The Need for Venous Thromboembolism (VTE) Prophylaxis in Plastic Surgery

Transcription

1 Continuing Medical Education Article Patient Safety The Need for Venous Thromboembolism (VTE) V. Leroy Young, MD; and Marla E. Watson, MA Dr. Young is in private practice in St. Louis, MO. Ms. Watson is a clinical researcher associated with the same practice. This article, which represents a critically important analysis of the topic of venous thromboembolism (VTE), was commissioned by the Patient Safety Steering Committee of the American Society for Aesthetic Plastic Surgery (ASAPS). As part of its mission, this committee is embarking on a series of campaigns and projects focusing on specific patient safety topics in aesthetic surgery. These campaigns will be designed not only to educate ASAPS members but also to involve related organizations so that nurses, office staff, and our other partners in patient care can work together with us to create an integrated Culture of Safety. The committee s first campaign focuses on the prevention of VTE and has been timed to coordinate with national DVT Awareness Month and the Aesthetic Society s participation in the Coalition to Prevent DVT. ASAPS commitment to patient safety is represented by the Culture of Safety symbol shown above. The triangle represents both safety and the Aesthetic Society, the orange color is a universally recognized signal for caution and safety, and the word culture reflects our belief that patient safety is an ongoing concern that must permeate every level of care provided by the aesthetic surgery team. Beginning on January 1, 2005, ASAPS and the American Society of Plastic Surgeons (ASPS) instituted a Patient Safety CME requirement of 20 credits for their members, to be fulfilled over a 3-year cycle. One Patient Safety CME credit can be obtained by completing the examination that follows this article. Learning Objectives: The reader is presumed to have a broad understanding of plastic surgical procedures and concepts. After studying this article, the participant should be able to: 1. Identify the risk factors for VTE. 2. Differentiate between active and passive mechanical prophylaxis. 3. Explain the risks and benefits of anticoagulant prophylaxis. Physicians may earn 1 AMA PRA Category 1 credit credit by successfully completing the examination based on material covered in this article. The examination begins on page 176. ASAPS members can also complete this CME examination online by logging onto the ASAPS Members-Only Web site ( and clicking on Clinical Education in the menu bar. Little has been published about venous thromboembolism (VTE) complications in plastic surgery. The authors investigated the recent literature, particularly literature reviews and meta-analyses of clinical studies, in order to outline strategies for prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) applicable to plastic surgery patients. Major risk factors for VTE include trauma, a prior history of VTE, older age, use of oral contraceptives or hormone replacement therapy, and prolonged travel. Although the frequency of VTE among plastic surgery patients is estimated to be from The authors have no financial disclosures with respect to the content of this article. A ESTHETIC S URGERY J OURNAL ~ MARCH/APRIL

2 less than 1% to 2% of cases, in fact many of our patients are at moderate to high risk of VTE. Moreover, the actual frequency of VTE among plastic surgery patients is probably higher than we know, because up to two thirds of cases are asymptomatic. Mechanical methods of VTE prophylaxis include graduated compression stockings (GCSs), intermittent pneumatic compression (IPC) devices, and venous foot pumps (VFPs). They are recommended primarily for patients with a high risk of bleeding or as an adjunct to chemoprophylaxis. Intermittent pneumatic compression devices were found to be more effective than passive compression using GCSs. For plastic surgery patients, IPC devices or VFPs are recommended for any procedure that lasts more than 1 hour, and for all patients receiving general anesthesia. Use should begin 30 to 60 minutes before surgery. Low-molecular-weight heparin (LMWH) is the most widely used form of DVT/PE prophylaxis. Other forms of chemoprophylaxis are coming onto the market or under development. In particular, fondaparinux, an indirect FXa inhibitor, was approved in 2004 for VTE prophylaxis in orthopedic surgery. Studies have indicated that it is significantly more effective than LMWH after joint replacement, hip fracture surgery, and in cancer patients. Other drugs in development include idraparinux, another indirect FXa inhibitor, direct FXa inhibitors, and several direct thrombin inhibitors. Plastic surgeons have generally been reluctant to use antithrombotic agents because of the increased risk of bruising or hematoma and the possible need for blood transfusion. However, numerous studies have found little or no increase in the frequency of clinically important bleeding associated with their use. Some plastic surgeons now routinely use chemoprophylaxis in patients undergoing abdominoplasty, combined procedures, or procedures lasting more than 4 hours. The authors also recommend postoperative chemoprophylaxis in circumferential body contouring, thighplasty, surgery requiring open space dissection, transverse rectus abdominus muscle (TRAM) procedures, and surgical procedures likely to contribute to venous stasis or compression. It is impractical and expensive to screen every patient for asymptomatic DVT. A patient history focusing specifically on VTE risk factors should be performed within a few weeks of surgery. Patient education should include information about the symptoms of DVT and PE (including the fact that most patients with VTE are asymptomatic) and a full explanation of the risks and benefits of anticoagulant prophylaxis. (Aesthetic Surg J 2006;26: ) Many plastic surgeons have become increasingly aware of the need for prevention of venous thromboembolytic (VTE) events in their patients, even though the reported incidence of VTE in our specialty is low. This disease process includes both deep vein thrombosis (DVT) and pulmonary embolism (PE), both of which may have fatal or debilitating consequences. The low incidence of VTE reported in the plastic surgery literature is not necessarily a reflection of good medicine. In 2001, the American Society of Plastic Surgeons (ASPS) reviewed the existing reported data and estimated that 18,000 cases of DVT may occur each year in plastic surgery patients. 1 That kind of number makes more of an impact than citing a percentage of 1% or 0.3% for VTE in a small patient series. First, consider that the first symptom of a PE is too often sudden death. Even if a PE does not cause death or a DVT resolves, the patient may be left with long-term disability. Then think about the fact that more than half of plastic surgeons responding to an ASPS survey said they use no form of DVT prophylaxis for their patients. 1 The death of a patient who comes for an elective procedure is a nightmare for any plastic surgeon. Even worse is the possibility that someone in our care will die, not because of something we did, but because of something simple we did not do. The professional societies of many surgical and medical specialties are raising awareness of serious VTE complications among their members, and plastic surgeons are part of this process. Since the late 1990s, the medical and surgical literature has witnessed an explosion of reviews, clinical studies, and meta-analyses of the problem of VTE in the United States. We have much to learn in light of all the evidence-based studies that stress the importance of preventing VTE in all surgical patients. The overriding conclusion of these studies is that surgeons are putting their patients at risk for DVT or PE because prophylaxis is either nonexistent, not the appropriate method, or not continued long enough. A result of all this activity is the growing number of consensus statements being developed regarding VTE prophylaxis and treatment. 2-7 Consensus reports emerge through meetings of experts from a variety of medical specialties who review the current literature and pool their knowledge to produce guidelines and recommendations. Other publications present clinical algorithms for the diagnosis of VTE The most influential set of guidelines has been developed by the American College of Chest Physicians (ACCP), which updates its recommendations every few years through its Conference on Antithrombotic and Thrombolytic Therapy. 2 The ACCP guidelines, which form the basis of 158 Aesthetic Surgery Journal ~ MARCH/APRIL 2006 Volume 26, Number 2

3 other consensus reports, are widely regarded as a national standard of medical care. According to the clinical evidence on which consensus statements are based, most plastic surgery patients need VTE prophylaxis. Furthermore, many should receive anticoagulation medications for some portion of the perioperative period. The rationale for this statement should become apparent through the following brief discussions of VTE incidence and etiology, and the latest consensus on risk factors that demand prophylaxis. Guidelines are presented related to the categorization of patients according to risk factors and how they inform implementation of the most highly regarded preventive methods. Also discussed are improvements in the education of both plastic surgeons and their patients, and the evidence related to bleeding when chemoprophylaxis is used. The diagnosis and treatment of VTE are beyond the scope of this article. Because the literature on this topic is so extensive, publications since the year 2000, especially literature reviews and meta-analyses of clinical studies, served as the primary sources for this article. Very few publications from plastic surgeons are available, and clinical studies within our patient population are nonexistent. Incidence of VTE Precise incidence figures for DVT and PE are difficult to pin down, with different authors citing different rates. Part of the problem is that much of the literature focuses on the incidence of confirmed VTE: people diagnosed through imaging studies or autopsy. Naturally, most diagnoses follow symptomatic presentation, yet many patients with a DVT or PE have no symptoms. It is believed that only about one third of patients with DVT experience the classic signs and symptoms, so the possibility of DVT is not likely to be investigated in the remaining two thirds. 6 We do not know how many cases of occult or asymptomatic PE or DVT might occur. The relationship between silent DVT and later development of symptomatic DVT or PE is not well understood, but autopsy studies have revealed important information. In an autopsy investigation of medical and surgical patients, the cause of death was PE in 10% of 2388 patients. 15 Of this PE group, 83% had DVT in the legs at the time of death, yet only 19% had been symptomatic and just 3% had been investigated for DVT. Among those who died of PE, 24% had undergone surgery within a mean of 6.9 days before death. A metaanalysis of PE revealed that DVT was suspected in only 18% of patients with confirmed PE. 16 Another study found that the mortality rate for PE is about 30% without treatment; moreover, two thirds of patients with PE remain undiagnosed. 17 In an analysis of population studies, White 18 determined that the incidence of first-time symptomatic VTE in the United States, standardized for age and sex, ranged from 71 to 117 cases per 100,000 population (approximately 1:1000), with about one third having PE and two thirds manifesting DVT. White s study has been adopted by the American Heart Association, which estimates that more than 200,000 new cases of VTE occur each year. Of these, 30% die within 1 month of diagnosis, including the 20% in whom sudden death occurs due to PE. 19 White s analysis also revealed that the incidence of first-time VTE rises exponentially with age, particularly after age 40. The most dramatic increase occurs after age 70, with the incidence being 10-fold higher among those in their 70s compared to people aged 25 to 35 years. No clear gender differences seem to exist, but racial differences are evident, with the VTE incidence 2.5 to 4 times higher in whites and African Americans than in Hispanics and Asians. 18 People with a DVT or PE have a greatly increased risk of developing a second one. Studies consistently report recurrent VTE frequencies of 7% to 13% within 1 year, 20% to 22% within 5 years, and around 30% at 8 and 10 years. 18 The frequency is higher among cancer patients. The majority of second VTE events are of the same type as the first; more than 75% of a second DVT followed a DVT, and more than 65% of recurrent events after PE were PE. 18 Paying attention to VTE prophylaxis is also important for prevention of postthrombotic syndrome (PTS), which typically develops between 5 to 10 years after DVT. As many as 40% to 80% of DVT patients may have this syndrome in a mild or severe form. 9 When clots do not embolize or dissolve, the residual clots and related venous hypertension can destroy valves and produce this syndrome, which is characterized by persistent edema, leg discomfort, sclerosis, dermatitis, and stasis ulcers. The result is sometimes substantial disability. 20 Venous hypertension and dilatation also can cause periods of painful swelling in the affected leg, which makes PTS difficult to distinguish from DVT. The incidence of VTE following surgical procedures and/or hospitalization varies by surgery type and illness severity. The ACCP panel compiled the statistics in Table 1 based on objective diagnostic testing for DVT in patients not receiving thromboprophylaxis. 2 (Because distal DVTs are more difficult to diagnose with noninvasive testing, one can only imagine how many DVTs were not The Need for Venous Thromboembolism (VTE) A ESTHETIC S URGERY J OURNAL ~ MARCH/APRIL

4 Table 1. Absolute risk of DVT in hospitalized patients* DVT Patient group prevalence % Medical patients General surgery Major gynecologic surgery Major urologic surgery Neurosurgery Stroke Hip or knee arthroplasty/hip fracture surgery Major trauma Spinal cord injury Critical care patients From Geerts et al, 2 with permission. *Based on objective diagnostic testing for DVT in patients who did not receive prophylaxis. identified.) The large range in the rates for each category reflects results from the different studies, using different protocols, and focused on hospitalized patients. The length of hospitalization is unknown but may be as short as 1 night for some procedures. Plastic surgery is probably most comparable to general surgery. Reported DVT incidences in some types of surgery have special relevance to plastic surgery, including bariatric surgery and abdominal surgery. Obesity has long been recognized as a major risk factor for VTE, and PE following gastric bypass surgery (GBS) occurs in 2.4% of patients, with 0.21% of these PEs being fatal. 21,22 An autopsy study of 10 GBS patients determined that 30% died of PE and 80% had microscopic evidence of PE. 23 This may relate to the fact that a perioperative hypercoagulable state follows some GBS procedures, both open and laparoscopic surgery. 24 Specifically, plasminogen, antithrombin III, and protein C levels decrease, while levels of fibrinogen, prothrombin fragment 1.2, and thrombin-prothrombin complex increase. Because of the danger of VTE in bariatric surgery patients, 95% of surveyed members of the American Society for Bariatric Surgery have reported using routine prophylaxis in their patients, and 48% say that they have had at least 1 fatal PE among their patients. 25 The preferred preventive methods are intermittent pneumatic compression (IPC) among 33% of surgeons and chemoprophylaxis among 63%. Before body contouring procedures are performed on GBS patients, it seems prudent to check with their bariatric surgeons to learn what sort of DVT prophylaxis they received and how they responded. The duration of body contouring procedures and difficulty with mobility after surgery suggest that DVT prevention is especially important in this group of patients. Higher rates of VTE in patients undergoing abdominal surgery have been well documented. 2 Abdominal surgery encompasses a wide range of surgery types, including cancer removal, hysterectomy, and cholecystectomy. The higher incidence of VTE in abdominal surgery is believed to relate to disruption of lowerextremity venous return during surgery or injury to pelvic veins. A review of 30 studies of various chemoprophylaxis agents used in abdominal surgery determined that low-dose unfractionated heparin (LDUH) and lowmolecular-weight heparin (LMWH) prevented about 50% of PE cases and about 65% of DVT cases in this patient population. 26 VTE in Plastic Surgery Patients The frequency of VTE among plastic surgery patients is far from clear, though most studies report a rate of less than 1% to about 2% This is a small percentage, but it translates into significant numbers of real people. Davison and colleagues 31 looked at the 1.1% DVT and 0.8% PE rates reported in a series of abdominoplasty patients 28 and calculated that this represents 644 cases of DVT and 468 cases of PE (based on 2001 statistics of plastic surgery procedures). Davison et al calculated that the 0.35% risk of DVT reported in a study of face lifts 27 represented 485 individuals, with the 0.14% frequency of PE translating into 199 cases. Abdominoplasty alone has a higher risk of VTE than other plastic surgery procedures, in the range of 1.4% to 2%. 28,32 When abdominoplasty is combined with other procedures, the incidence for PE has been reported as high as 6.6%. 33 Even more alarming, Aly and colleagues 34 reported a 9.4% rate of PE in belt lipectomy patients. We should expect VTE rates to be higher in body contouring patients who undergo quite lengthy procedures under general anesthesia. In fact, the incidence of PE rises to 3.5% in obese and bariatric patients, even when using prophylaxis that includes heparin. 29 Furthermore, rates are likely to be higher when procedures are combined, in part because of the longer duration of surgery. A survey of board-certified plastic surgeons collected data on 496,000 lipoplasty patients and determined the mortality rate from lipoplasty to be about 1 in every 160 Aesthetic Surgery Journal ~ MARCH/APRIL 2006 Volume 26, Number 2

5 5000 procedures. 35 The largest percentage of deaths (23%) resulted from pulmonary embolus. This type of survey data collection is less than ideal, especially since almost 30% of those surveyed did not respond. Other mortality studies have determined that when lipoplasty is combined with other procedures, mortality rises from 1:47,415 surgeries to 1:7, According to The Doctors Company, 36 a significant proportion of that increased mortality may be due to PE. Reported frequencies of DVT and PE in patients undergoing large-volume lipoplasty range from 0% to 1.1% Another survey of board-certified plastic surgeons asked about the incidence of VTE in face lift patients. 27 Of those surgeons surveyed, 80% responded with information on 9937 face lift procedures. For the year studied, 0.35% patients developed a DVT and 0.14% had a PE. Furthermore, 1 of 9 surgeons reported either a DVT or PE (with 1 fatality) in their face lift patients. Of the DVT and PE cases reported, 83.7% occurred in patients who received general anesthesia versus local/intravenous sedation. The other significant finding was that 59% of VTE occurred in patients who received no prophylaxis, 37% in those who received elastic compression stockings or Ace wrappings, and 4% in patients who had intermittent compression devices. Of the surgeons surveyed, 61% said they did not use prophylactic measures in face lift patients. It is unwise to think that surgery remote from the lower extremities is unlikely to lead to VTE. A prospective study of major trauma and VTE incidence without prophylaxis found that 50% of patients with injuries to the head, chest, or abdomen developed VTE in the legs, as did 54% of patients with head injuries. 40 Before venography studies were performed, only 3 of 201 patients with confirmed DVT had clinical features suggestive of DVT. Others have reported on VTE in other plastic surgery procedures, including 1.3% with DVT in breast reconstruction with a transverse rectus abdominis muscle (TRAM) flap, 41 and 0.3% for VTE in a head and neck surgery series. 42 Older patient age and the lack of prophylaxis with mechanical devices were strongly associated with the VTE that occurred in the head and neck study. The data regarding plastic surgery reports of VTE are few and far between, and all reports are either retrospective patient series reviews or based on surveys of surgeons. We may not know much about the frequencies of VTE in plastic surgery procedures, but we do know that our patients are not immune from this serious complication. Furthermore, as more patients seek plastic surgery and surgeons perform more complex and/or combined procedures, the frequency is likely to rise unless routine prophylactic measures are adopted. Etiology of VTE A detailed description of how and why DVT develop is outside the scope of this article, but both arterial and venous thrombosis develop when the body s procoagulant, anticoagulant, and fibrinolytic factors are out of balance. 43 Whereas arterial clots primarily result from vascular disease and take time to progress to the serious stage of myocardial infarction or stroke, venous thrombosis is characterized by its suddenness, often in reaction to an acute and transient event. The hemostatic system must maintain blood in a fluid state so it can circulate; at the same time, it must be able to convert blood into an insoluble gel when vascular injury occurs. 44 This is accomplished through 2 interlocking systems: platelets and coagulation proteins. During clot formation, a series of chemical processes take place some in sequence and some simultaneously to activate or inactivate a multitude of coagulation proteins and other chemicals. Our understanding of venous thromboembolism dates back to 1859, when the German pathologist Rudolf Virchow outlined the 3 major factors he believed caused VTE. Today, what has come to be known as the Virchow triad of thrombus formation still applies: (1) venous stasis caused by a change in blood flow or volume; (2) vessel wall damage caused by inflammation or injury; and (3) hypercoagulability. 43 Only 1 or 2 parts of the triad are necessary for a thrombus to develop. Venous stasis probably plays the major role in thrombus formation related to surgery. Stasis is not a factor in arterial thrombosis because the pumping action of the heart propels blood through the arteries. DVT arises when the return flow is impaired. Both anesthesia and immobilization cause venous stasis, as do supine and flexed positions. When venous return from the lower extremities is slowed during surgery, the decreased blood flow prevents the activated clotting factors from clearing as quickly as they would normally. Venous thrombi tend to form behind the venous valve cusps, as well as in the intramuscular sinuses of the calf veins. 8 The second factor in clot development is often damage to the innermost layer of a vein, the intima. Even though the site of injury may be microscopically small, platelets begin to collect at the intimal defect, and a coagulation cascade begins. 8 It is easy to understand how clots form after major vascular damage. Less clear The Need for Venous Thromboembolism (VTE) A ESTHETIC S URGERY J OURNAL ~ MARCH/APRIL

6 Table 2. VTE risk factors to be considered by plastic surgeons Solid, consistent evidence that these are the most important risk factors* Prior history of VTE (DVT or PE) Malignancy (active or in patient history) Thrombophilia disorders (inherited or acquired) Factor V Leiden mutation (makes factor V resistant to activated protein C) Prothrombin 20210A mutation (found exclusively in whites) Antithrombin deficiency Protein S and protein C deficiency High levels of: fibrinogen or plasminogen, factor VIII, factor IX, factor XI, thrombin activatable fibrinolysis inhibitor (TAFI), or protein C inhibitor Low levels of tissue factor pathway inhibitor (TFPI) Hyperhomocysteinemia (plasma homocysteine level >18.5 mmol/l) Dysfibrinogenemia and polycythemia vera Antiphospholipid antibodies (lupus anticoagulant and anti-cardiolipin) Obesity (risk may be highest for those <40 years of age) Use of oral contraceptives, tamoxifen, hormone replacement therapy or other estrogen-containing drugs Known to be risk factors but probably not in the top tier; do not disregard as unimportant Age 40 years (risk rises as age rises) General anesthesia (risk rises with each hour in surgery, regardless of procedure) Varicose veins Inflammatory disease (eg, inflammatory bowel disease, rheumatologic diseases, especially systemic lupus erythematosus) Abdominal surgery (carries higher risk than most other types of surgery) Pregnancy, abortion, or miscarriage within 3 months Smoking Recent hip or knee replacement or hip fracture Recent surgery of any kind Prolonged travel by air, train, or car Recent physical trauma *Important risk factors that are rarely encountered in plastic surgery practices include prolonged immobilization, ischemic stroke, heart failure, chronic lung disease, respiratory failure, serious infection, pneumonia, central venous catheter, paralysis, spinal cord injury. Some risk factors are permanent (eg, history of VTE or cancer, chronic disease, thrombophilia, age) and some are transient (eg, surgery, travel, estrogen use, pregnancy). is their development during surgery. Intimal damage can occur during dilatation and stretching of muscles, cavities, or openings. Surgical manipulation of patient position, compression, or vessel traction are other possibilities. The vasodilatory effect of anesthesia also plays a role. Stretching muscles and tissues, and therefore the veins within them, is certainly not uncommon in plastic surgery procedures, and some degree of minor vessel injury seems likely. Hypercoagulation disorders are unlikely to be identified in patients prior to surgery unless the patient has had specific blood tests, has a family history of bleeding disorders, or previously experienced a VTE. A large number of coagulation disorders are either acquired or inherited. Three of the most common inherited disorders are deficiencies of protein C, protein S, or antithrombin III. 9,45 Factor V Leiden, present in about 5% of whites, is the most common genetic prothrombotic defect 43,45,46 Hypercoagulation occurs because factor V is resistant to inactivation by activated protein C (APC). The prothrombin 20210A genetic mutation, which increases prothrombin levels, is found only in people of European descent and is relatively common, appearing in 2% to 3% of this population. Elevated levels of procoagulant factors also raise the risk for thrombosis, but whether they are inherited or acquired is unclear. These include fibrinogen and the factors II, VIII, IX, and XI. 43 Other blood and coagulation disorders that increase VTE risk appear in Table Aesthetic Surgery Journal ~ MARCH/APRIL 2006 Volume 26, Number 2

7 During surgery, 1, 2, or all 3 elements of Virchow s triad may be present and initiate the coagulation cascade. Perhaps half of DVTs associated with surgery begin intraoperatively, and many may spontaneously resolve. 47 Perioperative chemoprophylaxis (given before surgery in the case of LMWH or after surgery in the case of fondaparinux) breaks up these DVTs; when treatment is continued, new thrombi are prevented from forming. Most DVTs associated with surgery begin in the deep calf veins. However, superficial thrombi should not be discounted because they can extend into the deep system. Imaging studies have determined that superficial phlebitis involves the deep system in almost one quarter of patients. 48 About half of calf DVTs that develop because of surgery will resolve spontaneously within 3 days or so. 47 Although screening tests have found that as many as 75% of calf thrombi are clinically silent and remain isolated in distal veins, between 15% to 35% of distal DVTs eventually propagate to the proximal veins and may embolize if not treated. 2,47 This usually occurs within 1 week of calf symptom development. 47 By the time a patient has symptoms of calf DVT, as many as 89% already have proximal DVT. 49 Consequently, DVT prophylaxis has 2 objectives: (1) to prevent DVT from forming in the deep calf veins, and (2) to reduce the risk that calf thrombosis will extend proximally. Proximal DVT is an occlusion at or above the popliteal vein, which may continue its proximal extension into the iliofemoral system from which the great majority of PEs arise. Although most proximal DVTs first develop in the calf, isolated DVT can also develop in pelvic veins, especially in abdominal surgeries. 47 Proximal extension is more likely when risk factors that contributed to the DVT formation continue after surgery, or when the initial occlusion is large. It is believed that most episodes of symptomatic proximal DVT progress to PE, though signs of PE may be absent. Most patients with symptomatic proximal DVT but no chest symptoms will have evidence of PE on ventilation-perfusion lung scans. 47 Furthermore, about 70% of patients with symptomatic PE have DVT (with or without symptoms), usually involving a proximal vein. Approximately 10% of symptomatic PE are fatal within 1 hour of symptom onset. 47 To complicate matters further, asymptomatic PE in patients with asymptomatic DVT are not uncommon in patients who do not receive prophylaxis. 47 The period of highest risk for fatal PE is within 3 to 7 postoperative days. Thus, any patient with symptoms of proximal DVT must be diagnosed immediately, although treatment should begin before diagnosis if DVT is suspected. Fortunately, compression ultrasonography has high specificity (96%) and sensitivity (95%) for diagnosis of DVT at or above the popliteal vein when performed by an experienced examiner. 6,13 Ultrasound is less reliable for distal DVT, but contrast venography is very effective. 6 Symptomatic and/or confirmed proximal DVT demand anticoagulation treatment with heparin or fondaparinux followed by a vitamin K antagonist (VKA), such as warfarin, for at least 3 to 6 months. It is impractical and expensive to screen every patient for asymptomatic DVT. Perhaps the best we can do is use the most appropriate method of prophylaxis for each patient. As discussed briefly in the previous section, recurrent VTE events are a serious problem, and patients who have one DVT or PE are a much greater risk of having another one and require long-term anticoagulation therapy. The goal should be to prevent a first VTE event. Many of our patients are young and healthy when we operate on them. They are having elective procedures. It should be the responsibility of plastic surgeons to safeguard their health and not compromise their future health by putting them at risk for VTE. Risk Factors for VTE A combination of risk factors and the type of surgery predispose to VTE. A list of risk factors is presented in Table 2. (Every risk factor listed will not be discussed here.) Each patient requires some degree of individualized evaluation to assess whether he or she possesses risk factors beyond the major risk of surgery. Risk factors may be transient or chronic, acquired or inherited. Evaluating risk is more complicated than assigning a number value to each risk factor and adding them up. Some risk factors are cumulative, but others that interact together may increase a patient s risk exponentially. There is broad consensus in the literature that the risk of VTE rises in proportion to the number of predisposing factors. 45 A review of symptomatic DVT patients determined that 24% of people with 1 risk factor had DVT, in comparison to 50% with 3 risk factors. 50 In another study, 100% of patients with objective evidence of DVT had 5 risk factors. 45 Trauma patients are at high risk for VTE, and plastic surgeons do get involved in trauma repairs. The VTE risk is highest for people who have hip or leg fractures. However, 40% of patients with traumatic injuries to the face, chest, or abdomen have been found to form DVT in the legs. 40 The risk of VTE arising from surgery is lower than the risk association between VTE and cancer. Patients The Need for Venous Thromboembolism (VTE) A ESTHETIC S URGERY J OURNAL ~ MARCH/APRIL

8 with a malignancy have a 2 to 6 times higher risk for VTE. 45,51 This is especially true for advanced cancers of the breast, lung, brain, prostate, ovary, pancreas, and gastrointestinal tract. 51 Administration of chemotherapy further increases the risk. Women with breast cancer undergoing chemotherapy and surgery have a 3-fold increase in VTE risk compared to women undergoing surgery alone. In some patients, DVT is the first symptom of cancer. One investigation of patients with bilateral DVT found that 26% were diagnosed with cancer following the DVT diagnosis, and 70% of these patients already had metastatic disease. 52 The risk for VTE associated with cancer does not disappear with cure. It is probably not as high as when surgery is performed for cancer, but people considered cured or in remission are still at higher risk. Patients with a prior VTE have been found to have a risk 8-fold higher for developing a new VTE event during a subsequent high-risk period. This later high-risk period might be another surgery, pregnancy, injury, or any kind of precipitating event. 53 Thrombophilia disorders are probably most important when found in combination with other risk factors. Inherited coagulation disorders are the leading cause of VTE in juveniles. People with antiphospholipid antibodies (the lupus anticoagulant or anticardiolipin) have been found to have as much as a 5-fold increased risk of VTE development. 43,45 Those with a previous VTE have an even higher risk. Older age is strongly associated with VTE risk. Patients aged 40 and older have a significantly increased risk of VTE compared to people younger than 40, and the risk nearly doubles with each subsequent decade. 45 There is contradictory evidence regarding whether obesity alone is a risk factor for VTE, but obesity combined with surgery is frequently classified as an important risk. 45 Obese patients, in general, are likely to have more venous stasis because they are often less mobile and their venous return from the lower extremities may be slower. The problem of stasis is likely to be more pronounced during and soon after surgery. One study comparing obese with nonobese patients reported that the obese had a relative risk (RR) factor of 2.5 for DVT and 2.1 for PE. 54 Obese women had a higher RR than obese men (2.75 vs 2.02, respectively). For obese men and women younger than 40, the combined RR was 5.19 for PE and 5.20 for DVT. For obese men younger than 40, the RR for DVT was 3.71, compared to 6.1 for obese women younger than 40. For obese women younger than 40 who use oral contraceptives, the RR for DVT may be as high as 9.8. The interaction of some risk factors has been found to cause an exponential increase in a patient s risk. In one study, women aged 15 to 45 years with a body mass index (BMI) higher than 25 who took oral contraceptives had a 10-fold increased risk for VTE compared to controls. 55 In another study, the use of estrogen in combination with a coagulation disorder was investigated through genotyping 2 groups of hospitalized women aged 45 to 64 years: (1) those hospitalized for VTE, and (2) agematched controls hospitalized for reasons unrelated to VTE. When the groups were compared, the study found a 3-fold increased risk for VTE among hormone replacement therapy (HRT) users. 56 There was a 2-fold increased risk of VTE with the prothrombin mutation, and a 4-fold increased risk for those with the Factor V Leiden mutation. A small group who used HRT and were positive for Factor V Leiden had a 15-fold higher risk. It is believed that the increased risk for VTE among women who take estrogen diminishes after the first year, but this issue needs further investigation. The risk would not disappear after 1 year, so estrogen use must remain on the list of factors contributing to VTE risk. However, the use of estrogen-containing medications in the distant past does not seem to be a risk factor. The increased risk of DVT among women taking birth control pills has long been recognized. The risk is even higher among oral contraceptive users who smoke. Women on HRT, tamoxifen, and some other breast cancer drugs are also at higher risk. Increased estrogen levels contribute to thrombosis by lowering levels of protein S, and cigarette smoking enhances this tendency. 9 Women taking estrogen plus progestin with no other risk factors have been found to have a 2- to 3-fold increased risk of VTE. 56 We can assume that many plastic surgery patients, regardless of age, are taking estrogen in some form. Shortly before surgery, female patients should be asked directly about estrogen-containing drugs, so their VTE risk can be accurately assessed. Men taking estrogen therapy for prostate cancer also have a higher VTE risk. Prolonged travel in itself is a known cause of DVT and PE. Venous thromboembolism occurs because the muscle pumping action that propels venous blood back into circulation is impaired. 9 Morbid obesity causes venous stasis in much the same way. A car ride of many hours raises the risk, as does train travel, unless the person gets up and walks regularly. Air travel carries the highest risk and has even been named the economy class syndrome. Prolonged travel has been associated with a 3-fold increased risk of VTE and is even higher in the obese, users of oral contraceptives, and those with Factor V 164 Aesthetic Surgery Journal ~ MARCH/APRIL 2006 Volume 26, Number 2

9 Table 3. Risk stratification of surgical patients and VTE risk without prophylaxis* Additional risk DVT % PE % Level of risk Surgery Age (y) factors Calf Proximal Clinical Fatal Low Minor (<1 hr) <40 No <.01 Moderate Nonmajor <40 1 or more Major <40 No Nonmajor No High Nonmajor >60 No Nonmajor or more Major <40 1 or more Major 40 1 or more Very high Hip/knee Any arthroplasty, hip fracture, major trauma, spinal cord injury Major >40 Multiple, including prior VTE or cancer *Adapted from Geerts et al, 2 and Institute for Clinical Systems Improvement, 4 with permission. Leiden. 43 Those who fly for 12 hours or more carry the greatest risk, but flights of 4 hours also carry risk. In addition, the risk may be cumulative, so that more than 1 flight taken within a short period of time raises one s risk. 6 If patients are traveling some distance to have surgery that will last more than 1 hour, they should not be scheduled for surgery on the morning after a flight or long car trip, nor should they travel soon after surgery. Instead, they should spend a day or two ambulating after arrival and before departure. Frequent leg movements and good hydration seem to minimize some of the VTE risk associated with lengthy travel. Because elastic compression stockings have been found to lower DVT risk in air travel, 43 patients traveling to and from a surgical procedure should probably be advised to wear a pair during their trip. Clearly, many plastic surgery patients possess risk factors for DVT and PE before they have surgery, which is a risk factor by itself, especially when performed under general anesthesia. However, no single patient profile has emerged that will definitively state who needs prophylaxis and who does not. Consequently, we are left with our own clinical judgment. Often, the overriding question to be asked is this: do the risks of prophylaxis outweigh the risk of venous thromboembolism? Venous thromboembolytic risk factors cannot be accurately assessed without a careful patient history. Although a patient history and list of medications is obtained when we first meet our patients, time may pass before they proceed to surgery, or a procedure with an intrinsically higher risk for VTE may happen months or years after a patient s initial procedure. Because of this, a patient history that specifically focuses on VTE risk factors should be done within a few weeks before surgery. Surgeons should specifically ask patients about recent estrogen use, pregnancy, long-distance travel, injuries (especially to the legs), other surgeries, diagnosis of medical conditions, status of chemotherapy (if applicable), tobacco use, current medications, and use of over-thecounter products, including herbal supplements, some of which may alter bleeding times. Prophylaxis Working from the list of risk factors shown in Table 2, surgeons can easily categorize patients into the risk stratification scheme illustrated in Table 3. The incidences of calf DVT, proximal DVT, PE, and fatal PE that occur without prophylaxis are also presented in Table 3. These incidences were agreed on by the ACCP consensus panel and have been widely adopted by other organizations developing guidelines. Unfortunately, the term nonmajor surgery is not defined in any of the literature reviewed. The risk factors shown in Table 2 and the risk stratification of patients in Table 3 should enable surgeons to The Need for Venous Thromboembolism (VTE) A ESTHETIC S URGERY J OURNAL ~ MARCH/APRIL

10 Table 4. Recommended VTE prophylaxis for different risk levels in surgical patients Risk level Recommended prophylaxis* Dosage and timing Low Patient education AND Early and frequent ambulation Continue at home AND Flexion/extension of ankles Continue at home GCS Optional; may be used at home Moderate High Very high Same as low risk IPC if anticoagulation is not an option Continue until good ambulation LMWH (enoxaparin)** mg subcutaneously once daily; initial dose 2 hrs before surgery or 12 hrs after; continue until patient is fully ambulatory and evaluate need for longer prophylaxis OR LDUH q12h until patient is fully ambulatory Same as low risk IPC and/or GCS Until good ambulation AND LMWH (enoxaparin)** 40 mg subcutaneously once daily; initial dose 2 hrs before surgery or 12 hrs after; continue for 5-10 days OR Fondaparinux 2.5 mg subcutaneously once daily; initial dose 6-8 hrs after surgery; do not give <6 hrs postop; continue for 5-10 days Same as low risk IPC and/or GCS Until good ambulation AND LMWH (enoxaparin)** 40 mg subcutaneously once daily; initial dose 2 hrs before surgery or 12 hrs after; continue for 7-12 days and seriously consider longer prophylaxis OR Fondaparinux 2.5 mg subcutaneously once daily; initial dose 6-8 hrs after surgery; do not give <6 hrs postop; continue for 7-12 days and evaluate need for longer prophylaxis AND Longer-term prophylaxis with warfarin or If patient risk factors indicate the need for other vitamin K antagonist long-term prophylaxis, convert to warfarin at INR 2 3 *Determining the type and length of prophylaxis depends on type and length of surgery and individual risk factors of patients. **Low-molecular-weight heparins other than enoxaparin (Lovenox) will have different dosing. Low-dose unfractionated heparin cannot be used conveniently at home so it is omitted from the table for high- and very-high-risk patients, who may need to continue prophylaxis after discharge. However, it may be used for inpatients. In recent years, LMWH has emerged as the heparin of choice because it is more convenient, safe, and effective. If LDUH is used for high- or very-high-risk patients, it is administered every 8 hours. Fondaparinux has recently been approved for VTE prophylaxis in abdominal surgery. Its other indications are prophylaxis in hip fracture surgery and hip and knee replacement, and for treatment of DVT and PE. determine whether their patients are at low risk, moderate risk, high risk, or very high risk. Armed with this information, surgeons can then apply the prophylaxis guidelines in Table 4, which indicate what type of prophylaxis is recommended for each category of risk stratification. Because asymptomatic PE in patients with asymptomatic DVT is not uncommon, every surgeon must decide whether to take preventive action during the perioperative period. A conservative approach is to initiate some type of prophylaxis, at least graduated compression stockings (GCSs) or IPC devices, for almost every patient who will have a procedure that lasts 1 hour or longer or is performed under general anesthesia. This approach seems to be the minimum standard of care. Something of 166 Aesthetic Surgery Journal ~ MARCH/APRIL 2006 Volume 26, Number 2

11 a dilemma arises, however, when the issue of chemoprophylaxis enters the equation. Mechanical Prophylaxis Mechanical methods of prophylaxis GCS, IPC devices, and venous foot pumps (VFPs) have all been found to reduce DVT risk, though not to the same degree as chemoprophylaxis. 2 Furthermore, no study has definitively shown that compression devices reduce the risk of proximal DVT, PE, or fatal PE, which are the complications we most want to prevent. 2 The ACCP guidelines recommend that mechanical prophylaxis be used primarily in patients at high risk of bleeding or as an adjunct to anticoagulants. Graduated compression stockings (GCSs) are a passive method of prophylaxis. They help prevent DVT by reducing the overall cross-sectional area of the leg, increasing the velocity of venous flow, improving valve function, and reducing distention of the vein wall. 57 Some studies have found that use of GCS reduced the rate of DVT by about 50% to 64% in general surgery patients, but the risk reduction was much greater when chemoprophylaxis was added to the regimen. 2,57 For maximum efficacy, stockings should be properly fitted to patients, who need to be educated about how to put them on properly. Intermittent pneumatic compression devices and VFPs are active mechanical methods of prophylaxis. When compared to no prophylaxis, a meta-analysis of 16 surgical studies found that IPC devices reduced the risk of DVT by 60%. 58 Intermittent pneumatic compression devices are believed to work through a combination of actions: relieving venous stasis by actively pumping blood, stimulating fibrinolytic activity in the veins by reducing plasminogen activator 1, and increasing release of tissue plasminogen activator. 59 The study of VTE in face lift patients 27 mentioned previously found a significant decrease in DVT when IPC devices were used versus passive compression or no prophylaxis. Consequently, IPC devices are recommended over elastic stockings. Both types of mechanical prophylaxis may be used simultaneously. Ace bandages cannot be wrapped to achieve graduated compression and are therefore not recommended. The use of mechanical devices such as IPCs or VFPs should never impede a patient s ability to ambulate, and aggressive ambulation by the evening of surgery or next morning is a critical component of DVT prevention. The nurses caring for patients who stay overnight in hospitals or surgical centers should be thoroughly educated about the importance of DVT prophylaxis. Removal of IPCs will be something of an inconvenience for the staff, but it must be done so that patients can begin ambulating on their own. When not ambulating, the IPCs need to be put back on until the patient is sent home. Chemoprophylaxis Heparins The most widely-used effective method of DVT/PE prophylaxis is heparin, in the form of either LMWH or LDUH. Both forms inactivate 2 important factors in the coagulation cascade: factor Xa and factor IIa (thrombin). One advantage of LMWH over unfractionated heparin is that LMWH binds less with plasma proteins; because of this, LMWH has greater bioavailability. 5,46,60 Low-dose unfractionated heparin more readily binds with circulating plasma proteins and other types of cells; as a result, higher doses are often needed to reach therapeutic levels, and patients must be monitored to ensure therapeutic levels are maintained. Because of its greater bioavailability, LMWH has a more predictable dose response. It can be given less frequently because it has a longer plasma half-life and slower rate of clearance. It is easy to understand why LMWH has become the heparin of choice among most surgeons. Unlike LDUH, LMWH can be given once daily and requires no coagulation monitoring to confirm correctness of dosage. Furthermore, since LMWH does not bind to platelets as much as LDUH, the chance of developing heparin-induced thrombocytopenia (HIT) is reduced with LMWH. 2 The HIT risk is eliminated altogether with the new nonheparin drug fondaparinux (Arixtra) Both LDUH and LMWH significantly reduce the rates of symptomatic VTE, but LMWH has been shown to be significantly more effective in reducing asymptomatic DVTs. 2 Low-molecular-weight heparin also may cause less major bleeding and hematoma than LDUH. Some studies that have directly compared LDUH with LMWH found significantly fewer wound hematomas and other bleeding complications with LMWH, but other studies found the opposite. 2 The critical factor seems to be LMWH dose. When LMWH (eg, enoxaparin, dalteparin, or tinzaparin) is given at the higher dose of more than 3400 U daily, there are more hematomas or other bleeding complications than when the LMWH dose is 3400 U or less daily. For very-high-risk patients, the higher dose is recommended. For patients using a self-contained dosing regimen, Lovenox is typically given once at the 30- or 40-mg dosage, although increased bleeding may occur at the higher dosage. 2 The Need for Venous Thromboembolism (VTE) A ESTHETIC S URGERY J OURNAL ~ MARCH/APRIL