Welcome to NP Certification Q&A presented by Fitzgerald Health Education Associates. This podcast is for NP students studying to pass their NP certification exam. Getting to the correct test answers means breaking down the exam questions themselves. Leading NP expert Dr. Margaret Fitzgerald shares her knowledge and experience to help you dissect the anatomy of a test question so you can better understand how to arrive at the correct test answer. So, if you're ready, let's jump right in.
A 68-year-old with atrial fibrillation is taking warfarin as part of therapy for the prevention of thromboembolic event. His goal INR is 2-3, which is checked monthly, and has been within an acceptable range for the past 6 months. Today he presents with an INR of 3.8. He denies bleeding events and reports, “I am taking the medicine just like I was told.” The NP considers that:
As we’ve done with other questions, where do we start? First, let's determine what kind of a question this is. Given that the patient has been diagnosed with atrial fibrillation, placed on warfarin to prevent a thromboembolic event, and now has a follow-up lab that's out-of-range or abnormal, this is an evaluation question.
As we do with all of these Q&As, let's take a look at some background information.
Since the advent of direct oral anticoagulants, also called the DOACs, the use of warfarin has decreased significantly. DOACs are considered first-line therapy for a number of clinical scenarios to avoid or treat thromboembolic disease. Indeed I would safely say that the vast majority of people with atrial fib would be now placed on a DOAC and not warfarin. However, DOAC use should be avoided in patients with antiphospholipid antibody syndrome, due to diminished therapeutic effect, and warfarin remains the drug of choice in select other thrombophilias. Another group where warfarin is preferred over a DOAC are patients at both ends or if you will more extremes of body weight, less than 50 kg, in other words, less than 110 lbs, or greater than 120 kg, or greater than 265 lbs, or BMI 35 kg/m2 or greater due to changes in the drug’s pharmacokinetics of the DOACs.
How does warfarin work? It’s an anticoagulant that acts against coagulation factors II, VII, IX, and X as a result of vitamin K antagonism; therefore, it is classified as a VKA or vitamin K antagonist. Warfarin is highly protein-bound, it’s about one of the most highly protein-bound drugs prescribed at a 99% protein binding. It is bound primarily to albumin. It also has a really narrow therapeutic range, and it is referred to as an NTI or narrow therapeutic index medication. And with narrow therapeutic index meds, those NTI meds, the way I always think of it is, a little bit less than what the patient needs and the patients not on enough, a little bit more than what the patient needs and they’re in toxicity range. I call warfarin a “fussy drug”, where significant patient education and appropriate provider monitoring is needed. And it comes with many drug-drug and drug-food interactions. When stable, INR is usually checked monthly. When there has been a change in patient status, such as initiation of an antimicrobial that will invariably cause an INR increase, INR monitoring needs to increase as well.
Why is it that all antimicrobials, some worse than others, impact INR? Even the most benign antimicrobials, something like an amoxicillin that has 0.0 drug-drug interactions will cause a bump up in the INR. All antimicrobials reduce gut flora, and that’s the source of the body’s endogenous vitamin K. When there’s less Vitamin K being produced because the gut flora is down, the formerly stable warfarin dose causes a bump up in INR. The same advice applies to the unavoidable addition of a medication that will interact with warfarin via cytochrome P450. That said, don’t ever feel as if a situation with an interacting med no matter what the two drugs are, don’t ever feel as if your back is solely against the wall and there’s nothing you can do to avoid this. PharmD consultation is very helpful and usually what you can do in consultation with the pharmacist is come to an agreement on a med that will either not interact with warfarin or have minimal impact on warfarin biotransformation and elimination.
Let’s take a look at the question and the options, breaking each down.
A 68-year-old with atrial fibrillation is taking warfarin as part of therapy for the prevention of thromboembolic event. His goal INR is 2-3, which is checked monthly and has been within an acceptable range for the past 6 months. Today he presents with an INR of 3.8. He denies bleeding events and reports, “I am taking the medicine just like I was told.” The NP considers that:
A. The INR should be repeated today.
That answer is incorrect. Seldom is repeating a lab test the right answer on the NP boards, as the laboratory studies currently available are typically highly reliable. When teaching a concept like this in an in-person board review, I'll often will hear from people who say, “But wait a minute, in the hospital we see labs repeated all the time!” Well, yes, that’s not just because the labs are unreliable, but more likely because the patient is unstable. The scenario here is presented that this man has been on the medicine for a number of months with stable INR, and now has had a minor bump up in his INR. This is not an emergency situation, I’m not doubting the veracity of the lab results.
A single dose of injectable vitamin K should be ordered.This is also incorrect. Given that warfarin is a vitamin K antagonist, this intervention is used on occasion when the INR is more elevated like > 4, and there is bleeding event or significant risk of a bleeding event. In this scenario, we are told his INR is up a bit, and that he's not bleeding. And you might say to yourself, yeah, but, I want more information about whether he is bleeding or not. You know, on the boards what you have to is assume you’ve been given enough information to answer the question and move on from there.
Option C. His health history should be reviewed carefully, with a focus on interacting medications and/or foods.
This is the best answer. The most common reason for an unexpected INR elevation is the use of an interacting medication, such as an antimicrobial or select CYP450 inhibitors or interacting foods, such as cruciferous vegetables that were ingested in large amounts. Of course, part of the intervention for this patient would include removing the problematic item from the patient’s med list, if possible, or removing the problematic food from their diet. The next step after that would be making the clinical decision if you encounter an interacting med, an interacting food about whether you feel the need to lower the warfarin dose over the next week or rather simply ride it out and see if removing the interacting substance is enough so that the warfarin dose is sufficient and his INR normalizes.
Option D obviously isn’t correct because it’s talking about his weekly warfarin dose should be increased by 15%. His INR is unacceptably elevated. If no interacting med was found in his med reconciliation, and no sudden onset ingestion of a lot of interacting foods or vegetables then reducing his total weekly warfarin dose by about 15% would be the next step in his treatment, with a follow-up INR in about 1 week. Skipping a single daily warfarin dose is usually only done with a markedly elevated INR. And the reason for that is that is skipping a day of warfarin really alters warfarin’s pharmacokinetics and makes the stabilization of the INR that much more challenging.
Key takeaway: Since the advent of the DOACs, warfarin use has decreased tremendously. However, it is critical for the nurse practitioner to know how to manage this important medication.
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