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Mohs Micrographic Surgery Anticoagulants And Hemostatic Agents Impact
Introduction
Mohs micrographic surgery (MMS) is a specialized dermatological surgical technique frequently employed when treating non-melanoma skin cancers. MMS is considered a safe surgical procedure with a low overall risk of perioperative complications.[1] A minor amount of intraoperative bleeding is expected during MMS; such bleeding is easily controlled with a combination of electrocautery, gentle mechanical pressure, or topical hemostatic agents. However, rare occurrences of more severe perioperative bleeding may lead to hematoma formation, wound dehiscence, and potential loss of grafts or flaps.
Patients undergoing MMS during the concomitant use of antiplatelet or anticoagulant therapy are at increased risk of perioperative bleeding and subsequent complications.[1][2] Direct-acting oral agent (DOAC) anticoagulant therapy is increasing in frequency and may pose additional perioperative bleeding risks.[3]
A comprehensive understanding of the risks associated with antiplatelet and anticoagulant medications, partnered with diligent perioperative management and meticulous attention to intraoperative hemostasis, is necessary to reduce complications in patients undergoing MMS during concomitant anticoagulation therapy. This activity will review the current recommendations for the perioperative management of these patients, including the risks, benefits, and technical considerations.
Issues of Concern
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Issues of Concern
Patients undergoing MMS commonly have medical comorbidities with the potential to impact surgical outcomes. Of particular interest is the widespread utilization of antiplatelet and anticoagulant therapies that may increase the frequency of bleeding-related complications. An estimated 25% to 38% of patients undergoing dermatologic surgery are on at least one anticoagulant or antiplatelet agent during the perioperative period.[4] While the consensus is that anticoagulation therapies are safe to continue during the perioperative period, the MMS practitioner must be aware of their use and understand the associated surgical risks.[5]
Many studies have investigated the impact of commonly used antithrombotic agents on the risk of hemorrhagic complications in MMS.[6] The risks of perioperative bleeding-related complications vary with specific drug classes and combination therapies.
Antiplatelet Medications
Antiplatelet agents are a class of pharmaceuticals that inhibit or decrease platelet aggregation, thereby increasing bleeding time. Aspirin and clopidogrel are among the most common antiplatelet agents prescribed to patients commonly undergoing MMS.[3][7] Studies have consistently demonstrated that aspirin monotherapy does not increase the risk of postoperative bleeding and is not associated with a significant increase in hemorrhagic complications in patients undergoing cutaneous surgery, including MMS.[8][9] The impact of clopidogrel monotherapy on bleeding risks is less conclusive; studies indicate either no increased or a mildly increased risk of perioperative complications in dermatologic surgery compared to patients not taking antiplatelet and anticoagulant medications.[10][7][11][12][13]
However, when clopidogrel and aspirin are combined with other agents, there appears to be a synergistic effect on the risk of bleeding-associated complications. A study revealed that multidrug anticoagulation regimens containing clopidogrel conferred significantly increased risks of bleeding-related complications compared to patients on no anticoagulation or aspirin monotherapy.[11] The same analysis revealed significantly increased complications in patients on dual antiplatelet therapy with clopidogrel and aspirin compared to patients on aspirin monotherapy. Other studies corroborate this increased risk from multidrug anticoagulation regimens.[7][14]
Anticoagulant Medications
Oral anticoagulants that directly target the coagulation cascade rather than platelet formation are also of concern. Warfarin is a well-established vitamin K antagonist and remains a commonly prescribed anticoagulant in patients undergoing MMS.[3] A recent meta-analysis revealed that patients undergoing MMS or excisional treatment of skin cancers were 7 times more likely to have bleeding-related complications than patients not taking anticoagulant therapy.[15] A study by Nast et al revealed a significant increase in minor and moderate bleeding in patients taking warfarin compared to controls.[8] However, some studies indicate that warfarin monotherapy is not associated with an increased risk of surgical complications.[16]
While the data may be conflicting, there appears to be a slight increase in bleeding complications associated with warfarin in patients undergoing minor cutaneous surgery.[13][17] This risk increases further when warfarin is combined with antiplatelet agents such as clopidogrel.[7][11][18] While an international normalized ratio (INR) may be obtained before surgery to assess the degree of anticoagulation in a patient undergoing cutaneous surgery while on warfarin monotherapy, several studies have shown no clear difference in bleeding complications based on preoperative INR value.[13]
DOACs such asapixaban, rivaroxaban, and dabigatran are more effective in treating various cardiovascular conditions than traditional anticoagulants, and their use has increased accordingly.[3] Although the available data regarding hemorrhagic complications during concomitant use of these agents is limited, recent studies have demonstrated these agents may pose an even greater risk of hemorrhagic complications than previously studied agents. Anita et al showed a bleeding complication rate of 1.3% in patients on DOACs undergoing MMS compared to a rate of 0.7% for all other patients, although this difference was not significant.[19] A subsequent study revealed that hemorrhagic complications in patients taking DOACs were 7 times more likely compared to other anticoagulant classes.[18]
Clinical Significance
Despite the increased risk of perioperative bleeding-related complications in patients undergoing MMS during concomitant anticoagulation therapy, the current recommendation is for patients to continue these agents during the perioperative period.[5] Discontinuation of clinically indicated anticoagulant or antiplatelet therapy is not without risk, and even brief interruptions in therapy may lead to catastrophic thrombotic events, the risk of which generally outweighs the increase in hemorrhagic complications of dermatologic surgery.[20][21] Adverse effects related to antiplatelet or anticoagulant therapy are often minor and easily managed.[4][22] While there is a relative increase in the risk of hemorrhagic complications attributable to antiplatelet or anticoagulant therapy, the absolute increase of these complications appears minimal, even for multidrug therapeutic regimens.[7]
Given the current evidence, withholding antiplatelet and anticoagulant agents, including DOACS, before MMS is not routinely recommended.[18] Aspirin taken for analgesia instead of antiplatelet activity may be safely held in the perioperative period. Obtaining an INR for patients on warfarin is neither required nor common practice; if a preoperative INR indicates supratherapeutic treatment, consultation with the prescribing provider or postponing the MMS procedure is warranted.[23]
Other Issues
Mitigating the risks of hemorrhagic complications in the anticoagulated patient undergoing cutaneous surgery requires meticulous attention to intraoperative technique and hemostasis.[24] Optimal intraoperative hemostasis provides several surgical benefits, including improved visualization of the surgical field, enhanced technical precision, reduced procedure time, and risk reduction.[25][26] Achieving intraoperative hemostasis is especially important in the anticoagulated patient; several hemostatic modalities may be employed.[26] Electrosurgery is the most effective and commonly used method of achieving hemostasis in dermatologic surgery due to its ease of use, availability, and efficiency.[27] Hemostatic agents are also commonly utilized to achieve hemostasis in most dermatologic procedures and can be used as monotherapy or as part of a multimodal approach. Postoperative pressure dressings can be applied to assist with hemostasis as appropriate.[24][28]
While hemostatic agents can benefit hemostasis in anticoagulated patients, no single agent suits every clinical circumstance. Topical hemostatic agents used in cutaneous surgery include caustic, noncaustic, and physiologic agents, each with a different mechanism of action.
Caustic Agents
Applying topical caustic hemostatic agents induces hemostasis by inducing tissue necrosis and protein coagulation, leading to thrombus formation in the exposed cutaneous vessels.[29] Topical caustic hemostatic agents include ferric subsulfate, aluminum chloride, and zinc paste, commonly used in superficial wounds created by shave or punch biopsies. Aluminum chloride is the most frequently used agent in this class due to its low cost, widespread availability, and minimal adverse effect profile characterized by mild pain and tissue irritation.[29] Ferric subsulfate, compounded as Monsel solution, is equally effective but has fallen out of favor somewhat due to the risk of permanent dyspigmentation from dermal iron placement.[30] The use of zinc paste, primarily composed of zinc chloride, was described by Frederic F. Mohs in the chemical fixation of skin cancer. However, despite its anti-tumor properties, it is now infrequently used in the context of MMS.[29]
Noncaustic Agents
Noncaustic hemostatic agents include physical substances that promote clot formation by providing a meshwork for platelet aggregation and coagulation.[31] Commonly used agents in this class include products containing gelatin, cellulose, collagen, or hydrophilic polymers, which can be formulated in vehicles such as powders and foams that are easy to apply. Although these agents are typically meant to dissolve over time, foreign body reactions have been reported.[32] Topical hemostatic agents with collagen are often bovine-derived and can lead to hypersensitivity reactions.[33] Additionally, applying cellulose agents has been associated with granulomatous reactions, delayed wound healing, and swelling at the application site.[31]
Physiologic Hemostatic Agents
The physiologic class of hemostatic agents mimics or enhances stages of the coagulation cascade following tissue application and includes thrombin derivatives, platelet gels, and fibrin sealants.[29] While physiologic agents are potent and effective at achieving hemostasis, this medication class is expensive and less frequently employed in dermatologic surgeries. Topical fibrin sealant has been associated with a hypersensitivity reaction in some patients and may rarely cause neurotoxicity.[27] Topical thrombin has been associated with an increased risk of coagulopathy due to subsequent antibody formation to bovine-derived thrombin after exposure; this adverse effect is uncommon.[34]
Areas of Ongoing Research
Brimonidine, an α-2 adrenergic agonist, may have a role as a hemostatic agent due to its vasoconstrictive properties. A small controlled study revealed the application of topical brimonidine gel before MMS resulted in decreased bleeding and a reduced need for electrocautery.[25] However, a later study reported altered mental status in patients following the application of topical brimonidine and ultimately recommended further evaluation of its safety before its routine use in MMS.[35]
Enhancing Healthcare Team Outcomes
Interprofessional collaboration among healthcare team members is essential to managing a patient undergoing MMS. These patients often inquire if it is necessary to stop antiplatelet or anticoagulation therapy before surgery; some patients preemptively hold these medications without discussion with the healthcare team. Nurses and medical assistants are essential in preoperative patient assessment and screening patients for antiplatelet or anticoagulant regimens.
Adequately counseling patients regarding the safety of perioperative antithrombotic therapy provides reassurance and minimizes the thrombotic risks associated with temporary discontinuation of the medication regimen. While consultation with the prescribing practitioner is rarely necessary, any concerns regarding the perioperative management of antithrombotic medications should be discussed directly with the prescribing practitioner.
Hemorrhagic complications associated with antithrombotic therapy can be minimized with meticulous attention to hemostasis and the postoperative application of a hemostatic dressing. Patients should receive education regarding postoperative wound care and the warning signs of hemorrhagic complications, including hematoma formation.
References
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