Do You Know What DOACs Do?

Andrea Perreault BSN RN

Considering that Coumadin (Warfarin) was first used on humans in 1954, it is likely that most of us have encountered it many times during our careers. I would hazard that all of us memorized INR ranges in nursing school. Maybe you are like me, and appreciated the clear-cut rules that guided decisions about giving or withholding Warfarin – especially in those early years when it seemed that so much of my crystal-clear nursing school training had given way to a sea of grey areas and need of a "nursing judgment" I had yet to develop. But over the past decade there has emerged a new class of anticoagulants, called DOACs (Direct Oral Anticoagulants), that seem to flaunt rules in general. As an OR nurse, I will discover that my patient is on such a medication and advise the surgeon of the last time it was taken, but I have not always been able to predict what happens next. Sometimes we go right on ahead with surgery, even if the medication has not been held. What's a nurse to do in the face of such willy-nilly handling of anticoagulants? I realized it was finally time to learn more.

A Very Basic Review of the Very Complex Process of Clot Formation

The mechanism through which clots are formed in our bodies inspires both wonder and confusion. There's so much going on! But a basic understanding really helps, so let's compare the clotting process to an average hospital unit.

WHO'S WALKING THE HALLS? These cells are circulating in the blood at all times

Platelets are the unit staff - nurses, patient care techs and respiratory therapists of the body.

Platelets – these cells congregate at the site of an injury, where they form the initial framework for the clot, and eventually, through cellular changes, recruit reinforcements.

Vitamin K is dietary. Mostly housed in certain parts of the hospital (like the cafeteria and various offices, aka liver, pancreas and brain) but providing services when needed.

Vitamin K – required in order for our bodies to produce several of the coagulation factors in the clotting cascade, including factors II (aka prothrombin), VII, IX, and X.

Prothrombin and Fibrinogen are the crash cart and defibrillator. Just standing by but super important.

Prothrombin (aka Clotting Factor II) – a protein made in the liver, and the direct precursor to thrombin. As we just learned, it needs Vitamin K in order to exist.

Fibrinogen – another very important protein made by the liver

SUDDENLY, THERE'S A PATIENT EMERGENCY!

The unit staff (Platelets) hurry to the patient's room (and, let's face it, a bunch of extra staff clump up in the hallway). Somebody hits the code button, and within seconds there's action in all directions. Nursing supervisor, pharmacist, respiratory therapist, physician and more and are all galvanized and interacting with one another to achieve a common goal. This complex interaction is the clotting cascade.

Clotting Cascade – The dizzying series of enzymatic reactions we all learned in nursing school, in which various "clotting factors" with names like Factor VII and Factor Xa act upon one another in a complicated but organized way.

SOMEBODY GRABS THE CRASH CART

Now Prothrombin and Fibrinogen aren't sitting in the hallway anymore, they're in the patient room. And that beautiful clotting cascade can turn the Prothrombin into Thrombin.

Thrombin – this enzyme is the second to last product of the clotting cascade.

Next thing you know Thrombin has turned Fibrinogen into Fibrin.

Fibrin – an elastic, stringy protein that winds around the platelet framework, adding support and strength to the clot.

Aha! Now that we have Fibrin our clump of staff has been woven together and strengthened. Now instead of a gaggle of people we have an organized, reinforced unit (clot) and our patient is saved. Hooray!

So now that we remember a little more about the clotting process, let's look at how the various medications work to prevent clot formation. And more importantly, let's see what that means for us and our patients.

Anticoagulants

Anticoagulants slow down the body's ability to form clots by delaying the formation of fibrin, that stringy, elastic protein which fortifies the clot.

Most common uses:

Patients with Nonvalvular afib (atrial fibrillation that is not related to a heart valve problem)
VTE
Treatment or prevention of PE

Warfarin – Old Faithful

How it works: Warfarin is a Vitamin K antagonist, which means it inhibits the synthesis of the 4 clotting factors that require Vitamin K. (Reminder – one of those factors is Prothrombin. The other are VII, IX and X).

Pros:

With decades of use under its belt, Warfarin is well understood and more is known about the effects of long-term use
Warfarin is less expensive than the newer anticoagulants
Warfarin may be less likely to cause GI bleeding
The effects can be reversed quickly when a patient needs surgery or has an acute bleeding episode. Warfarin can be reversed by administering oral or IV Vitamin K, or, in emergency situations, Prothrombin complex concentrate (PCC), fresh frozen plasma, or activated Factor VII treatment
For some people, the newer anticoagulants are contraindicated. We'll cover that in a minute.

Cons:

Blood tests are required in order to maintain a therapeutic level, which can be costly and inconvenient for patients, and may affect compliance
Dosages may need to be adjusted frequently, which can be confusing for patients
The effects of Warfarin can be affected by diet, alcohol intake, and other medications, which makes maintaining a consistent therapeutic level difficult. In one study, patients were found to be outside of the therapeutic range almost 50% of the time.
The biggest risk factor for Warfarin is bleeding. This can be serious or fatal, including intracranial hemorrhage.

Direct Oral Anticoagulants (DOACs) – Newer and exciting

DOACs received FDA approval in 2010, the same year the first iPad was released.

First, which drugs are they?

Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Edoxaban (Savaysa)
Dabigatran (Pradaxa)

How they work:

There are 2 main classes of DOACs which work in slightly different ways. However, both types work directly on one of the clotting factors. (Unlike Warfarin, which affects clotting factors indirectly by affecting Vitamin K)

Oral direct Factor Xa inhibitors inhibit the Clotting Factor Xa (Hint - notice the "XA-ban" in all of their generic names!)
- Rivaroxaban (Xarelto)
- Apixaban (Eliquis)
- Edoxaban (Savaysa)
There is one direct thrombin inhibitor, which binds to thrombin and prevents it from converting fibrinogen into fibrin.
- Dabigatran (Pradaxa)

Pros:

They have been shown to cause significantly less fatal and life threatening bleeding than Warfarin
They don't require regular blood tests
Most patients remain on the same dose all the time, which simplifies the patient's med regimen
They have fewer interactions with diet and other medications
They have a rapid onset of action and short half life, so they take effect more quickly, and wear off more quickly once discontinued

They sound great, right? But there are some Cons:

There are some clinical situations where patients on DOACs may have more clotting than patients taking Warfarin, such as those with mechanical heart valves and certain types of mitral valve stenosis
There are other clinical settings where there is uncertainty whether DOAC therapy should replace existing standard treatment regimens. For example, patients on DOACs for atrial fibrillation (AF) who now need percutaneous coronary intervention (PCI), patients with stable atherosclerotic cardiovascular disease (ASCVD), and patients with cancer‐associated thromboembolism.
Because they are metabolized in the kidneys and liver, impaired renal or hepatic function can prolong the effect of the medication
There is no established blood test to evaluate the therapeutic level or effect of DOACs
DOACs are more expensive than Warfarin, although the argument can be made that they reduce overall cost in other ways, for example by eliminating the need for routine blood tests
While reversal agents now exist (Praxbind for reversal of Pradaxa, and Andexxa for the Xa inhibitors), more research is needed to determine best practice for all clinical situations

What about elective surgery?

Since there is no DOAC version of the INR, guidelines for stopping and resuming DOACs are based on the procedure being performed and the specific medication the patient is taking. These guidelines are still being researched, and your facility may have its own clinical practice guidelines or recommendations. Generally speaking, however, elective procedures have been grouped according to risk of bleeding, with recommendations adjusted accordingly.

Minor bleeding-risk procedures: continue medication, or stop 12-24 hours before and resume 6 hours after. Examples of procedures in this category: cataract surgery, dental extraction.
Low bleeding-risk procedures: stop 24-96 hours before, and resume 24 hours after. Example: endoscopy with biopsy.
High bleeding-risk procedures: stop 48-96 hours before, and resume 48-72 hours after. Examples: major surgery, spinal puncture.

What about Aspirin and Plavix? A Word about Antiplatelet Agents

Antiplatelet agents also affect blood clotting, but do not fall into the Anticoagulant class. These medications prevent platelets from clumping together, which eliminates the building blocks for the clot. To return to our Hospital Unit analogy, instead of staff gathering in the hallway and patient room during an emergency, everyone would continue walking down the hallways, going about their business.

Most common uses:

Recent strokes
Acute and recent MIs
Acute Coronary Syndrome (ACS)
Peripheral vascular disease
After percutaneous coronary intervention (PCI) with stent placement

Aspirin and Plavix (Clopidogrel) - Aspirin and Plavix are two common antiplatelet agents. They have slightly different mechanisms of actions so may be used individually or together to prevent clots. They may also be combined with an anticoagulant. (Example: a patient who takes Xarelto for afib is placed on daily aspirin therapy following a stent placement)

The Bottom Line for Nurses

What I learned in my research is that there really aren't black and white rules when it comes to the management of patients on anticoagulant and antiplatelet therapy. Providers must weigh the risk of an unwanted clot against the risk of bleeding in each unique situation. And of course, they must consider the whole clinical picture for each patient, including comorbidities that increase the patient's risk for either clots or bleeding.

As nurses, we can do several things to advocate for our patients:

Be familiar with the basics of the medications involved so we can evaluate when our patients are at risk for a potentially dangerous situation. Hopefully this article has helped, but don't be afraid to consult online resources to refresh your memory in the heat of the moment.
Be aware of our patient's histories. Some things to look out for are:
- recent clot-related incidents, such as TIA/stroke, DVT or PE.
- recent cardiac history, including MI, Afib, valve disease, or stent placement
- recent bleeding episodes
Be familiar with any protocols or guidelines your facility uses
Don't hesitate to relay any concerns to your patient's physician
Provide patient teaching when needed

Over the next decade more will be learned about how DOACs affect patients in various clinical situations. As nurses we will be active participants in the evolution of this knowledge. Although I was grateful for the simplicity of the INR as a new grad, I now embrace the grey areas, because that's where the learning happens.

References/Resources

Warfarin: almost 60 years old and still causing problems

Direct Oral Anticoagulant Use: A Practical Guide to Common Clinical Challenges | Journal of the American Heart Association

How Blood Clots - Blood Disorders - Merck Manuals Consumer Version

Role of emerging vitamin K‑dependent proteins: Growth arrest‑specific protein 6, Gla‑rich protein and periostin (Review)

Vitamin K - Health Professional Fact Sheet

How it all starts: Initiation of the clotting cascade

Fibrinogen | definition of fibrinogen by Medical dictionary

Thrombin | definition of thrombin by Medical dictionary

Fibrin | definition of fibrin by Medical dictionary

Warfarin - FDA prescribing information, side effects and uses

Warfarin Isn't Going Away