Periprocedural Coumadin Management

We have recently been following KD, a 58-year-old male who was diagnosed with a first unprovoked deep vein thrombosis (DVT). After completing 3 months of treatment with warfarin, KD elected to continue warfarin therapy indefinitely in order to reduce his risk for a future DVT or pulmonary embolism (PE). 

KD has had consistently therapeutic international normalized ratios (INRs) and has not experienced any problems with his warfarin therapy. However, in 2 weeks, he is scheduled to undergo a screening colonoscopy that he had originally avoided when offered at age 50. 

The gastroenterologist performing the procedure has instructed KD to have his primary care clinician manage the periprocedural anticoagulation, expecting that warfarin treatment would be paused 5 days before the procedure. KD scheduled an appointment on July 21 with his primary care clinician to plan anticoagulation strategy for the intended colonoscopy of July 28. 

Three primary questions need to be addressed:

1. What is the risks if anticoagulation is not discontinued?

2. What are the benefits of discontinuing anticoagulation?

3. If anticoagulation is discontinued, which patients should receive bridge therapy? (For more on bridge therapy, see “Anticoagulation Treatment for DVT” Consultant, June 2014, page 494-496.)

Risks if Anticoagulation
Is Not Discontinued

The answer may surprise you: Continuation of anticoagulation with warfarin has not been shown to increase mortality in the setting of an operative procedure. One might intuitively think that surgical procedures during fully active anticoagulation would be associated with more surgical deaths, but the literature does not confirm it.

That being said, if continued anticoagulation does not increase mortality, why would we discontinue it? It is primarily because surgery becomes more complicated if performed in an anticoagulated patient. There is consistent data that anticoagulated patients (whether through heparinoids, warfarin, and/or other antiplatetelet agents) who undergo surgery incur more bleeding. Further, other consequences may include lower hematocrits, an increasing need for transfusions, longer length of hospitalization, and prolonged duration of surgery due to the anticipatable greater efforts required to ensure and maintain hemostasis, as well as the direct obstacle of having more blood in the surgical field during the procedure. 

Any surgeon would prefer to have the best possible coagulation status to avoid these consequences. On the other hand, we have substantial experience with patients who required urgent surgery without an opportunity of anticoagulant discontinuation; therefore, we conclude that anticoagulated patients do not suffer increased surgical mortality. This observation give us the rationale for stratifying each patient’s risk for thrombosis before deciding how best to manage perioperative anticoagulation.

Benefits for Discontinuing Anticoagulation

As mentioned previously, anticoagulation discontinuation provides a more positive surgical and postsurgical environment for bleeding risk and the consequences of bleeding.

Deciding on Bridge Therapy

This is difficult to answer because bridging is expensive, inconvenient, a little bit complicated, and is associated with its own toxicities. In any case, the decision about whether to provide bridging is based upon each patient’s risk for thrombosis off warfarin. 

• Patients who are considered low risk can simply discontinue their warfarin and undergo the surgical procedure without any anticoagulant on board, usually restarting their warfarin within 24 hours of completion of surgery without heparinoid bridging. 

• Patients who are high risk for thrombosis off of warfarin are provided bridging therapy, and also reinitiate warfarin within 24 hours of completed surgery. (Note: All assumptions about warfarin reinitation are predicated based on the patient being stable with no signs of problematic bleeding).

•  Patients at moderate risk of thrombosis require individualization of consideration. If the expense, tolerability issues, or personal preferences of bridging therapy appear more burdensome than the risk reduction provided by inclusion of bridging, it may be omitted. Alternatively, for a patient at moderate risk of thrombosis off warfarin who values highly the ability to reduce risk maximally and is willing to shoulder the burdens of bridging therapy, it is reasonable to utilize it.

Research

There is little evidence from randomized trials to guide the clinician in this commonly encountered clinical scenario; most recommendations are formulated from expert opinion which attempts to stratify risk for thromboembolism off warfarin as low (<5%), moderate (5% to 10%), or high (>10%).¹

Perhaps the most robust data to establish off-warfarin thrombotic risk is from placebo arms in randomized controlled trials of anticoagulant treatment for atrial fibrillation, thanks to the availability of a validated risk-scoring system (CHAD2) that quantifies the risk for stroke or venous thromboembolism (VTE). (For more on CHADS, see “Warfarin and Atrial Fibrillation,” Consultant, March 2014, page 215-216.)

• High-risk patients (CHADS2 score of 5 or 6) should be routinely considered for bridging therapy, given their high risk for thrombosis off warfarin when compared to the excellent risk reduction attainable with subcutaneous heparinoids and very low risk of bleeding associated with heparinoid use. 

• Low risk groups (CHADS2 score of 0 to 2) can likely safely temporarily discontinue warfarin due to an estimated yearly risk for stroke of <5%. 

• Those with a moderate risk (CHADS2 score of 3 to 4) present a more difficult decision that is likely to be case specific; although the risk for VTE may be relatively easy to calculate in moderate-risk patients, the risks for bleeding of the individual patient are likely to vary significantly. 

It is important to remind patients that there is not a “no-risk” path: All choices are a best estimate of competing risks, so that even a patient considered low risk for VTE or stroke is not no-risk; hence, the global strategy of omitting bridging for persons designated low risk will still result in a very small number of persons incurring thrombosis during the interval when bridging therapy was omitted. 

Unfortunately, for patients with an isolated history of DVT or PE (like our patient KD) there is minimal evidence to guide the clinician, although expert opinion has been published.¹ 

• Those with recent VTE (in the last 3 months), documented thrombophilia (eg, antiphospholipid antibody syndrome or factor V Leiden disorder), or mechanical heart valve replacement are considered to be high risk and are recommended to receive heparinoid treatment. 

• In the absence of history of recurrent VTE, and as long as the index VTE was at least 12 months prior, expert opinion considers the patient to be low risk, thus below the threshold for heparinoid bridging. 

• Patients at moderate risk with a history of recurrent VTE or VTE in the last 3 to 12 months pose a more difficult clinical scenario due to the difficulties in accurately determining the risks for VTE compared to the risk for bleeding. As we noted in “Anticoagulation Treatment for DVT” (Consultant, June 2014, page 494-496), the annual risk for recurrent VTE after an isolated event ranges from 5.6% to 8.8%; a risk of 8% is equivalent to a CHADS2 score of 4 in terms of risk for VTE in atrial fibrillation patients. 

Other Considerations

Patient-centered factors are also likely to play a role in determining whether or not heparinoid therapy will be implemented. Costs of heparinoid therapy can be substantial as the total duration of treatment will likely be 10 to 14 days. The patient will have to be covered for at least 5 days prior to the procedure when the warfarin is discontinued and an additional 5 to 7 days following resumption of warfarin therapy once the procedure is complete (ie, it will typically require at least 5 days after reinstitution of warfarin to be confident that the warfarin has attained its full therapeutic effect, allowing heparinoid discontinuation). 

In our experience, resuming warfarin following a planned discontinuation often does not elicit a therapeutic INR in the expected 5 to 7 days as would be expected in a patient who started warfarin for the first time. Although uncommon, as long as 21 days of bridge therapy may be needed before the heparinoid can be safely discontinued, and the patient maintained solely on warfarin again. This, of course, can lead to a substantial financial burden for certain patients. As noted previously, patients with insurance often have a single copay and therefore ordering 14 or 21 days of treatment may be preferred to shorter durations in order to limit costs. 

For patients at moderate thrombotic risk, a number of factors should be taken into account to help determine whether bridging treatment is right for that particular patient. 

• Not all patients may have the same abilities to administer the heparinoid reliably and correctly. 

• Factors such as health literacy, dexterity, and vision, to name a few, will have to be considered when determining the safety of heparinoid therapy in addition to the bleeding risks. 

• Negative prior experiences with heparinoid (most commonly local hematomas, pain of injection, and persistent pain at injection sites) should be identified, since a patient who is nonadherent to the dosing regimen will not gain appropriate risk reduction. 

Note: The presence of such factors may tilt the risk-to-benefit balance of heparinoid therapy such that the risks outweigh the benefits. 

Finally, intraoperative strategies to limit bleeding risk may also be able to be used as opposed to discontinuing anticoagulation therapy. A recent clinical trial reported that use of a “cold forceps technique” for polypectomy during colonoscopy reduced bleeding to a level comparable to controls (ie, patients not receiving anticoagulants). However, we are unsure of the widespread availability or application of this technique.

What's the "Take Home"?

1. There is a lack of evidence to show increased mortality with continued anticoagulation during surgical procedures, although bleeding complications are increased compared to individuals that discontinued anticoagulation.

2. Risk assessment for bleeding and thrombosis is an imperfect science. Expert opinion attempts to stratify risk categories of <5%, 5% to 10%, and >10% based on past medical history.

3. Those with an estimated risk for VTE of ≥10% should receive bridge therapy with a heparinoid, while those with a risk <5% should likely not receive
bridge therapy.

4. Those with a risk of 5% to 10% should be evaluated on a case-by-case basis to determine the risk-to-benefit profile for bridge therapy. Patient-related factors are likely to be a key component in determining the appropriateness of bridge therapy.  

Next month:Once we have decided that bridging therapy is merited, how should we go about it? ■

Eric A. Dietrich, PharmD, BCPS, graduated from UF College of Pharmacy in 2011 and completed a 2-year fellowship in family medicine where he was in charge of a coumadin clinic. He now works for the UF Colleges of Pharmacy and Medicine. 

Louis Kuritzky, MD, is a family physician affiliated with the University of Florida Family Medicine Residency Program, where he commonly co-manages warfarin cases with his colleagues.

References:

1.Douketis JD, Berger PB, Dunn AS, et al. The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133 (6 Suppl):299S-339S.