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Deep Venous Thrombosis Prophylaxis for Total Joint Arthroplasty: American Academy of Orthopaedic Surgeons Guidelines
The Journal of Arthroplasty Vol. 23 No. 7 Suppl. 1 2008
Deep Venous Thrombosis Prophylaxis for Total Joint Arthroplasty: American Academy of Orthopaedic Surgeons Guidelines Javad Parvizi, MD, FRCS, Khalid Azzam, MD, and Richard H. Rothman, MD, PhD
Abstract: The orthopedic community continues to face a challenge with regard to the prevention of thromboembolism after total joint arthroplasty. The first and foremost issue facing surgeons is how to select the best agent or modality that is effective in preventing the untoward consequences of thromboembolism without causing other complications that can have dire consequences. Other challenges include the uncertainty regarding the dose and duration of various agents, the value of mechanical prophylaxis alone, and the exact end points that should be used to measure the efficacy of prophylaxis. This article discusses some of the recent developments in prevention and management of thromboembolism after total joint arthroplasty, in particular highlighting the guidelines that were developed by American Academy of Orthopedic Surgeons. Key words: total joint arthroplasty, thromboembolism, prophylaxis, AAOS guidelines. © 2008 Elsevier Inc. All rights reserved.
bitic syndrome, and pulmonary embolism (PE), a modality that does all these things probably does not exist; and attempts to do so may result in unintended complications. A few years ago, the American College of Chest Physicians (ACCP), in their attempt to assist the orthopedic community in preventing venous thromboembolic events after joint arthroplasty, issued guidelines [1]. These guidelines were developed based on evaluation of the available literature using prevention of distal DVT as the end point in determining the efficacy of various agents. Distal DVT was chosen as the end point because most randomized studies, particularly those sponsored by the pharmaceutical industry, were compelled to use an end point with a relatively common incidence. Choosing PE with its very low incidence as an end point for efficacy would require many thousands of subjects in such studies. The ACCP guidelines were received with little enthusiasm by the orthopedic community [2], who declared that the ACCP had chosen an “inappropriate” end point. Distal DVT is a relatively common
The debate as to what constitutes the most effective strategy to prevent venous thromboembolism (VTE) after total joint arthroplasty continues. Despite all efforts, it is unlikely that a “single” strategy can be developed. There is a multitude of reasons for failing to find the most effective agent or modality, most importantly those related to the uncertainty about which particular thromboembolic event the orthopedic community is attempting to prevent. Although it is most desirable to prevent every thromboembolic event such as distal and proximal deep venous thrombosis (DVT), postphle-
From the Rothman Institute of Orthopedics at Thomas Jefferson University, Philadelphia, PA. Submitted May 29, 2008; accepted June 20, 2008. No benefits or funds were received in support of the study. Reprint requests: Javad Parvizi, MD, FRCS, Department of Orthopaedic Surgery, Thomas Jefferson University Hospital, Rothman Institute, 925 Chestnut St, 5th Floor, Philadelphia, PA 19107. © 2008 Elsevier Inc. All rights reserved. 0883-5403/08/2307-0002$34.00/0 doi:10.1016/j.arth.2008.06.028
2
Thrombosis After Joint Arthroplasty Parvizi et al
event after joint arthroplasty; and prevention of such events has not been proven to prevent the clinically more important event, PE. The orthopedic community also remains concerned that implementation of protocols aiming to prevent distal DVT will lead to increased complications such as bleeding, reoperation, and infection, which could all lead to complications as serious as VTE itself. In addition, there were concerns that these guidelines would be misconstrued as the “standard of care” for orthopedic patients and that any deviation from the guidelines would have legal implications.
Chemoprophylaxis Increases the Risk of Bleeding, Blood Transfusion, and Periprosthetic Infection There is substantial evidence in the literature that administration of anticoagulation chemoprophylaxis places patients at risk of bleeding after total joint arthroplasty. The incidence of major bleeding appears to approximate 0.5% in patients without chemoprophylaxis [3] and variably rises to as high as 5% in patients given chemoprophylactic agents [4-8]. The occurrence of major bleeding complications after an elective total joint arthroplasty is regarded by most surgeons as unacceptable because of the potential for the subsequent occurrence of more important complications such as infection, wound healing problems, functional disability, and loosening that have a high probability of compromising the surgical outcome. The ACCP guidelines do not recognize agents such as aspirin, with minimal risk for bleeding, and advocate low–molecular weight heparinoids (LMWHs) and warfarin with a goal to keep the international normalized ratio (INR) higher than 2. The concern of the orthopedic community that implementation of ACCP guidelines may lead to higher incidence of postoperative bleeding was demonstrated in a recent study [9]. Compliance with the ACCP-1A protocol by administering a 10-day course of enoxaparin sodium at 30 mg twice daily after total hip arthroplasty led to an increase in the incidence of major complications that included readmission to hospital (4.7%), reoperation for wound drainage and bleeding (3.4%), and prolonged hospitalization because of wound drainage (5.1%). Return to the operating room for wound complications occurred 3 times more frequently with the use of enoxaparin than the previous anticoagulation protocol using warfarin. Despite the use of enoxaparin, symptomatic DVTs still occurred in 3.8% of patients; and nonfatal pulmonary emboli were diagnosed in 1.3% of the patients [9].
3
Another study on 1035 patients, evaluating the predictors for transfusion after total hip arthroplasty, demonstrated that administration of low– molecular weight heparins increased the likelihood of the need for transfusion (P b .0001, odds ratio = 2.76) [10]. In a case-control study of 3500 patients, patients with higher INR were more likely to develop prosthetic joint infections [11]. A recent study by Dorr et al [12] showed that the use of LMWH/warfarin for VTE prophylaxis in high-risk patients was associated with a significantly higher incidence of hematoma formation compared with the use of antiplatelet agents combined with mechanical prophylaxis [12].
Chemoprophylaxis Does Not Reduce Mortality It appears that despite administration of various chemoprophylactic agents, the orthopedic community has made little impact on the incidence of fatal and nonfatal pulmonary embolus over the last 10 to 15 years [13,14]. An interesting recent study evaluated the available literature and found that the incidence of all-cause mortality was in fact higher after administration of chemoprophylaxis compared with mechanical compression devices and aspirin [15]. Although the finding of this study may at first sight appear counterintuitive, it can be comprehended in the context of increased complications that may occur after administration of chemoprophylaxis, some of which can be fatal. It is also interesting to note that the evaluation of the literature by the American Academy of Orthopaedic Surgeons (AAOS) workgroup revealed that there was no difference in efficacy among different agents with regard to prevention of PE; and hence, these guidelines recognize mechanical prophylaxis and aspirin as a modality of choice for prevention of VTE. However, in the clinical scenario where the risk of VTE clearly outweighs the risk of major bleeding complications after operation, the AAOS guidelines are in agreement with the AACP guidelines advocating administration of chemoprophylaxis other than aspirin.
The AAOS Guidelines The AAOS convened a group of experts and representatives from various organizations including the Hip Society, the Knee Society, the American Association of Hip and Knee Surgeons, and the Orthopedic Trauma Association and experts from the Evidence Based Division at
4 The Journal of Arthroplasty Vol. 23 No. 7 Suppl. 1 October 2008 Tufts University to evaluate the available data to determine the efficacy of various agents in preventing what is believed to be more important for orthopedic surgeons, namely, fatal and nonfatal pulmonary emboli [16]. Although both the ACCP and the AAOS guidelines were devised with the good intention of minimizing the impact of VTE in patients undergoing total joint arthroplasty, because of using different “end points,” the guidelines differ in substance. Besides choosing fatal and nonfatal pulmonary emboli as the end points for measuring efficacy, the AAOS workgroup also attempted to evaluate the risk of bleeding, reoperation, and hospital readmission with the use of various agents. As the latter complications are not uncommon after administration of chemoprophylaxis, the AAOS workgroup also advocated that risk stratification should be implemented when, for any given individual, the risk of bleeding should be weighed against the risk for VTE. An important point to recall, however, is that because of the very low incidence of pulmonary emboli, a proper study evaluating the difference in efficacy between agents would be impractical. The latter constitutes the reason why the recommendations of the AAOS workgroup are based on nonrandomized and historical studies. These guidelines were created as an educational tool to guide the qualified orthopedic surgeons through a series of diagnostic and treatment decisions in an effort to improve the quality and efficiency of care. Hence, these guidelines take a “holistic” approach to VTE prophylaxis, providing guidance with regard to preoperative, intraoperative, and postoperative care. Preoperative Care • All patients should be assessed preoperatively for risk of DVT after surgery (Table 1). Patients without previous history of thromboembolic disorders, not currently being treated with anticoagulants, and able to mobilize easily are generally not at increased risk of DVT/PE. • All patients should be assessed preoperatively for risk of major bleeding in response to DVT prophylaxis (Table 1, available online at www. arthroplastyjournal.org). • Patients at increased risk for PE and increased risk for major bleeding should be considered for vena cava filter placement. In addition, patients at high risk for PE who have contraindications to chemoprophylaxis should also be considered for vena cava filter.
Intraoperative Care • Unless contraindicated, all patients should have intraoperative and/or immediate postoperative mechanical prophylaxis. • Patients at increased risk of thromboembolism should preferably receive regional anesthesia (spinal/epidural) and operative time of less than 2 hours.
Postoperative/Inpatient Care • All patients should be mobilized as soon as feasible to the full extent of medical safety and comfort postoperatively. A plan for pain management that allows control for the patient to be out of bed and subsequently ambulate should be in place before surgery. All patients should be out of bed to a sitting chair several times a day for several hours at a time to encourage deep breathing and avoid recumbency. Practices should be in place to guarantee that appropriate physical therapy, ambulatory assistance, and support are provided by the first postoperative day. • Patients who are treated with epidural catheters postoperatively should be out of bed to chair as above. Standing and ambulation should begin for these patients when they are physically capable. • Patients who have an occurrence or event that restricts mobility should be considered to be at increased risk for DVT. Following are examples: • Infection (eg, urinary tract infection, pneumonia, severe wound infection) • Electrocardiogram changes that restrict ambulation • Postoperative ileus • Active exercises should be started within the confines of medical safety and pain tolerance. At a minimum, patients should be taught to actively dorsiflex and plantarflex the ankle and toes. This exercise should be performed in sets of 10 to 20 every half hour when the patient is awake. • Mechanical prophylaxis should remain in place when the patient is out of bed and be discontinued only for ambulation. Mechanical agents have no bleeding risk, but it has not been demonstrated that they reduce the incidence of PE. Therefore, they remain an adjunct in the armamentarium for prophylaxis in routine total joint surgery. In a normal, rapidly mobilized patient, they may be
Thrombosis After Joint Arthroplasty Parvizi et al
considered for use in bed in the hospital after surgery. There are no data on the extended use of mechanical agents. • Routine screening for thromboembolism postoperatively in asymptomatic patients is not recommended. There neither is a sufficiently sensitive noninvasive screening tool nor is there a clear definition of the period of risk for VTE as to make routine screening reliably predictive or cost-effective in preventing PE.
6.
7.
8.
Chemoprophylaxis The AAOS guidelines stratify patients based on their risk for bleeding and risk for developing VTE. Therefore, the type of prophylaxis used for each group differs based on these factors (Table 2, available at www.arthroplastyjournal.org). The guidelines provided dosage and timing for the chemoprophylactic agents also (Table 3, available at www.arthroplastyjournal.org).
References 1. Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 Suppl):338S. 2. Callaghan JJ, Dorr LD, Engh GA, et al. Prophylaxis for thromboembolic disease: recommendations from the American College of Chest Physicians—are they appropriate for orthopaedic surgery? J Arthroplasty 2005;20:273. 3. Coventry MB, Nolan DR, Beckenbaugh RD. “Delayed” prophylactic anticoagulation: a study of results and complications in 2,012 total hip arthroplasties. J Bone Joint Surg Am 1973;55:1487. 4. Enyart JJ, Jones RJ. Low-dose warfarin for prevention of symptomatic thromboembolism after orthopedic surgery. Ann Pharmacother 2005;39:1002. 5. Fitzgerald Jr RH, Spiro TE, Trowbridge AA, et al. Prevention of venous thromboembolic disease following primary total knee arthroplasty. A randomized, multicenter, open-label, parallel-group comparison of
9.
10.
11.
12.
13.
14.
15.
16.
5
enoxaparin and warfarin. J Bone Joint Surg Am 2001;83-A:900. Brookenthal KR, Freedman KB, Lotke PA, et al. A meta-analysis of thromboembolic prophylaxis in total knee arthroplasty. J Arthroplasty 2001;16:293. Turpie AG, Bauer KA, Eriksson BI, et al. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med 2002;162:1833. Freedman KB, Brookenthal KR, Fitzgerald Jr RH, et al. A meta-analysis of thromboembolic prophylaxis following elective total hip arthroplasty. J Bone Joint Surg Am 2000;82-A:929. Burnett RS, Clohisy JC, Wright RW, et al. Failure of the American College of Chest Physicians–1A protocol for enoxaparin in clinical outcomes for thromboembolic prophylaxis. J Arthroplasty 2007;22:317. Walsh M, Preston C, Bong M, et al. Relative risk factors for requirement of blood transfusion after total hip arthroplasty. J Arthroplasty 2007;22:1162. Parvizi J, Ghanem E, Joshi A, et al. Does “excessive” anticoagulation predispose to periprosthetic infection? J Arthroplasty 2007;22(Suppl 2):24. Dorr LD, Gendelman V, Maheshwari AV, et al. Multimodal thromboprophylaxis for total hip and knee arthroplasty based on risk assessment. J Bone Joint Surg Am 2007;89:2648. Lie SA, Engesaeter LB, Havelin LI, et al. Early postoperative mortality after 67,548 total hip replacements: causes of death and thromboprophylaxis in 68 hospitals in Norway from 1987 to 1999. Acta Orthop Scand 2002;73:392. Howie C, Hughes H, Watts AC. Venous thromboembolism associated with hip and knee replacement over a ten-year period: a population-based study. J Bone Joint Surg Br 2005;87:1675. Sharrock NE, Gonzalez DV, Go G, et al. Potent anticoagulants are associated with a higher all-cause mortality rate after hip and knee arthroplasty. Clin Orthop Relat Res 2008;466:714. American Academy of Orthopaedic Surgeons clinical guideline on prevention of symptomatic pulmonary embolism in patients undergoing total hip or knee arthroplasty. Available at http://www.aaos.org/ Research/guidelines/guide.asp, 2007.
Thrombosis After Joint Arthroplasty Parvizi et al
Appendix A. Supplementary Tables Table 1. Conditions That Place Patients at Increased Risk of PE and/or Major Bleeding (Compared With Other Patients Having THA) Increased Risk of PE Preoperative conditions Previous documented history of PE Previous documented history of other thromboembolic events Maintenance treatment with anticoagulants Limitations to mobility that would impair early adequate mobilization postsurgery Known hypercoagulable states (malignancy, estrogen use, protein C and S deficiency, antiphospholipid antibodies, antithrombin deficiency, factor V Leiden, acquired or congenital thrombophilias, prothrombin mutation 20210A, hyperhomocystinemia) Documented family history of PE Obesity, smoking, venous stasis, IDDM, concomitant fracture Hormone replacement therapy or continuing on oral contraceptive (other than low-dose progesterone only) Perioperative events Any event that limits mobilization, including but not limited to Cardiac events Infections Severe pain Ileus
Increased Risk of Major Bleeding Preoperative conditions Known bleeding disorder History of documented bleeding on chemoprophylaxis agents History of documented major gastrointestinal bleeding History of documented hemorrhagic stroke History of other documented major bleeding event
5.e1
Table 2. Selection of the Most Appropriate Chemotherapeutic Prophylaxis Based on Patients' Risk of Bleeding and Risk of Developing VTE Bleeding
VTE
Standard risk
High risk
Standard Risk
High Risk
a. Aspirin b. LMWHs c. Synthetic pentasaccharides d. Warfarin a. LMWHs b. Synthetic pentasaccharides c. Warfarin
a. Aspirin b. Warfarin c. None a. Aspirin b. Warfarin c. None
Patients should receive one of the chemoprophylactic agents evaluated in this guideline.
Table 3. The Dosage and Timing of Chemoprophylactic Agents That Should Be Considered Drug
Dose
Start Time
Aspirin
325 ‡ 2×/d
LMWH Fondaparinux Warfarin
Per package Per package INR ≤2.0
Day of surgery 12-24 h postop § 12-24 h postop § Night before/after
Combinations
Perioperative events Revision THA/TKA Major surgical site bleeding Other major bleeding episode
In general, the definitions of a major bleed include lifethreatening, intraocular, or intracerebral bleed or one requiring more than a specified number of transfusions. IDDM indicates insulin-dependent diabetes mellitus; THA, total hip arthroplasty; TKA, total knee arthroplasty.
Duration of Treatment * 6 wk 7-12 d † 7-12 d † 3-6 wk Unclear (no data)
* The duration for the administration of chemoprophylactic agents has not been clearly established. The older literature notes that most postoperative PE occurred within the first 6 weeks. Therefore, many regimens were established to encompass that experience. † There are some data, with the heparin-like drugs, which show that it is not necessary to prolong the administration beyond the first 8 to 12 days. These recommendations reflect those practices. ‡ Can be adjusted down to 81 mg once a day for gastrointestinal symptoms. § Or after indwelling epidural catheter is removed.
Deep Venous Thrombosis Prophylaxis for Total Joint Arthroplasty: American Academy of Orthopaedic Surgeons Guidelines Javad Parvizi, MD, FRCS, Khalid Azzam, MD, and Richard H. Rothman, MD, PhD
Abstract: The orthopedic community continues to face a challenge with regard to the prevention of thromboembolism after total joint arthroplasty. The first and foremost issue facing surgeons is how to select the best agent or modality that is effective in preventing the untoward consequences of thromboembolism without causing other complications that can have dire consequences. Other challenges include the uncertainty regarding the dose and duration of various agents, the value of mechanical prophylaxis alone, and the exact end points that should be used to measure the efficacy of prophylaxis. This article discusses some of the recent developments in prevention and management of thromboembolism after total joint arthroplasty, in particular highlighting the guidelines that were developed by American Academy of Orthopedic Surgeons. Key words: total joint arthroplasty, thromboembolism, prophylaxis, AAOS guidelines. © 2008 Elsevier Inc. All rights reserved.
bitic syndrome, and pulmonary embolism (PE), a modality that does all these things probably does not exist; and attempts to do so may result in unintended complications. A few years ago, the American College of Chest Physicians (ACCP), in their attempt to assist the orthopedic community in preventing venous thromboembolic events after joint arthroplasty, issued guidelines [1]. These guidelines were developed based on evaluation of the available literature using prevention of distal DVT as the end point in determining the efficacy of various agents. Distal DVT was chosen as the end point because most randomized studies, particularly those sponsored by the pharmaceutical industry, were compelled to use an end point with a relatively common incidence. Choosing PE with its very low incidence as an end point for efficacy would require many thousands of subjects in such studies. The ACCP guidelines were received with little enthusiasm by the orthopedic community [2], who declared that the ACCP had chosen an “inappropriate” end point. Distal DVT is a relatively common
The debate as to what constitutes the most effective strategy to prevent venous thromboembolism (VTE) after total joint arthroplasty continues. Despite all efforts, it is unlikely that a “single” strategy can be developed. There is a multitude of reasons for failing to find the most effective agent or modality, most importantly those related to the uncertainty about which particular thromboembolic event the orthopedic community is attempting to prevent. Although it is most desirable to prevent every thromboembolic event such as distal and proximal deep venous thrombosis (DVT), postphle-
From the Rothman Institute of Orthopedics at Thomas Jefferson University, Philadelphia, PA. Submitted May 29, 2008; accepted June 20, 2008. No benefits or funds were received in support of the study. Reprint requests: Javad Parvizi, MD, FRCS, Department of Orthopaedic Surgery, Thomas Jefferson University Hospital, Rothman Institute, 925 Chestnut St, 5th Floor, Philadelphia, PA 19107. © 2008 Elsevier Inc. All rights reserved. 0883-5403/08/2307-0002$34.00/0 doi:10.1016/j.arth.2008.06.028
2
Thrombosis After Joint Arthroplasty Parvizi et al
event after joint arthroplasty; and prevention of such events has not been proven to prevent the clinically more important event, PE. The orthopedic community also remains concerned that implementation of protocols aiming to prevent distal DVT will lead to increased complications such as bleeding, reoperation, and infection, which could all lead to complications as serious as VTE itself. In addition, there were concerns that these guidelines would be misconstrued as the “standard of care” for orthopedic patients and that any deviation from the guidelines would have legal implications.
Chemoprophylaxis Increases the Risk of Bleeding, Blood Transfusion, and Periprosthetic Infection There is substantial evidence in the literature that administration of anticoagulation chemoprophylaxis places patients at risk of bleeding after total joint arthroplasty. The incidence of major bleeding appears to approximate 0.5% in patients without chemoprophylaxis [3] and variably rises to as high as 5% in patients given chemoprophylactic agents [4-8]. The occurrence of major bleeding complications after an elective total joint arthroplasty is regarded by most surgeons as unacceptable because of the potential for the subsequent occurrence of more important complications such as infection, wound healing problems, functional disability, and loosening that have a high probability of compromising the surgical outcome. The ACCP guidelines do not recognize agents such as aspirin, with minimal risk for bleeding, and advocate low–molecular weight heparinoids (LMWHs) and warfarin with a goal to keep the international normalized ratio (INR) higher than 2. The concern of the orthopedic community that implementation of ACCP guidelines may lead to higher incidence of postoperative bleeding was demonstrated in a recent study [9]. Compliance with the ACCP-1A protocol by administering a 10-day course of enoxaparin sodium at 30 mg twice daily after total hip arthroplasty led to an increase in the incidence of major complications that included readmission to hospital (4.7%), reoperation for wound drainage and bleeding (3.4%), and prolonged hospitalization because of wound drainage (5.1%). Return to the operating room for wound complications occurred 3 times more frequently with the use of enoxaparin than the previous anticoagulation protocol using warfarin. Despite the use of enoxaparin, symptomatic DVTs still occurred in 3.8% of patients; and nonfatal pulmonary emboli were diagnosed in 1.3% of the patients [9].
3
Another study on 1035 patients, evaluating the predictors for transfusion after total hip arthroplasty, demonstrated that administration of low– molecular weight heparins increased the likelihood of the need for transfusion (P b .0001, odds ratio = 2.76) [10]. In a case-control study of 3500 patients, patients with higher INR were more likely to develop prosthetic joint infections [11]. A recent study by Dorr et al [12] showed that the use of LMWH/warfarin for VTE prophylaxis in high-risk patients was associated with a significantly higher incidence of hematoma formation compared with the use of antiplatelet agents combined with mechanical prophylaxis [12].
Chemoprophylaxis Does Not Reduce Mortality It appears that despite administration of various chemoprophylactic agents, the orthopedic community has made little impact on the incidence of fatal and nonfatal pulmonary embolus over the last 10 to 15 years [13,14]. An interesting recent study evaluated the available literature and found that the incidence of all-cause mortality was in fact higher after administration of chemoprophylaxis compared with mechanical compression devices and aspirin [15]. Although the finding of this study may at first sight appear counterintuitive, it can be comprehended in the context of increased complications that may occur after administration of chemoprophylaxis, some of which can be fatal. It is also interesting to note that the evaluation of the literature by the American Academy of Orthopaedic Surgeons (AAOS) workgroup revealed that there was no difference in efficacy among different agents with regard to prevention of PE; and hence, these guidelines recognize mechanical prophylaxis and aspirin as a modality of choice for prevention of VTE. However, in the clinical scenario where the risk of VTE clearly outweighs the risk of major bleeding complications after operation, the AAOS guidelines are in agreement with the AACP guidelines advocating administration of chemoprophylaxis other than aspirin.
The AAOS Guidelines The AAOS convened a group of experts and representatives from various organizations including the Hip Society, the Knee Society, the American Association of Hip and Knee Surgeons, and the Orthopedic Trauma Association and experts from the Evidence Based Division at
4 The Journal of Arthroplasty Vol. 23 No. 7 Suppl. 1 October 2008 Tufts University to evaluate the available data to determine the efficacy of various agents in preventing what is believed to be more important for orthopedic surgeons, namely, fatal and nonfatal pulmonary emboli [16]. Although both the ACCP and the AAOS guidelines were devised with the good intention of minimizing the impact of VTE in patients undergoing total joint arthroplasty, because of using different “end points,” the guidelines differ in substance. Besides choosing fatal and nonfatal pulmonary emboli as the end points for measuring efficacy, the AAOS workgroup also attempted to evaluate the risk of bleeding, reoperation, and hospital readmission with the use of various agents. As the latter complications are not uncommon after administration of chemoprophylaxis, the AAOS workgroup also advocated that risk stratification should be implemented when, for any given individual, the risk of bleeding should be weighed against the risk for VTE. An important point to recall, however, is that because of the very low incidence of pulmonary emboli, a proper study evaluating the difference in efficacy between agents would be impractical. The latter constitutes the reason why the recommendations of the AAOS workgroup are based on nonrandomized and historical studies. These guidelines were created as an educational tool to guide the qualified orthopedic surgeons through a series of diagnostic and treatment decisions in an effort to improve the quality and efficiency of care. Hence, these guidelines take a “holistic” approach to VTE prophylaxis, providing guidance with regard to preoperative, intraoperative, and postoperative care. Preoperative Care • All patients should be assessed preoperatively for risk of DVT after surgery (Table 1). Patients without previous history of thromboembolic disorders, not currently being treated with anticoagulants, and able to mobilize easily are generally not at increased risk of DVT/PE. • All patients should be assessed preoperatively for risk of major bleeding in response to DVT prophylaxis (Table 1, available online at www. arthroplastyjournal.org). • Patients at increased risk for PE and increased risk for major bleeding should be considered for vena cava filter placement. In addition, patients at high risk for PE who have contraindications to chemoprophylaxis should also be considered for vena cava filter.
Intraoperative Care • Unless contraindicated, all patients should have intraoperative and/or immediate postoperative mechanical prophylaxis. • Patients at increased risk of thromboembolism should preferably receive regional anesthesia (spinal/epidural) and operative time of less than 2 hours.
Postoperative/Inpatient Care • All patients should be mobilized as soon as feasible to the full extent of medical safety and comfort postoperatively. A plan for pain management that allows control for the patient to be out of bed and subsequently ambulate should be in place before surgery. All patients should be out of bed to a sitting chair several times a day for several hours at a time to encourage deep breathing and avoid recumbency. Practices should be in place to guarantee that appropriate physical therapy, ambulatory assistance, and support are provided by the first postoperative day. • Patients who are treated with epidural catheters postoperatively should be out of bed to chair as above. Standing and ambulation should begin for these patients when they are physically capable. • Patients who have an occurrence or event that restricts mobility should be considered to be at increased risk for DVT. Following are examples: • Infection (eg, urinary tract infection, pneumonia, severe wound infection) • Electrocardiogram changes that restrict ambulation • Postoperative ileus • Active exercises should be started within the confines of medical safety and pain tolerance. At a minimum, patients should be taught to actively dorsiflex and plantarflex the ankle and toes. This exercise should be performed in sets of 10 to 20 every half hour when the patient is awake. • Mechanical prophylaxis should remain in place when the patient is out of bed and be discontinued only for ambulation. Mechanical agents have no bleeding risk, but it has not been demonstrated that they reduce the incidence of PE. Therefore, they remain an adjunct in the armamentarium for prophylaxis in routine total joint surgery. In a normal, rapidly mobilized patient, they may be
Thrombosis After Joint Arthroplasty Parvizi et al
considered for use in bed in the hospital after surgery. There are no data on the extended use of mechanical agents. • Routine screening for thromboembolism postoperatively in asymptomatic patients is not recommended. There neither is a sufficiently sensitive noninvasive screening tool nor is there a clear definition of the period of risk for VTE as to make routine screening reliably predictive or cost-effective in preventing PE.
6.
7.
8.
Chemoprophylaxis The AAOS guidelines stratify patients based on their risk for bleeding and risk for developing VTE. Therefore, the type of prophylaxis used for each group differs based on these factors (Table 2, available at www.arthroplastyjournal.org). The guidelines provided dosage and timing for the chemoprophylactic agents also (Table 3, available at www.arthroplastyjournal.org).
References 1. Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 Suppl):338S. 2. Callaghan JJ, Dorr LD, Engh GA, et al. Prophylaxis for thromboembolic disease: recommendations from the American College of Chest Physicians—are they appropriate for orthopaedic surgery? J Arthroplasty 2005;20:273. 3. Coventry MB, Nolan DR, Beckenbaugh RD. “Delayed” prophylactic anticoagulation: a study of results and complications in 2,012 total hip arthroplasties. J Bone Joint Surg Am 1973;55:1487. 4. Enyart JJ, Jones RJ. Low-dose warfarin for prevention of symptomatic thromboembolism after orthopedic surgery. Ann Pharmacother 2005;39:1002. 5. Fitzgerald Jr RH, Spiro TE, Trowbridge AA, et al. Prevention of venous thromboembolic disease following primary total knee arthroplasty. A randomized, multicenter, open-label, parallel-group comparison of
9.
10.
11.
12.
13.
14.
15.
16.
5
enoxaparin and warfarin. J Bone Joint Surg Am 2001;83-A:900. Brookenthal KR, Freedman KB, Lotke PA, et al. A meta-analysis of thromboembolic prophylaxis in total knee arthroplasty. J Arthroplasty 2001;16:293. Turpie AG, Bauer KA, Eriksson BI, et al. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med 2002;162:1833. Freedman KB, Brookenthal KR, Fitzgerald Jr RH, et al. A meta-analysis of thromboembolic prophylaxis following elective total hip arthroplasty. J Bone Joint Surg Am 2000;82-A:929. Burnett RS, Clohisy JC, Wright RW, et al. Failure of the American College of Chest Physicians–1A protocol for enoxaparin in clinical outcomes for thromboembolic prophylaxis. J Arthroplasty 2007;22:317. Walsh M, Preston C, Bong M, et al. Relative risk factors for requirement of blood transfusion after total hip arthroplasty. J Arthroplasty 2007;22:1162. Parvizi J, Ghanem E, Joshi A, et al. Does “excessive” anticoagulation predispose to periprosthetic infection? J Arthroplasty 2007;22(Suppl 2):24. Dorr LD, Gendelman V, Maheshwari AV, et al. Multimodal thromboprophylaxis for total hip and knee arthroplasty based on risk assessment. J Bone Joint Surg Am 2007;89:2648. Lie SA, Engesaeter LB, Havelin LI, et al. Early postoperative mortality after 67,548 total hip replacements: causes of death and thromboprophylaxis in 68 hospitals in Norway from 1987 to 1999. Acta Orthop Scand 2002;73:392. Howie C, Hughes H, Watts AC. Venous thromboembolism associated with hip and knee replacement over a ten-year period: a population-based study. J Bone Joint Surg Br 2005;87:1675. Sharrock NE, Gonzalez DV, Go G, et al. Potent anticoagulants are associated with a higher all-cause mortality rate after hip and knee arthroplasty. Clin Orthop Relat Res 2008;466:714. American Academy of Orthopaedic Surgeons clinical guideline on prevention of symptomatic pulmonary embolism in patients undergoing total hip or knee arthroplasty. Available at http://www.aaos.org/ Research/guidelines/guide.asp, 2007.
Thrombosis After Joint Arthroplasty Parvizi et al
Appendix A. Supplementary Tables Table 1. Conditions That Place Patients at Increased Risk of PE and/or Major Bleeding (Compared With Other Patients Having THA) Increased Risk of PE Preoperative conditions Previous documented history of PE Previous documented history of other thromboembolic events Maintenance treatment with anticoagulants Limitations to mobility that would impair early adequate mobilization postsurgery Known hypercoagulable states (malignancy, estrogen use, protein C and S deficiency, antiphospholipid antibodies, antithrombin deficiency, factor V Leiden, acquired or congenital thrombophilias, prothrombin mutation 20210A, hyperhomocystinemia) Documented family history of PE Obesity, smoking, venous stasis, IDDM, concomitant fracture Hormone replacement therapy or continuing on oral contraceptive (other than low-dose progesterone only) Perioperative events Any event that limits mobilization, including but not limited to Cardiac events Infections Severe pain Ileus
Increased Risk of Major Bleeding Preoperative conditions Known bleeding disorder History of documented bleeding on chemoprophylaxis agents History of documented major gastrointestinal bleeding History of documented hemorrhagic stroke History of other documented major bleeding event
5.e1
Table 2. Selection of the Most Appropriate Chemotherapeutic Prophylaxis Based on Patients' Risk of Bleeding and Risk of Developing VTE Bleeding
VTE
Standard risk
High risk
Standard Risk
High Risk
a. Aspirin b. LMWHs c. Synthetic pentasaccharides d. Warfarin a. LMWHs b. Synthetic pentasaccharides c. Warfarin
a. Aspirin b. Warfarin c. None a. Aspirin b. Warfarin c. None
Patients should receive one of the chemoprophylactic agents evaluated in this guideline.
Table 3. The Dosage and Timing of Chemoprophylactic Agents That Should Be Considered Drug
Dose
Start Time
Aspirin
325 ‡ 2×/d
LMWH Fondaparinux Warfarin
Per package Per package INR ≤2.0
Day of surgery 12-24 h postop § 12-24 h postop § Night before/after
Combinations
Perioperative events Revision THA/TKA Major surgical site bleeding Other major bleeding episode
In general, the definitions of a major bleed include lifethreatening, intraocular, or intracerebral bleed or one requiring more than a specified number of transfusions. IDDM indicates insulin-dependent diabetes mellitus; THA, total hip arthroplasty; TKA, total knee arthroplasty.
Duration of Treatment * 6 wk 7-12 d † 7-12 d † 3-6 wk Unclear (no data)
* The duration for the administration of chemoprophylactic agents has not been clearly established. The older literature notes that most postoperative PE occurred within the first 6 weeks. Therefore, many regimens were established to encompass that experience. † There are some data, with the heparin-like drugs, which show that it is not necessary to prolong the administration beyond the first 8 to 12 days. These recommendations reflect those practices. ‡ Can be adjusted down to 81 mg once a day for gastrointestinal symptoms. § Or after indwelling epidural catheter is removed.