
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Timing of Dose Changes
Once we’ve decided in an initial dose of warfarin (standard, lower or higher) we then need to consider the timing of INR monitoring and dose adjustment.
Patients newly started on warfarin, especially in the inpatient setting will have daily INR levels. We want to identify any abnormal increases in INR that will place the patient at an increased risk of bleed.
An increase in INR greater than 0.3 units in one day is not favorable. We would need to reduce the current dose to prevent overshooting our goal.
The Third Dose
The INR after the 3rd dose of warfarin is an important check point. On day 3 of consistent dosing we can make predictions about what the full effect of the current dose will look like in a few days.
We use the INR on day 3 to decide whether the current dose needs to be increased, decreased or stay the same.
An INR<1.5 after 3 days of consistent dosing requires a increase in dose.
An INR >2 after 3 days of consistent dosing requires a decrease in dose.
An INR between 1.5-2 after 3 days of consistent dosing requires no change in dose.
Why 3 days?
Why would we decrease the dose if INR is within goal on day 3?
Warfarin works by inhibiting the production of clotting factors. It has no effect of clotting factors that were already produced prior to the initiation of warfarin. It does not destroy existing factors.
The longest half life of the the clotting factors affected is 72 hours (3 days): factor II. This means that it will take 3 days for any factor II that existed prior to warfarin to fall to just half of its concentration.
The full anticoagulant effect of warfarin will be seen when ALL the preexisting clotting factors have run their course. This will take ~ 5 days. If it is already therapeutic at day 3, it will be supratherapeutic on day 5 when all those preexisting clotting factors are depleted.
D1-D3 warfarin is anticoagulating while the preexisting clotting factors continue to coagulate and therefore affect INR. On D3-D5 there is still some coagulation by clotting factor II while warfarin is anticoagulating. Both warfarin and clotting factors continue to influence INR. After day 5, the only contributor to INR is the anticoagulation effect of warfarin.
INR is a Lag Value
An INR drawn today reflects the effect of the doses given on the prior 3-4 days. For example, if a patient has been on 5mg of warfarin with an subtherapeutic INR we can increase the dose to 7.5mg daily.
We would need 3-5 days of consistent dosing to see the effect of the dose change. Analysis of INR must always be down with consideration of prior dosing. During that time levels may still be drawn to trend the effect of the dose change and identify any jumps in INR that that suggest we may overshoot our target.
Using the INR at day 3 of a stable dose, we can extrapolate an estimation of what the full effect of warfarin will look like in a couple of days and compensate for that by adjusting the dose if necessary.
Warfarin is considered well managed if your patient is within range 65-70% of the time.
Warfarin Patient Education
Patients on warfarin need full and complete education about what this drug is, why they are taking it, what the tests are…everything. All this information should be provided face to face but also in simple written format.
This is alot of complex information and it is unreasonable to expect a patient to understand it all in one conversation. However, there are some key monitoring points, summarized below, that all patients should commit to memory. Knowing these could prevent poor outcomes.
What every patient should know:
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The information on this website is intended to be used solely for educational and informational purposes. While the content may be about specific medical and health care issues, it is not a substitute for or replacement of personalized medical advice and is not intended to be used as the sole basis for making individualized medical or health-related decisions.
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