Mayo Clin Proc, November 2003, Vol 78 Perioperative Anticoagulant Therapy 1393 patients such that life-threatening complications would be a major risk

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1 1392 Review Continuation of Medically Necessary Aspirin and Warfarin During Cutaneous Surgery CLARK C. OTLEY, MD Excisional cutaneous surgery is performed commonly in patients who take medically necessary aspirin or warfarin. Although controversy has existed regarding the appropriate perioperative management of anticoagulant therapy during cutaneous surgery, recent data suggest that the risk of severe hemorrhagic complications is not increased if these medications are continued. Brief perioperative discontinuation does not lower this already minimal hemorrhagic risk. Furthermore, life-threatening thromboembolic complications have been related temporally to perioperative discontinuation of both aspirin and warfarin. In light of the absence of benefit and the presence of risks associated with discontinuation of warfarin and aspirin perioperatively during excisional cutaneous surgery, continuation of these medications is recommended in most situations. In all cases, the individual patient s medical history and risk factors should be taken into account when making this clinical decision, and deviation from the guidelines should be considered if clinical imperatives warrant. Mayo Clin Proc. 2003;78: Optimal management of anticoagulant therapy before and after cutaneous surgery is debatable. Availability of new data relevant to various aspects of this common clinical management decision prompts reformulation of data-based guidelines. Because multiple specialties are involved in decisions about perioperative management of anticoagulant therapy, this new information merits wide dissemination. Several management options are available for perioperative management of anticoagulant therapy, each with advantages and disadvantages. Continuing anticoagulant therapy during surgery minimizes the risk of thrombotic complications but theoretically increases the risk of hemorrhage. Discontinuing anticoagulant therapy may expose patients to life-threatening thrombotic events, albeit for a brief period, while presumably reducing the risk of hemorrhagic complications. Perioperative conversion to anticoagulant therapy with heparin and discontinuation only for the immediate perioperative period may reduce the duration of unprotected thrombotic diathesis but necessitates costly hospitalization and inconvenience. Use of lowmolecular-weight heparin in cutaneous surgery has been explored insufficiently. Although warfarin and aspirin have different mechanisms of action and are indicated primarily in different conditions, considerations regarding their perioperative use are similar. The goals of this article are to (1) outline the relevant issues regarding the decision to continue or discontinue From the Division of Dermatologic Surgery, Mayo Clinic, Rochester, Minn. Address reprint requests and correspondence to Clark C. Otley, MD, Division of Dermatologic Surgery, Mayo Clinic, 200 First St SW, Rochester, MN anticoagulant therapy during cutaneous surgery, (2) review recently available data pertinent to the decision-making process, and (3) present reasonable data-based recommendations for the use of medically necessary aspirin and warfarin at the time of cutaneous surgery. CURRENT STANDARD OF PRACTICE Current standards for perioperative management of anticoagulant therapy during cutaneous surgery diverge from both previously published guidelines and recently available data. A recent survey of the practice standards of members of the American College of Mohs Micrographic Surgery and Cutaneous Oncology revealed that 80% of surgeons sometimes or always discontinue warfarin in the perioperative period. 1 Likewise, cutaneous surgeons discontinue aspirin in 26% of cases, even if it is medically necessary. 1 These findings are similar to those of a survey of American Intraocular Implant Society members, which noted that 75% and 53% of surgeons withheld warfarin and aspirin, respectively, in the perioperative period for intraocular lens implantation. 2 Many physicians practice without guidelines regarding this clinical decision, as evidenced by a study in which 67% of members of the Neuroanaesthesia Society in the United Kingdom and Eire reported having no personal or departmental policy for perioperative management of aspirin therapy in patients undergoing neurosurgical procedures. 3 The most recent recommendations for perioperative management of warfarin and aspirin in the dermatologic surgery literature were published in That article predates publication of current data needed to establish scientifically sound recommendations. With regard to aspirin, the authors assert that there is no group of high risk Mayo Clin Proc. 2003;78: Mayo Foundation for Medical Education and Research

2 Mayo Clin Proc, November 2003, Vol 78 Perioperative Anticoagulant Therapy 1393 patients such that life-threatening complications would be a major risk if aspirin were temporarily discontinued. This statement is unsubstantiated and contradicted by more recent data. On the basis of theoretical considerations, the authors recommended discontinuing aspirin therapy for 7 days preoperatively and resuming it 1 day postoperatively. In their guidelines for managing warfarin therapy, Goldsmith et al 4 conceptualized 2 groups of patients: those at high risk for thromboembolism and those at low risk. For patients at high risk for thromboembolic complications, discontinuation of warfarin with concurrent perioperative administration of heparin was recommended. For low-risk patients, discontinuation of warfarin 3 days before and resumption 1 day after surgery were advised. Based on the data available in 1993, these recommendations were reasonable. In light of currently available data, revision of these guidelines is warranted. RELEVANT CONSIDERATIONS The decision to continue or withhold warfarin or aspirin in the perioperative period should be based on the current medical literature. By weighing the risks associated with continuing vs discontinuing warfarin or aspirin, rational guidelines can be derived to enhance patient safety. When devising management guidelines, the data underlying the following questions must be considered. 1. What Is the Baseline Risk of Hemorrhagic Complications During Cutaneous Surgery in Patients Who Are Not Taking Warfarin or Aspirin? Cutaneous surgery is associated with a low risk of complications and rarely provokes life-threatening problems. Data on the incidence of hemorrhagic complications can be obtained from the control groups in 2 related studies. 5,6 The risk of postoperative oozing or hematoma formation in patients who are not taking warfarin or aspirin is approximately 1.4%, and no life-threatening complications have been documented. 2. What Is the Risk of Hemorrhagic Complications During Cutaneous Surgery in Patients Who Are Taking Warfarin or Aspirin? Six studies published since 1994 quantify the incidence of hemorrhagic complications during cutaneous surgery in patients who are taking warfarin or aspirin The results of these studies are summarized in Table 1. Briefly, data from 6 peer-reviewed studies suggest that the risk of hemorrhagic complications does not increase during cutaneous surgery in patients who take warfarin or aspirin. Furthermore, life-threatening or lethal hemorrhagic complications have not been reported in patients undergoing cutaneous surgery while taking warfarin or Table 1. Risk of Hemorrhagic Complications During Cutaneous Surgery in Patients Taking Warfarin, Aspirin, or NSAIDs* No. of Controlled Increased severe Drug and study patients study complications Aspirin and NSAIDs Otley et al Yes No Billingsley & Maloney 6 97 Yes No Lawrence et al Yes No Bartlett 9 52 Yes No Warfarin Otley et al 5 26 Yes No Billingsley & Maloney 6 12 Yes No Lam et al 7 13 Yes No Alcalay 8 16 Yes No *NSAIDs = nonsteroidal anti-inflammatory drugs. aspirin. This primary observation renders most of the other questions moot: if continuation of anticoagulants carries no major risk for complications, there is no compelling reason to disrupt medically necessary therapy. 3. Does Temporary Discontinuation of Warfarin or Aspirin Reduce the Risk of Hemorrhagic Complications During Cutaneous Surgery? Multiple studies have shown no increased risk of hemorrhagic complications in patients undergoing cutaneous surgery while taking warfarin or aspirin compared with controls. Thus, the possibility that brief perioperative discontinuation of these medications may effectively reduce complications is a moot point. In the only study that tested this possibility, the rate of hemorrhagic complications in patients who discontinued anticoagulant therapy briefly in the perioperative period was comparable to that of both control patients and those who continued to take anticoagulants What Is the Risk of Thromboembolic Complications During Brief Perioperative Discontinuation of Warfarin or Aspirin? Critical to the rational comparison of risks and benefits associated with perioperative management of anticoagulant therapy is a reliable estimate of the frequency of thrombotic complications associated with perioperative discontinuation of anticoagulant therapy. Although calculation of this frequency relies on several assumptions, substantial thrombotic complications may be associated temporally with discontinuation of anticoagulant therapy. 1 In a recent survey, 168 cutaneous surgeons described thrombotic events in 46 patients in whom anticoagulants, including aspirin and warfarin, were discontinued perioperatively. 1 Thrombotic events included cerebrovascular accidents, myocardial infarctions, and deep venous throm-

3 1394 boses, and 3 events resulted in death. An incidence calculation estimated the frequency of thrombotic complications among patients in whom anticoagulant therapy was discontinued perioperatively as 1 event per 12,816 procedures. The incidence of thrombotic complications related to discontinuation of warfarin was calculated at 1 event per 6219 procedures, and that related to discontinuation of aspirin was calculated at 1 event per 21,448 procedures. For comparison, published data estimate the rate of background thromboembolism for the most common indications (atrial fibrillation and mechanical heart valve) while a patient is taking warfarin for 2 days (the estimated time anticoagulation is absent after withdrawal of warfarin) at 1 per 11,500 procedures, 11 approximately half the calculated incidence for patients who discontinue warfarin perioperatively. The rate of background thromboembolism for the most common indications (coronary artery disease and angina) while a patient is taking aspirin for 2 days (the estimated time anticoagulation is absent after withdrawal of aspirin) was estimated at 1 per 9490 procedures, 12 approximately twice the calculated incidence for patients who discontinue aspirin perioperatively. The calculated incidence of background thromboembolic episodes in patients taking aspirin is higher than that of thromboembolic complications in patients not taking aspirin, which suggests that the incidence data are not highly accurate. These findings do not diminish the importance of other evidence that suggests that continuation of anticoagulants during cutaneous surgery is advisable. The figure calculated for thrombotic complications secondary to discontinuation of warfarin is similar to that calculated in a review that estimated 1 thrombotic event in 6250 to 12,500 procedures. 13 This figure assumes that a patient has a normal thrombotic potential for approximately 1 to 2 days when warfarin is discontinued 4 days preoperatively and resumed on the day of surgery. 11 Another recent review provided a much higher estimate of risk for thrombosis in patients discontinuing warfarin perioperatively, between 1 per 278 and 1 per 1250 procedures. 14 Given the imprecision of the calculated incidence rates, it is impossible to infer a causal relationship between discontinuation of anticoagulant therapy and occurrence of thrombotic events. However, the close temporal relationship between discontinuation of anticoagulant therapy and the occurrence of thrombotic events suggests a causal link. Small published case series support the notion that lifethreatening and lethal thromboembolic complications can occur during a period of brief perioperative discontinuation of anticoagulant therapy. 2,15-23 One case series described 2 of 10 patients with prosthetic valves who underwent surgery after discontinuing warfarin and heparin and who developed major perioperative thromboembolic complications. 24 Data from other specialties also support occurrence of thromboembolic events associated with discontinuation of anticoagulant therapy. 25 These incidence calculations challenge the conclusions of early case series that reported no thromboembolic complications among more than 100 patients who underwent surgery without heparinization after discontinuing warfarin. 26,27 Case series involving 100 patients cannot adequately characterize events estimated to occur once in 6219 procedures. 5. What Is the Relative Magnitude of Complications Associated With Continuation or Discontinuation of Warfarin or Aspirin in the Perioperative Period? The magnitude of hemorrhagic complications of cutaneous surgery is not comparable to that of thrombotic events. In the most extreme cases, hematoma formation after cutaneous surgery may result in skin necrosis, reoperation, scarring, and infection, all of which are treatable without appreciable long-term sequelae. In contrast, severe thrombotic complications associated with withdrawal of anticoagulant therapy may include stroke, myocardial infarction, and even death. It is instructive to consider hypothetically how many hematomas are acceptable to avoid a single catastrophic thrombotic event, such as stroke. Once again, however, this point is moot because no evidence suggests that hemorrhagic complications occur more frequently with continuation of anticoagulant therapy during cutaneous surgery. 6. Do Warfarin and Aspirin Exert Objectively Measurable Adverse Effects During Cutaneous Surgery? Surgeons strongly believe that they can detect warfarin or aspirin consumption by noting the degree of intraoperative oozing, despite the lack of objective evidence to support this contention. Among 168 cutaneous surgeons, 72% believed they could predict anticoagulant status by intraoperative visual inspection. 28 However, consumption of warfarin or aspirin does not result in any measurable physiologic abnormalities during cutaneous surgery. In a recent blinded study designed to test this contention, the ability of surgeons to predict anticoagulant therapy status was poor, regardless of whether the medication was warfarin, aspirin, or vitamin E. Among 43 patients who were taking a blood thinner, surgeons correctly surmised anticoagulant consumption in only 16.3%. Furthermore, the level of training of the blinded evaluators had no bearing on accuracy. These results were supported by an earlier study that showed that surgeons correctly surmised aspirin status in only 51% of equal numbers of aspirin-consuming and control patients undergoing coronary artery bypass graft operations. 29 The results of these blinded studies contrast with those of an unblinded

4 Mayo Clin Proc, November 2003, Vol 78 Perioperative Anticoagulant Therapy 1395 study in which physicians reported increased intraoperative oozing among patients taking warfarin. 6 When formulating treatment recommendations, results of blinded studies take precedence over those of unblinded studies. 7. Does the Evidence Suggest That Warfarin or Aspirin Should Be Continued or Discontinued During Cutaneous Surgery? Because complications associated with cutaneous surgery are both mild and infrequent, even in patients who take warfarin or aspirin, discontinuing these medications perioperatively is unlikely to reduce the incidence of adverse events. To my knowledge, no reports of patients experiencing life-threatening complications related to anticoagulant therapy during cutaneous surgery have been published. In contrast, evidence is substantial that, although uncommon, severe thromboembolic complications, including death, may be associated with brief perioperative discontinuation of warfarin or aspirin. Thus, when balancing benefits and risks of continuing vs discontinuing medications perioperatively, existing data support continuing medically necessary warfarin and aspirin throughout cutaneous surgery. To do otherwise may expose patients unnecessarily to increased risks of potentially life-threatening thromboembolic complications. DATA FROM OTHER SPECIALTIES Recent literature is replete with recommendations from other specialties to continue warfarin therapy during surgical procedures, based on both the lack of increased hemorrhagic complications and the potential for thrombotic events. Dental procedures, including prosthetics, endodontics, restorations, extractions, and hygiene, are among the procedures for which recommendations have been made to continue anticoagulant therapy during the perioperative period to avoid thromboembolic complications. 25,30 Ophthalmic procedures, including cataract surgery, vitreoretinal surgery, and trabeculectomy, can be performed successfully in patients who continue taking warfarin ,31-35 Even in more invasive procedures such as transurethral prostatectomy and cardiac surgery, continuation of warfarin has been recommended. 36,37 Literature on continuation of medically necessary aspirin in the perioperative period is less robust; however, reports in ophthalmologic and urologic journals suggest that continuation of aspirin is rational and without undue hemorrhagic risks. 38,39 Although controversial, continuation of aspirin has been recommended in patients undergoing urgent coronary artery bypass graft surgery because the increased risk of perioperative bleeding is outweighed by the survival benefit of managing patients with unstable angina and myocardial infarction with aspirin. 29,40,41 CAVEATS Several caveats are in order. First, concluding recommendations in this article apply to cutaneous surgery only and may not be relevant to procedures in which deeper planes of dissection are required, including postseptal periorbital surgery or subfascial facial plastic and reconstructive surgery. Second, although the unanimity of findings regarding the lack of hemorrhagic complications in the 6 studies summarized in Table is encouraging, the number of cases analyzed is insufficient to exclude the possibility of a severe perioperative complication related to anticoagulant therapy. However, given the low incidence of severe but transient complications in these reports, studies with larger numbers of patients would be unlikely to uncover any clinically meaningful differences in complications. Third, although the large number of closely temporally related thromboembolic complications associated with discontinuation of anticoagulant therapy suggests a probable causal relationship, the data are uncontrolled, and these complications may occur at a similar rate in patients continuing anticoagulant therapy. Without a large controlled trial, this possibility is difficult to prove. Guidelines cannot adequately address the particulars of all patient scenarios. Clinical judgment has a role in the consideration of all relevant patient care factors and the decision to continue or discontinue anticoagulant therapy perioperatively. Patients have varying levels of thromboembolic risk, and procedures have variable levels of invasiveness and hence hemorrhagic risk. Therefore, discontinuation of anticoagulant therapy during cutaneous surgery remains an option. Data are insufficient regarding newer antiplatelet agents, such as ticlopidine or clopidogrel, to consider them in the formulation of treatment recommendations. 16 RECOMMENDATIONS The following guidelines should be considered in decisions to continue or discontinue anticoagulant therapy during the perioperative period in patients undergoing cutaneous surgery. For patients taking warfarin (presumed medically necessary), (1) therapy should be continued throughout the cutaneous surgical procedure and (2) the international normalized ratio should be within the accepted therapeutic range on the most recent determination to avoid supratherapeutic levels. For patients taking aspirin, (1) if not medically necessary (ie, it is being used for primary prevention or pain), surgeons may choose to continue or discontinue the medication and (2) if medically necessary (ie, it is being used for secondary prevention in patients with a history of coronary artery disease, transient ischemic attack, or

5 1396 stroke), it should be continued perioperatively unless the anticipated procedure involves deep tissue resection or dissection. For patients taking any anticoagulants, intraoperative hemostasis should be maintained and effective postoperative pressure bandages used to reduce the risk of postoperative hemorrhage. In all cases, the individual patient s medical history and risk factors should be taken into account when making this clinical decision, and deviation from the guidelines should be considered if clinical imperatives warrant. Much of the data supporting perioperative maintenance of anticoagulant therapy during cutaneous surgery has been published in the dermatologic and plastic surgery literature. However, as noted in the survey by Kovich and Otley, 42 primary care physicians are involved in the decision in half the patients undergoing cutaneous operations. Thus, primary care physicians should be familiar with the compelling data that suggest that anticoagulant therapy should be continued during cutaneous surgery. REFERENCES 1. Kovich O, Otley CC. Thrombotic complications related to discontinuation of warfarin and aspirin therapy perioperatively for cutaneous operation. J Am Acad Dermatol. 2003;48: Stone LS, Kline OR Jr, Sklar C. Intraocular lenses and anticoagulation and antiplatelet therapy. J Am Intraocul Implant Soc. 1985;11: James DN, Fernandes JR, Calder I, Smith M. Low-dose aspirin and intracranial surgery: a survey of the opinions of consultant neuroanaesthetists in the UK. Anaesthesia. 1997;52: Goldsmith SM, Leshin B, Owen J. Management of patients taking anticoagulants and platelet inhibitors prior to dermatologic surgery. J Dermatol Surg Oncol. 1993;19: Otley CC, Fewkes JL, Frank W, Olbricht SM. Complications of cutaneous surgery in patients who are taking warfarin, aspirin, or nonsteroidal anti-inflammatory drugs. 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J Cataract Refract Surg. 1988;14: McCormack P, Simcock PR, Tullo AB. Management of the anticoagulated patient for ophthalmic surgery. Eye. 1993;7: Roberts CW, Woods SM, Turner LS. Cataract surgery in anticoagulated patients. J Cataract Refract Surg. 1991;17: Parr NJ, Loh CS, Desmond AD. Transurethral resection of the prostate and bladder tumour without withdrawal of warfarin therapy. Br J Urol. 1989;64: Dietrich W, Dilthey G, Spannagl M, Richter JA. Warfarin pretreatment does not lead to increased bleeding tendency during cardiac surgery. J Cardiothorac Vasc Anesth. 1995;9: Assia EI, Raskin T, Kaiserman I, Rotenstreich Y, Segev F. Effect of aspirin intake on bleeding during cataract surgery. J Cataract Refract Surg. 1998;24: Ala-Opas MY, Gronlund SS. Blood loss in long-term aspirin users undergoing transurethral prostatectomy. Scand J Urol Nephrol. 1996;30: Holden MP. Dangers of aspirin before cardiac surgery [letter]. BMJ. 1992;305: Rawitscher RE, Jones JW, McCoy TA, Lindsley DA. 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