Anticoagulants in dermatology

By Allison Evans, Assistant Managing Editor, June 1, 2022

Writing a script for an anticoagulant is not something dermatologists typically do, although these medications play an important role in clinical and surgical practice. The anticoagulant world has advanced significantly in the past few decades, with the transition from primarily vitamin K antagonists to the newer direct oral anticoagulants (DOACs), and additional, and potentially more effective antiplatelet agents are now available. Dermatologists discuss approaches to managing patients on these medications during the perioperative period as well as how DOACs may play a future role in managing some dermatologic conditions.

In general, dermatologists do not personally manage antithrombotic medications for non-surgical reasons, said Spyros Michael Siscos, MD, chief dermatology resident at the University of Kansas Medical Center. “However, most dermatologists perform dermatologic procedures or surgeries on a daily basis, so dermatologists should possess an understanding of perioperative antithrombotic management, particularly with the newer DOACs.”

Direct oral anticoagulants

The proportion of patients taking direct oral anticoagulants, including dabigatran, rivaroxaban, and apixaban, is growing every single year as studies have shown their efficacy across a range of conditions, said Arash Mostaghimi, MD, MPH, FAAD, assistant professor of dermatology, director of the Dermatology Inpatient Service, and co-director of the Complex Medical Dermatology Fellowship at Brigham and Women’s Hospital.

The DOACs offer many therapeutic advantages over warfarin and other vitamin K antagonists, including a more rapid and predictable anticoagulant response, limited need for routine laboratory monitoring, and fewer drug-food and drug-drug interactions, studies suggest.

Dermatologists must be aware of their use, Dr. Mostaghimi said. If not managed correctly in the perioperative setting, patients may develop complications ranging from increased intraoperative bleeding to post-operative hematoma or skin graft compromise. The newer anticoagulants may also adversely interact with common dermatologic drugs, placing patients at increased risk for bleeding or thrombosis.

“Before the direct oral anticoagulants started taking hold, warfarin and heparin were most widely used. Heparin requires intravenous infusion or subcutaneous injections, and warfarin affects multiple factors of the clotting cascade. In contrast, the newer anticoagulants are taken orally and specifically inhibit one factor — often factor Xa,” Dr. Mostaghimi said. “By blocking that factor, it provides a very reliable anticoagulant effect that works quickly and does not require monitoring.”

Unlike warfarin, which can be reversed with fresh frozen plasma and vitamin K, DOACs require specific, sometimes difficult-to-obtain reversal agents that can be used in the event of hemorrhage or overdose, Dr. Mostaghimi said. “The shorter half-life of these drugs, however, often means that simply discontinuing the medication is enough to deal with mild complications.”

However, if bleeding is severe, oral-activated charcoal can be used to remove unabsorbed drug from the gastrointestinal tract if the drug was taken within the past two hours. Dialysis may be used to remove dabigatran, although this is not an option for reversal of rivaroxaban or apixaban, which are largely protein bound (https://doi.org/10.1016/j.jaad.2014.11.013). Direct oral anticoagulant reversal agents are available but have a risk of thrombosis and can only be given intravenously.

International normalized ratio (INR) and partial thromboplastic time have traditionally been used to gauge a patient’s level of anticoagulation when on warfarin. However, data from the newer agents suggest that they have variable and inconsistent effects on these tests, making them unreliable, Dr. Mostaghimi said.

Guidelines

“Historically, guidelines in the dermatologic literature have recommended continuing warfarin and antiplatelet medications such as aspirin and clopidogrel during the perioperative period,” Dr. Siscos explained. “These guidelines are due, in part, to the risk of an ischemic stroke or deep vein thrombosis that are associated with discontinuing antithrombotic medications.” The risk of a vascular event was thought to outweigh the possibility of significant perioperative bleeding.

These recommendations have been extrapolated to also include the newer DOACs. However, DOACs have unique properties that make their perioperative discontinuation safer compared to other antithrombotic medications, he added.

In 2017, the American College of Cardiology (ACC) issued guidelines stating that DOACs may be discontinued ≥24 hours before — and resumed the day after — procedures with a low bleeding risk. “Additionally, the ACC recommended longer periods of DOAC interruption for procedures with a higher bleeding risk such as reconstructive plastic surgery. Multiple procedural subspecialties including ophthalmology and gastroenterology have started to include timeframes for periprocedural DOAC discontinuation in their working guidelines,” Dr. Siscos said.

Dermatologic surgery best practices

The vast majority of dermatologists’ interaction with anticoagulants is when they perform a biopsy or an excision, or some sort of dermatologic procedure, Dr. Mostaghimi said. About 25-38% of patients who undergo cutaneous surgery are taking an antithrombotic agent that puts them at a slightly elevated risk for bleeding (https://doi.org/10.1016/j.jaad.2017.05.038).

“We do not have a lot of data on the direct oral anticoagulants and surgical outcomes in dermatology,” Dr. Mostaghimi noted. “But the general data from any anticoagulation is that the rate of bleeding-related complications is increased marginally.” While continuing anticoagulation appears to have limited risk, the negative consequences of discontinuing anticoagulation therapy may be higher, including serious thromboembolic events.

In most situations, dermatologists should keep patients on their anticoagulant medications, affirmed Hugh Gloster, MD, FAAD, a Mohs surgeon practicing in Florida. “The reason is that although some of them definitely do increase the risk of bleeding, the thought is that the risk of bleeding, at least for skin surgery, is usually pretty easy to manage by the surgeon. Worst case scenario: a patient returns, and you have to open it up and cauterize it, which is not as severe as the patient having a serious clot, stroke, or heart attack if you take them off of the medication.”

Patients taking anticoagulants or antiplatelet therapies need to be aware of the increased risk of bleeding, Dr. Gloster said. “For example, studies have shown that a patient taking clopidogrel has an eight-fold increased risk of bleeding versus someone on aspirin alone, and a 28-times risk of bleeding versus someone not taking anything.”

“While we usually continue patients on their blood thinners, we take certain precautions,” Dr. Gloster said. “I ensure thorough hemostasis is obtained with electrocautery devices, I’ll use topical hemostatic agents, put extra firm pressure dressings on, and really stress the post-operative instructions like icing and reduced activity. We are extra vigilant about those precautions.”

Interruption of anticoagulants

“There are a few extenuating circumstances where we might consider reaching out to a cardiologist and asking if the patient can come off the medication. If it was a really extensive surgery with a complicated repair, that might be a situation where we’d consider discontinuing the medication before the surgery,” Dr. Gloster said.

“If there is a particular reason or concern about keeping the patient on anticoagulation, it’s best to consult with the prescribing physician to determine whether the medication can be stopped safely, and if so, for how long.” Dr. Mostaghimi said.

With more complicated procedures, it’s important to remember that these newer anticoagulants start working and stop working very quickly, Dr. Mostaghimi said. “Even missing a single dose can reverse the medication’s effects and increase the risk of clot and other complications. On the other hand, our patients need to understand that being on an anticoagulant agent during surgery is an added risk. The best approach is for dermatologists to be transparent and engage in shared decision making with patients in those situations.”

However, if patients are on non-essential blood thinners, like daily aspirin for primary prevention, I will instruct patients to discontinue that, Dr. Gloster noted. “I also tell patients to stop taking certain supplements as well, like vitamin E, fish oil, ginkgo biloba, ginger, and garlic. While they are often not potent blood thinners, I still prefer to take patients off of them before a procedure.”

Dr. Siscos and his colleagues published a study in JAAD looking at how interrupting DOAC therapy in patients with nonvalvular atrial fibrillation or a history of deep vein thrombosis affected rates of thrombotic complications.

“In our study, no patient sustained an ischemic stroke or deep vein thrombosis and only two patients sustained minor bleeding complications. The majority of dermatologic surgeries in our study involved large reconstructive facial procedures which may limit the generalizability of bleeding complications in dermatologic surgeries, which may be lower for general dermatologic procedures. For example, from a bleeding complication standpoint, a patient undergoing reconstructive surgery that involves a large flap on the cheek may benefit more from DOAC discontinuation than a patient undergoing a small procedure on his or her back.”

“If a patient is instructed to discontinue a DOAC during the perioperative period, then they should be thoroughly counseled on the signs and symptoms of thrombotic events,” Dr. Siscos said. Ultimately, we need more studies to help establish best practice guidelines for DOAC management in dermatology, Dr. Siscos added.

“What we are missing are data that analyze the impact of these medications on procedures in dermatology,” Dr. Mostaghimi said. “It’d be nice to have a set of studies that specifically look at these new drugs or looking at these drugs in combination with antiplatelet agents. We don’t know the combined effect of these, but for now, being judicious, thoughtful about your approach, and transparent with the patient is the best path forward.”

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