COSMETIC Practical Guidelines for Venous Thromboembolism Chemoprophylaxis in Elective Plastic Surgery Matthew L. Iorio, M.D. Mark L. Venturi, M.D. Steven P. Davison, D.D.S., M.D. Seattle, Wash.; and Washington, D.C.
Summary: Venous thromboembolism is a complication that results in a wide range of patient morbidity and potential mortality. Awareness of this risk has led to recent advances in both the perioperative planning of chemoprophylaxis and the stratification of risk factors. Together, these modifications have helped reduce the incidence and severity of venous thromboembolism. Major hospital-based initiatives to decrease the overall rate of venous thromboembolism and halt the progression of severe complications, including pulmonary embolism, are one such change. However, surgeon reluctance based on the potential for bleeding complications continues to decrease the use of these algorithms, despite several reports that fail to demonstrate an increase in postoperative bleeding or hematoma formation with chemoprophylaxis administered at appropriate dosages. This review summarizes the current recommendations and procedure-specific strategies for venous thromboembolism prophylaxis with a focus on elective or aesthetic surgery–based procedures. The authors will recommend which patients are appropriate, what doses are appropriate, and when the doses should be administered for aesthetic and elective surgery. (Plast. Reconstr. Surg. 135: 413, 2015.)
T
he basis of venous thromboembolism chemoprophylaxis is to prevent the untoward complications associated with thrombus and embolus formation and to minimize bleeding complications. However, it has been suggested that in some procedures the risk of hematoma may outweigh the benefits of chemoprophylaxis, especially in elective surgery, although the risk of bleeding may be largely mitigated by the appropriate use of prophylaxis. In addition, as an estimated 2 million cases of deep vein thrombosis occur in the United States annually, with 350,000 to 600,000 of those cases converting to pulmonary embolus with a resultant 100,000 to 200,000 deaths, each patient should be evaluated carefully for venous thromboembolism risk factors and strategies of prevention.1 Despite multiple high-quality studies demonstrating benefit, chemoprophylaxis continues From the Division of Plastic Surgery, University of Washington Medical Center; the Department of Plastic Surgery, Georgetown University Medical Center; and DAVinci Plastic Surgery. Received for publication April 9, 2014; accepted May 20, 2014. Copyright © 2015 by the American Society of Plastic Surgeons DOI: 10.1097/PRS.0000000000000908
to be underused throughout plastic surgery.2 In addition, venous thromboembolism has been cited as reasonably preventable and is part of the Centers for Medicare & Medicaid Services reimbursement policies inclusion into the list of “never events.”3 Broughton et al. demonstrated in a survey of 1557 plastic surgeons that only 48.7 percent performing rhytidectomies, 43.7 percent performing liposuction, and 60.8 percent performing a combined procedure used any sort of venous thromboembolism prophylaxis.4 Strategies for prevention are extensive and are based on a combination of disease-specific risk factors generated from data based on procedure-type and patient comorbidities. It is the goal of this review to summarize the available evidence and provide practical applications and recommendations for patients undergoing all types of elective and aesthetic plastic surgery procedures. This article focuses on addressing evidence-based answers to key problems:
Disclosure: The authors have no financial interests in any of the products or techniques mentioned and have received no external support related to this study.
www.PRSJournal.com
413
Plastic and Reconstructive Surgery • February 2015 1. In elective plastic surgery, is a procedurebased or patient risk factor–based model applicable? 2. What procedures are at higher or lower risk for venous thromboembolism and how do we modify these recommendations? 3. What type and respective dose of chemoprophylaxis are appropriate? 4. What is the ideal timing of prophylaxis for elective aesthetic plastic surgery?
MECHANISM OF ACTION A basic understanding of the coagulation cascade and pharmacology is beneficial when considering venous thromboembolism chemoprophylaxis regimens. The end product of this cascade, in both the extrinsic and intrinsic pathways, is the common route of thrombin and fibrin activation (factor I). The activation of prothrombin to thrombin, and the successive cleavage of fibrinogen into fibrin, serves as a substrate to bind platelets and form thrombus. Arterial thrombus is a product of platelet aggregates bound together by a small amount of fibrin, usually as a result of vessel damage,1 whereas venous thrombi are composed of a large volume of fibrin, with intermixed amounts of red blood cells and scattered platelets. Agents for the prevention of arterial thrombogenesis are based on platelet dysregulation.5 Venous clots can be formed rather quickly and suddenly in comparison, and represent a response to a fixed or transient episode of stasis, turbulence, or vessel injury. As such, fibrinolytic agents are the main mechanism of chemoprophylaxis against venous thrombogenesis. Heparin and low-molecular-weight heparin target similar pathways within the coagulation cascade by blocking activated factor X and thrombin. Heparin binds indiscriminately to both targets within the coagulation cascade and plasma proteins, with the potential for nonhemorrhagic complications such as heparin-induced thrombocytopenia.1 In comparison, low-molecularweight heparin has a higher affinity for binding and inactivating factor Xa, thereby decreasing the rate of plasma protein binding and increasing low-molecular-weight heparin bioavailability.1,5 This explains the less frequent dosing cycle of low-molecular-weight heparin in comparison with unfractionated heparin, the more predictable dose-response, and the less frequent need for coagulation monitoring. The next generation of chemoprophylaxis is based on agents that selectively target single
414
elements within the cascade, such as initiation, propagation, or fibrin formation.5 Multiple drugs are being actively developed and investigated; however, the most frequently cited of the group is fondaparinux (Arixtra; GlaxoSmithKline, London, United Kingdom). This medication inhibits propagation of factor Xa and is packaged in selfinjection, single-use syringes, with a typical dose administered of 2.5 mg daily. Orthopedic and general surgery trials have demonstrated a superior rate of venous thromboembolism prevention with fondaparinux in comparison with low-molecular-weight heparin, notably in joint replacement or hip fracture indications, when given between 6 and 8 hours after surgery. An earlier postoperative dosing time has demonstrated a reduction in the efficiency of fondaparinux, with a higher rate of postoperative bleeding and hematoma formation.5–7 An oral direct reversible selective factor Xa inhibitor, apixaban (Eliquis; Bristol-Myers Squibb, New York, N.Y.), has been available in Europe since May of 2011 and is currently U.S. Food and Drug Administration approved for atrial fibrillation.8 No indications exist for surgery patients yet; however, oral dosing may simplify acceptance and compliance. A nonreversible oral rivaroxaban factor Xa (Xarelto; Janssen Pharmaceuticals, Leverkusen, Germany) is approved for deep vein thrombosis prophylaxis in joint replacement. It appears to have higher efficacy, but with a potentially higher bleeding risk as compared with low-molecularweight heparin.8 In comparison with chemoprophylaxis techniques, mechanical measures for prophylaxis are based on decreasing venous stasis and vein distention. Paradoxically, pneumatic compression pumps offer an additional element of chemoprophylaxis through the stimulation of fibrinolytic activity in veins by reducing plasminogen activator 1, and by increasing the release of plasminogen activator.5,9 In this way, if both lower extremities are in the operative field, one or both of the upper extremities could have mechanical compression devices applied with some preserved prophylactic benefit. The majority of deep vein thrombi are thought to originate during the transient venous stasis of induction, although 56 percent of venous thromboembolisms will present in a delayed fashion following patient discharge to home.10 Mechanical therapies are therefore optimized by their application 30 minutes before induction and continued until the patient is ambulatory.
Volume 135, Number 2 • Venous Thromboembolism Chemoprophylaxis CURRENT DATA AND RECOMMENDATIONS There are two major approaches to the stratification of risk for surgical patients; one component is the patient and the other is the procedure. For example, total hip arthroplasty prophylaxis can be regarded as a procedure-driven approach, given the regional vascular injury and immobilization with the potential for venous thromboembolism propagation in every case of hip arthroplasty. A recent compendium by the American College of Chest Physicians11 has moved to a procedurebased assessment. In comparison, Caprini is a major proponent of patient risk stratification,12 and models based on this concept are known collectively as the Caprini risk-assessment score. Using patient risk stratification, the American Society of Plastic Surgeons Venous Thromboembolism Task Force identified strategies for venous thromboembolism risk reduction based on an evaluation of the available literature. The Caprini risk-assessment score is based on an aggregate risk score generated by the presence or absence of 39 individual risk factors.13 This model is a major proponent of patient risk stratification and scores patients in low-, moderate-, high-, and very-highrisk groups. A patient with a score of 4 to 5 is at increased risk of venous thromboembolism, and a score above 8 indicates a very high risk. The Task Force generated grade B recommendations for adult patients undergoing aesthetic procedures with general anesthesia and referred surgeons to the 2005 Caprini risk factor assessment tool to stratify and treat individual patients (Figs. 1 and 2). They cited their use of the 2005 Caprini scale as a reference point, given the formal validation for stratifying plastic surgery patients based on their individual risk factors.14,15 In comparison, Pannucci et al. investigated the validity of the updated 2010 Caprini Risk Assessment Model compared with the 2005 version, given the addition of several new risk factors and reweighting of previous factors (Fig. 3). This included additional subcategorizations for body mass index, operative time, and cancer risk factors.13 The Venous Thromboembolism Prevention Study database was used to compare the two risk-assessment tools’ ability to accurately predict 60-day venous thromboembolism risk. Three thousand three hundred thirty-four patients were evaluated with the two risk-stratification methods, with the benefit of matched controls, given the identical study populations. This demonstrated a higher median 2010 Caprini score compared with the 2005 Caprini score (p < 0.001). This
was attributable to the three-fold increase in the stratification inclusion of super-high-risk patients in the 2010 paradigm, with observed differences in 60-day thromboembolism rates per other subgroup classifications between the two models. This reflects a trend that, with time, more patients are being considered higher risk and need chemoprophylaxis, which may reflect overscoring. In an effort to delineate the risk of postoperative bleeding complications with chemoprophylaxis, Pannucci et al. evaluated outcomes for 1567 patients that had received low-molecular-weight heparin in a postoperative setting in comparison with 2114 control patients.2 Patients were included if they met moderate- to high-risk stratification with a Caprini score of greater than or equal to 3, general anesthesia, and postoperative admission. Prophylaxis was based on 40 mg subcutaneously daily, or 30 mg subcutaneously daily for patients with a body mass index greater than 40 kg/m2. Among both groups, breast surgery patients had the highest rate of postoperative hematoma (p
Summary: Venous thromboembolism is a complication that results in a wide range of patient morbidity and potential mortality. Awareness of this risk has led to recent advances in both the perioperative planning of chemoprophylaxis and the stratification of risk factors. Together, these modifications have helped reduce the incidence and severity of venous thromboembolism. Major hospital-based initiatives to decrease the overall rate of venous thromboembolism and halt the progression of severe complications, including pulmonary embolism, are one such change. However, surgeon reluctance based on the potential for bleeding complications continues to decrease the use of these algorithms, despite several reports that fail to demonstrate an increase in postoperative bleeding or hematoma formation with chemoprophylaxis administered at appropriate dosages. This review summarizes the current recommendations and procedure-specific strategies for venous thromboembolism prophylaxis with a focus on elective or aesthetic surgery–based procedures. The authors will recommend which patients are appropriate, what doses are appropriate, and when the doses should be administered for aesthetic and elective surgery. (Plast. Reconstr. Surg. 135: 413, 2015.)
T
he basis of venous thromboembolism chemoprophylaxis is to prevent the untoward complications associated with thrombus and embolus formation and to minimize bleeding complications. However, it has been suggested that in some procedures the risk of hematoma may outweigh the benefits of chemoprophylaxis, especially in elective surgery, although the risk of bleeding may be largely mitigated by the appropriate use of prophylaxis. In addition, as an estimated 2 million cases of deep vein thrombosis occur in the United States annually, with 350,000 to 600,000 of those cases converting to pulmonary embolus with a resultant 100,000 to 200,000 deaths, each patient should be evaluated carefully for venous thromboembolism risk factors and strategies of prevention.1 Despite multiple high-quality studies demonstrating benefit, chemoprophylaxis continues From the Division of Plastic Surgery, University of Washington Medical Center; the Department of Plastic Surgery, Georgetown University Medical Center; and DAVinci Plastic Surgery. Received for publication April 9, 2014; accepted May 20, 2014. Copyright © 2015 by the American Society of Plastic Surgeons DOI: 10.1097/PRS.0000000000000908
to be underused throughout plastic surgery.2 In addition, venous thromboembolism has been cited as reasonably preventable and is part of the Centers for Medicare & Medicaid Services reimbursement policies inclusion into the list of “never events.”3 Broughton et al. demonstrated in a survey of 1557 plastic surgeons that only 48.7 percent performing rhytidectomies, 43.7 percent performing liposuction, and 60.8 percent performing a combined procedure used any sort of venous thromboembolism prophylaxis.4 Strategies for prevention are extensive and are based on a combination of disease-specific risk factors generated from data based on procedure-type and patient comorbidities. It is the goal of this review to summarize the available evidence and provide practical applications and recommendations for patients undergoing all types of elective and aesthetic plastic surgery procedures. This article focuses on addressing evidence-based answers to key problems:
Disclosure: The authors have no financial interests in any of the products or techniques mentioned and have received no external support related to this study.
www.PRSJournal.com
413
Plastic and Reconstructive Surgery • February 2015 1. In elective plastic surgery, is a procedurebased or patient risk factor–based model applicable? 2. What procedures are at higher or lower risk for venous thromboembolism and how do we modify these recommendations? 3. What type and respective dose of chemoprophylaxis are appropriate? 4. What is the ideal timing of prophylaxis for elective aesthetic plastic surgery?
MECHANISM OF ACTION A basic understanding of the coagulation cascade and pharmacology is beneficial when considering venous thromboembolism chemoprophylaxis regimens. The end product of this cascade, in both the extrinsic and intrinsic pathways, is the common route of thrombin and fibrin activation (factor I). The activation of prothrombin to thrombin, and the successive cleavage of fibrinogen into fibrin, serves as a substrate to bind platelets and form thrombus. Arterial thrombus is a product of platelet aggregates bound together by a small amount of fibrin, usually as a result of vessel damage,1 whereas venous thrombi are composed of a large volume of fibrin, with intermixed amounts of red blood cells and scattered platelets. Agents for the prevention of arterial thrombogenesis are based on platelet dysregulation.5 Venous clots can be formed rather quickly and suddenly in comparison, and represent a response to a fixed or transient episode of stasis, turbulence, or vessel injury. As such, fibrinolytic agents are the main mechanism of chemoprophylaxis against venous thrombogenesis. Heparin and low-molecular-weight heparin target similar pathways within the coagulation cascade by blocking activated factor X and thrombin. Heparin binds indiscriminately to both targets within the coagulation cascade and plasma proteins, with the potential for nonhemorrhagic complications such as heparin-induced thrombocytopenia.1 In comparison, low-molecularweight heparin has a higher affinity for binding and inactivating factor Xa, thereby decreasing the rate of plasma protein binding and increasing low-molecular-weight heparin bioavailability.1,5 This explains the less frequent dosing cycle of low-molecular-weight heparin in comparison with unfractionated heparin, the more predictable dose-response, and the less frequent need for coagulation monitoring. The next generation of chemoprophylaxis is based on agents that selectively target single
414
elements within the cascade, such as initiation, propagation, or fibrin formation.5 Multiple drugs are being actively developed and investigated; however, the most frequently cited of the group is fondaparinux (Arixtra; GlaxoSmithKline, London, United Kingdom). This medication inhibits propagation of factor Xa and is packaged in selfinjection, single-use syringes, with a typical dose administered of 2.5 mg daily. Orthopedic and general surgery trials have demonstrated a superior rate of venous thromboembolism prevention with fondaparinux in comparison with low-molecular-weight heparin, notably in joint replacement or hip fracture indications, when given between 6 and 8 hours after surgery. An earlier postoperative dosing time has demonstrated a reduction in the efficiency of fondaparinux, with a higher rate of postoperative bleeding and hematoma formation.5–7 An oral direct reversible selective factor Xa inhibitor, apixaban (Eliquis; Bristol-Myers Squibb, New York, N.Y.), has been available in Europe since May of 2011 and is currently U.S. Food and Drug Administration approved for atrial fibrillation.8 No indications exist for surgery patients yet; however, oral dosing may simplify acceptance and compliance. A nonreversible oral rivaroxaban factor Xa (Xarelto; Janssen Pharmaceuticals, Leverkusen, Germany) is approved for deep vein thrombosis prophylaxis in joint replacement. It appears to have higher efficacy, but with a potentially higher bleeding risk as compared with low-molecularweight heparin.8 In comparison with chemoprophylaxis techniques, mechanical measures for prophylaxis are based on decreasing venous stasis and vein distention. Paradoxically, pneumatic compression pumps offer an additional element of chemoprophylaxis through the stimulation of fibrinolytic activity in veins by reducing plasminogen activator 1, and by increasing the release of plasminogen activator.5,9 In this way, if both lower extremities are in the operative field, one or both of the upper extremities could have mechanical compression devices applied with some preserved prophylactic benefit. The majority of deep vein thrombi are thought to originate during the transient venous stasis of induction, although 56 percent of venous thromboembolisms will present in a delayed fashion following patient discharge to home.10 Mechanical therapies are therefore optimized by their application 30 minutes before induction and continued until the patient is ambulatory.
Volume 135, Number 2 • Venous Thromboembolism Chemoprophylaxis CURRENT DATA AND RECOMMENDATIONS There are two major approaches to the stratification of risk for surgical patients; one component is the patient and the other is the procedure. For example, total hip arthroplasty prophylaxis can be regarded as a procedure-driven approach, given the regional vascular injury and immobilization with the potential for venous thromboembolism propagation in every case of hip arthroplasty. A recent compendium by the American College of Chest Physicians11 has moved to a procedurebased assessment. In comparison, Caprini is a major proponent of patient risk stratification,12 and models based on this concept are known collectively as the Caprini risk-assessment score. Using patient risk stratification, the American Society of Plastic Surgeons Venous Thromboembolism Task Force identified strategies for venous thromboembolism risk reduction based on an evaluation of the available literature. The Caprini risk-assessment score is based on an aggregate risk score generated by the presence or absence of 39 individual risk factors.13 This model is a major proponent of patient risk stratification and scores patients in low-, moderate-, high-, and very-highrisk groups. A patient with a score of 4 to 5 is at increased risk of venous thromboembolism, and a score above 8 indicates a very high risk. The Task Force generated grade B recommendations for adult patients undergoing aesthetic procedures with general anesthesia and referred surgeons to the 2005 Caprini risk factor assessment tool to stratify and treat individual patients (Figs. 1 and 2). They cited their use of the 2005 Caprini scale as a reference point, given the formal validation for stratifying plastic surgery patients based on their individual risk factors.14,15 In comparison, Pannucci et al. investigated the validity of the updated 2010 Caprini Risk Assessment Model compared with the 2005 version, given the addition of several new risk factors and reweighting of previous factors (Fig. 3). This included additional subcategorizations for body mass index, operative time, and cancer risk factors.13 The Venous Thromboembolism Prevention Study database was used to compare the two risk-assessment tools’ ability to accurately predict 60-day venous thromboembolism risk. Three thousand three hundred thirty-four patients were evaluated with the two risk-stratification methods, with the benefit of matched controls, given the identical study populations. This demonstrated a higher median 2010 Caprini score compared with the 2005 Caprini score (p < 0.001). This
was attributable to the three-fold increase in the stratification inclusion of super-high-risk patients in the 2010 paradigm, with observed differences in 60-day thromboembolism rates per other subgroup classifications between the two models. This reflects a trend that, with time, more patients are being considered higher risk and need chemoprophylaxis, which may reflect overscoring. In an effort to delineate the risk of postoperative bleeding complications with chemoprophylaxis, Pannucci et al. evaluated outcomes for 1567 patients that had received low-molecular-weight heparin in a postoperative setting in comparison with 2114 control patients.2 Patients were included if they met moderate- to high-risk stratification with a Caprini score of greater than or equal to 3, general anesthesia, and postoperative admission. Prophylaxis was based on 40 mg subcutaneously daily, or 30 mg subcutaneously daily for patients with a body mass index greater than 40 kg/m2. Among both groups, breast surgery patients had the highest rate of postoperative hematoma (p
