• Bleed and Clot Concerns in the Anticoagulated Patient

    By Annie Stuart, Contributing Writer

    This article is from February 2008 and may contain outdated material.

    Many of the patients encountered by today’s eye surgeon have been placed on anticlotting drugs by another physician. The resulting challenge in surgery is to stave off both hemorrhage and emboli.

    Heart disease is the leading cause of death for both men and women in the United States. With the incidence of obesity ballooning here and in many other countries, the number of patients on antithrombotic medications, such as warfarin, clopidogrel and ticlopidine, is skyrocketing. Worldwide, dollar sales of antithrombotics more than doubled from 1999 to 2004; half this growth was in the United States.1 That does not even include over-the-counter anticoagulants—aspirin, NSAIDs, even vitamin E or ginkgo biloba—which could make the numbers all the more striking.

    What are the ramifications for the ophthalmic surgeon treating a patient who is—or should be—on anticoagulant therapy? They revolve around a complex, delicate calibration: weighing the risk of poorly controlled bleeding vs. the risk of a thromboembolic event. In other words, the ophthalmologist must balance the potential loss of eyesight against the potential loss of life. Not a small mission.

    “It’s a significant quagmire for anyone doing surgery,” said Steven V. L. Brown, MD, associate professor of phthalmology at Rush University in Chicago, especially as cardiologists become more aggressive in their reliance on anticoagulation.

    No single algorithm for blood thinners. In many cases, no formal practice guidelines exist for managing anticoagulation decisions between medical specialties. This is largely true for one reason, said Oliver D. Schein, MD, MPH, professor of ophthalmology at the Wilmer Eye Institute in Baltimore: With the extremely varied medical circumstances of patients and relatively low rates of adverse events, randomized trials comparing continuation with discontinuation of antithrombotic agents are not feasible. Deciding how to manage these risks must rest instead upon reviewing the literature and extrapolating as best you can, said Dr. Schein. In essence, it puts the onus on the surgeon to proactively collaborate with both patient and internist or cardiologist—making case-by-case decisions.

    Three Good Vascular Questions

    The primary issues to consider in these patients are the purpose of the anticoagulation, the level of risk for both ocular bleeding and systemic thrombosis, and the type of surgery being performed.

    Why alter clotting physiology? “It’s important to know why the patient is on anticoagulants,” said John W. Shore, MD, who is in private oculoplastics practice in Austin, Texas, and who is director and chairman of the risk management committee at the Ophthalmic Mutual Insurance Company. “Sometimes patients themselves don’t know why, or they may simply say, ‘I was reading The Wall Street Journal where they said it was good to take an aspirin a day.’” In cases like the latter, the medication can more easily be stopped, he said.

    At the other end of the spectrum, however, are patients who have thrombogenic stents that warrant anticoagulants as a preventive. “If you take them off without checking with the cardiologist, you can have a downstream event,” said Dr. Shore. Even drug-eluting stents have been found to increase the risk for thrombosis.2 “Cardiologists are putting their feet down and not allowing surgeons to take them off for elective surgery during the 12 months following implantation,” said Dr. Shore. Other patients on antithrombotics like warfarin may have deep venous thrombosis, atrial fibrillation or valvular disease—all predisposing them to throwing clots.3

    Who is at what risk? Classified into groups according to thrombotic risk, some patients need more anticoagulation than others, requiring that they be followed more closely or making them poor candidates for elective surgery, said Dr. Shore. A patient with a prior embolus, for example, would be at very high risk compared with one who has cardiomyopathy without atrial fibrillation, according to a protocol produced by the University of Washington.4

    A history of bleeding disorders can’t be overlooked, as well as other comorbid conditions that might contribute to slow clotting, such as abnormal kidney function or liver disease,5 according to Yoash R. Enzer, MD, clinical assistant professor of surgery at Brown University in Providence, R.I. Dr. Enzer described a patient with moderate kidney failure whose oozing continued for several weeks following oculoplastic surgery.

    What kind of surgery? Many types of ophthalmic surgeries are considered lower risk for bleeding, especially those with smaller incisions, a variety of anesthesia options, smaller needles and those procedures of short duration.6 “In most cases, cataract surgery and vitreoretinal surgery can be done without discontinuing anticoagulation,” said Dr. Brown. “But anterior segment surgery, in particular corneal transplantation and glaucoma surgery, are at higher risk for hemorrhage.” He added that those concerns apply to major eyelid and orbital surgeries as well.

    Dr. Schein agreed that the “literature is solid” concerning cataract surgery. “You’re more likely to cause a systemic problem if you interrupt anticoagulation with warfarin for a patient with an important indication for anticoagulation, such as a recent history of thrombosis, than to cause vision problems from bleeding.” Dr. Schein, author of the Academy’s Preferred Practice Pattern: Cataract in the Adult Eye, was also coauthor of a 2003 study that examined 19,283 cataract surgeries conducted over a two-year period that concluded, “Among routine users of anticoagulants or antiplatelet agents, there was no evidence to suggest that patients who continued use were at increased risk of ocular hemorrhagic events, nor that those who discontinued use were at increased risk of medical events for which these medications are routinely prescribed.”7

    For those concerned about bleeding, however, two measures may help minimize adverse effects, said Dr. Schein. “Use topical anesthesia alone or a sub-Tenon’s injection with a blunt cannula.” He noted that some internists and cardiologists in the community are “frustrated by cataract surgeons who insist that anticoagulants be stopped because it puts patients through gyrations involving bridging of different anticoagulation strategies and exposes them to risk as the whole clotting system is affected.”

    Questions linger outside of cataract surgery, however. Dr. Shore asked, “Is it safe to proceed with intraocular surgery with the patient on Coumadin? There’s no right answer. I wouldn’t necessarily say that there are intraocular procedures that will alter your approach each and every time. You can’t just rely on one standard of care. Age, eye history, many things come into play. This all puts the surgeon in a precarious position.” Oculoplastic surgeons, especially, are often operating in highly vascularized areas, and tend to face higher risks of bleeding than do other types of ophthalmic surgeons, especially compared with cataract specialists.

    Your Choice: To Thin or Not to Thin

    Though more common than thrombosis, bleeding is often more of a nuisance for patients and surgeons than a serious life-altering event, said Nicholas J. Butler, MD, ophthalmology resident at Brown University and coauthor of a recent survey now in prepublication, “Current Practice Patterns of Anticoagulation Management in Oculofacial Plastic Surgery.”8 One aspect of this survey of oculoplastic surgeons looked at how they manage oral anticoagulants in three main categories of surgery: eyelid surgeries, invasive lacrimal procedures such as dacryocystorhinostomy, and orbit surgeries. These categories are worrisome for hemorrhage-causing vision loss, and invasive lacrimal procedures are the most likely to cause profuse bleeding, said Dr. Enzer, another coauthor of the study. “You can lose a unit of blood very quickly,” he said, “but most of the time it can be controlled.”

    Hemorrhage: Not a small concern. A major fear with antithrombotics is the potential for vision loss, said Dr. Butler. “If you use a retrobulbar block, you add the risk of retrobulbar hemorrhage, which can lead to compartment syndrome and can compromise blood flow to the optic nerve.”

    Embolism: Quite a large concern. Despite these worries, Dr. Enzer concedes that the survey results caused him to do an about-face by highlighting a disproportionate concern over hemorrhagic events when compared with the life-altering impact of thromboembolic events, such as stroke or myocardial infarction. “I had thought that people were not stopping their anticoagulants for a long enough time period,” he said, referring to adequate coagulation recovery after the drugs are discontinued. What he found instead focused his attention in a different direction. “Thirty-six percent of my colleagues—based on memory alone—had witnessed at least one to three thromboembolic events in the previous 10 years.” And yet 77 percent vs. 23 percent of surgeons surveyed were still more concerned with perioperative hemorrhage than with a serious thromboembolic event.

    Patients don’t like blood or bruising. In addition to looming fears about orbital compartment syndrome, high patient expectations may be partly what’s influencing oculoplastic surgeons, said Dr. Butler. “You don’t want to have a patient coming in for a cosmetic procedure and end up with a lot of postoperative bruising and potentially large hematomas that may take weeks and weeks to resolve,” he said.

    Regulating the Risks

    Dr. Shore, in fact, contends that the risk of bleeding isn’t being overestimated. Admitting a potential bias due to seeing a preponderance of these cases, he said they’re not as uncommon as one might think. The surgeons most complacent and potentially vulnerable, he said, may be those with a high volume—those who do repetitive procedures day in and day out. “Unless the staff is trained to identify those at high risk for bleeding,” said Dr. Shore, “they can slip through the cracks.”

    Although surgeons may not reach consensus about these issues any time soon, most can agree on some essential, proactive steps that can lower the inherent risks of the anticoagulated patient facing surgery.

    1. Review. A thorough history is critical, especially because many factors can influence the dose-response relationship of antithrombotics. In addition to older age and male gender, which are associated with increased bleeding rates, these are a few of the factors to consider when assessing bleeding and clotting risks before surgery:

    • History of cerebrovascular disease, recent myocardial infarction, atrial fibrillation, heart valve, cardiac stent, peripheral vascular disease, deep vein thrombosis or pulmonary embolism;
    • History of serious comorbid conditions, such as renal failure, liver disease or severe anemia;
    • Fever, which may increase intensity of anticoagulation;
    • History of prescription anticoagulation and over-the-counter medication use;
    • Duration of anticoagulation, risk being highest during the first 90 days;
    • Indication for anticoagulation, with risk being highest for arterial thromboembolism or ischemic cerebrovascular disease;
    • History of bleeding disorders or thrombogenic cancer; and
    • Use of homeopathic remedies, herbal supplements, vitamins, teas or foods that affect clotting function.

    “Patients don’t consider homeopathic or herbal supplements as medications, but they can have a powerful anticoagulant effect,” said Dr. Enzer. “Even foods, such as certain mushrooms eaten frequently in some Asian communities, or herbal teas, can have a strong impact.” Drs. Enzer and Butler’s survey found that more than half of surgeons reported that more than 50 percent of the time patients failed to mention the use of herbal remedies prior to surgery.

    Dr. Shore also emphasized the importance of tracking blood pressure—before, during and after surgery. When elevated, it increases the risk for bleeding, particularly during oculoplastic surgery.

    2. Consult. Even with a thorough evaluation, collaboration with the internist or cardiologist is indispensable in most cases. If anticoagulation is being used only as a prophylactic, the surgeon can likely manage the case, said Dr. Enzer. But if anticoagulation is absolutely required, it’s in the best interests of the patient to work closely with the “gatekeeper of care.”

    “In my experience, the way people get into trouble is when decisions are made without discussion and documentation,” said Dr. Schein. “My feeling is that anticoagulants should only be stopped for routine cataract surgery with the input of the internist or cardiologist.”

    A discussion with the patient is not enough, agreed Dr. Shore. “A patient may believe he should be stopping an anticoagulant and then have a perioperative stroke,” said Dr. Shore, who sends a form to the cardiologist or internist, saying, “Here’s our plan. If you disagree, let us know your recommendation.”

    “The internist has a very important role,” said Dr. Butler. “For anybody who has a complicated enough medical history that requires being on any kind of antiplatelet or anticoagulant, we should at least have a chart review done by, or telephone conversation with, the internist.”

    3. Advise. Once a surgical plan is in place, the surgeon must discuss and document the potential risks—both bleeding and thromboembolic—with the patient. It’s critical to document in writing the risks for an embolus, a stroke or even death, said Dr. Brown.

    With their survey Drs. Enzer and Butler found, instead, that the majority of oculoplastic surgeons fail to have patients sign a consent form to stop anticoagulants, suggesting that patients may not be fully informed of potentially devastating consequences from stopping.

    Surgeons can ensure patient understanding by providing written instructions about stopping and restarting antithrombotics. And they should verify that the patient has stopped medications as needed and advise the patient about potential symptoms of bleeding and related complications, as well as what to do if they occur. Communicating the medication history and plan to the anesthesiologist and surgical team is further insurance for lowering risk.

    4. Reconsider. In some cases, postponing surgery may be the only option. For example, surgery must be avoided, if possible, for at least 12 months after implantation of drug-eluting stents and for at least one month after implantation of bare-metal stents.9 In other cases, consultation with the cardiologist or internist will provide the best guide.

    Coagulation Stop and Start

    Thrombocytes, wake up. In cases where discontinuing antithrombotics is warranted, they may be stopped before surgery with oversight from the cardiologist or internist. Following are general guidelines that may require tailoring, depending upon each case:

    • Warfarin (Coumadin).This is a complex drug to manage, and stopping and resuming it may expose patients to a hypercoagulable state. After discontinuation, it takes several days for the antithrombotic effect to recede and, when resumed, several days to become reestablished.3 In general, warfarin is stopped about four to five days prior to elective surgery. If discontinued, close monitoring is mandatory, using the international normalized ratio (INR). “We’re seeing a shift in the standard of care toward checking the INR before oculoplastic surgery,” said Dr. Shore. “It’s important to check the coagulation profile the morning of surgery during the preoperative period,” said Dr. Brown. “The numbers can change dramatically.” What about high-risk patients—those with certain types of heart valves, or with atrial fibrillation and a history of thromboembolic stroke—who can’t afford to be below the target therapeutic INR dose of 2 to 3.5 during surgery? For them, bridging with low molecular weight heparin or unfractionated heparin may reduce the risk, said Dr. Shore. “Patients like these may need to be hospitalized, placed on a heparin bridge, then stopped and managed carefully by a hematologist to ensure they get through surgery safely.”
    • Intravenous heparin. Discontinue about 12 hours before surgery.7
    • Enoxaparin sodium (Lovenox). Discontinue 12 to 24 hours before surgery. Platelet levels need to be evaluated before surgery since enoxaparin can cause thrombocytopenia.7
    • Platelet inhibitors. Aspirin, a nonreversible platelet inhibitor, is usually stopped about seven to 10 days before surgery.6 NSAIDs are reversible platelet inhibitors and may be stopped 24 to 72 hours before surgery. Recommendations may vary depending upon the type of surgery.
    • Thienopyridine agents. Commonly prescribed after coronary artery stent placement, these agents should only be stopped following advice from a cardiologist or prescribing physician. An OMIC scientific advisory recommends aspirin therapy, if possible, if thienopyridine derivatives, such as clopidogrel and ticlopidine, are discontinued, and restarting the former drugs as soon as possible.7
    • Herbal supplements and vitamins. Because these have a variety of mechanisms of action and duration of effect, it is best to consult with the prescribing physician or a pharmacist about stop times.7

    Platelets, pipe down. In most cases, warfarin can be resumed the first postoperative night, assuming there are no bleeding problems, said Dr. Butler. Depending upon hemostasis, aspirin may also be started on postoperative day one. When in doubt, ophthalmologists should consult a pharmacist to determine how long it takes for the medication to reach a therapeutic level.

    With warfarin, the risk of thromboembolism is increased for about a week during the period of discontinuation and reintroduction. “I had a patient in whom we resumed anti-coagulation one week after glaucoma surgery and who then had a delayed subchoroidal hemorrhage,” said Dr. Brown.

    Too often, no one tells the patient when to restart, said Dr. Schein. “The patient thinks, ‘I guess they’ll tell me when to restart.’” Given the risks involved, that’s an oversight no one, neither patient nor surgeon, can afford.

    1 IMS Global Insights Web site. “Antithrombotics—Current Market and Future Outlook.” www.imshealth.com/web/content/0,3148,64576068_63872702_7026

    2 Iakovou, I. et al. JAMA 2005;293:2126–2130.

    3 Kearon, C. and J. Hirsh. N Engl J Med 1997;336:1506–1511.

    4 Tan, H. “Perioperative Management of Chronic Anticoagulation.” www.depts.washington.edu/gim/clinical/MCSSyllabus/Anticoagulation.pdf.

    5 Chapman, S. and D. L. O’Connor. Pulmonary Reviews 2000;5(6): online at www.pulmonaryreviews.com.

    6 Shore, J. W. and A. M. Menke. “Hemorrhage Associated With Ophthalmic Procedures: Focus on Blepharoplasty.” Ophthalmic Mutual Insurance Company, www.omic.com/resources/risk_man/recommend.cfm#hemorrhage.

    7 Katz, J. et al. Ophthalmology 2003;110:1784–1788.

    8 Butler, N. J. et al. “Current Practice Patterns of Anticoagulation Management in Oculofacial Plastic Surgery.” Survey in prepublication.

    9 Science advisory. Circulation 2007;115:813–818.

    Meet the Experts

    Associate professor of ophthalmology, Rush University, Chicago.
    Financial disclosure: None.

    Resident physician in ophthalmology, Brown University
    Financial disclosure: None.

    Clinical assistant professor of surgery, Brown University.
    Financial disclosure: None.

    Professor of ophthalmology, Wilmer Eye Institute.
    Financial disclosure: None.

    In private practice in Austin, Texas, and director and chairman of the risk management committee at the Ophthalmic Mutual Insurance Company.
    Financial disclosure: None.