Guidelines help clinicians identify safe DVT prophylaxis strategies, suggest research directions

Until recently, orthopedic surgeons lacked specialty-specific recommendations for preventing venous thromboembolism. They agreed on the need for clear guidelines for deep vein thrombosis and pulmonary embolism prophylaxis that addressed the requirements of their patients undergoing surgery for total joint replacement, traumatic injuries or spine problems.

However, the consensus in the orthopedic community was the recommendations available through just a few years ago, mostly from the American College of Chest Physicians, were suboptimal and possibly even dangerous because they did not accurately consider the risk of bleeding in orthopedic surgical patients.

In 2007, the American Academy of Orthopaedic Surgeons (AAOS) approved a clinical guideline on prevention of symptomatic pulmonary embolism (PE) in patients undergoing total hip or knee arthroplasty to improve patient care in these areas. This evidence-based guideline involved a systematic review of the published orthopedic literature on adults undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). Importantly, the AAOS guideline addressed the fact THA and TKA patients have different risks of deep vein thrombosis (DVT) and PE than other surgical patients. It also gave more consideration to the risk associated with bleeding in orthopedic patients, which also increases the risk of wound problems and in turn can threaten underlying orthopedic hardware and contribute to poor outcomes.

The AAOS guideline, which delved into the helpful yet controversial area of risk stratifying patients for these problems, excluded traumatic cases. It also left orthopedic spine surgeons wanting venous thromboembolism (VTE) information suited to a patient population that tended to develop bleedings and hematomas when treated with VTE prophylaxis according to the American College of Chest Physicians’ (ACCP) guidelines.

A new direction

The AAOS clinical guideline on preventing PE in THA or TKA patients offers practical, patient-specific advice that total joint replacement (TJR) surgeons can readily apply, according to Robert L. Barrack, MD, chief of service for the Department of Orthopaedic Surgery at Washington University in St. Louis.

Robert L. Barrack, MD, chief of service for the Department of Orthopaedic Surgery at Washington University, St. Louis, said that using foot pumps and aspirin is acceptable practice for DVT prophylaxis in many total joint reconstruction cases. Image: Strauss Peyton

“I think orthopedic surgeons are in agreement with them, in general,” he said. “What is needed in the future is more high-quality data. That is sort of a recurring theme if you read the academy guidelines. There is disappointment in the level of data, with few level 1 or even level 2 studies included.”

The work group that compiled the AAOS guideline analyzed available evidence for prevention of symptomatic PE. Instead of using an endpoint of venographically detected clots, as did the ACCP literature review, the AAOS group used symptomatic PE as its endpoint. Barrack and others found that method to be more realistic and appropriate for TJR patients whose symptomatic thromboembolic disease risk may be lower.

Barrack cited the fairly rigorous methodology based on principles of evidence-based medicine among the advantages of the ACCP guidelines. “But in reality, many of us felt the conclusions they came to were not in the best interest of our patients,” said Barrack, who called the chest physicians’ 1A protocols “aggressive” by his standards.

William J. Maloney III, MD, Elsbach-Richards professor and chair of orthopaedic surgery, Department of Orthopaedic Surgery, Stanford University School of Medicine, said, “Many surgeons feel the chest physicians’ guidelines, albeit supported by randomized prospective trials, use an endpoint that we are not really concerned about, which puts some patients at an unnecessary risk of bleeding.”

AAOS guideline

According to statistics from AAOS, without mechanical and pharmacologic prophylaxis TJR patients have a 40% to 60% risk of developing asymptomatic DVT, a 15% to 25% risk of developing proximal DVT and a 0.5% to 2% risk for fatal PE.

The AAOS guideline encourages assessing TJR patients’ risk of PE and postoperative bleeding, mobilizing them when possible and using mechanical prophylaxis. Based on level of risk, preferred chemoprophylaxis regimens include aspirin, low molecular-weight heparin (LMWH), synthetic pentasaccharides or warfarin, with international normalized ratio (INR) targets that differ from the ACCP guidelines.

However, orthopedists continue to recognize the importance of making VTE management decisions on a case-by-case basis using sound clinical judgment and having a clear rationale why each strategy was selected. In fact, as stated in the AAOS guideline, “Patient care and treatment should always be based on a clinician’s independent medical judgment, given the individual patient’s clinical circumstances.”

When an inordinate percentage of patients in their prospective study of an ACCP 1A protocol developed persistent wound draining, bleeding and hematomas, Barrack and colleagues halted the study early. Other investigators encountered similar problems following the protocol. The latest version of ACCP guidelines are even more liberal concerning aggressive anticoagulation for extended duration of use, Barrack added.

“The academy advocates that patients be stratified based on their risk for bleeding and risk for DVT and PE. The chest physicians basically do not stratify,” said Barrack, who uses in low- to medium-risk patients such AAOS-supported modalities such as mobile foot pumps with aspirin or Coumadin (warfarin sodium, Bristol-Myers Squibb), particularly lower-dose Coumadin, with a target INR of 2.0.

“The orthopedic surgeons are not overly concerned with asymptomatic clots as an endpoint because we do not see long-term problems with patients who have asymptomatic clots.” — William J. Maloney III, MD

Clinical judgment

“Our patients who do not have any risk factors that we think are clinically important do not even get Coumadin — they just get foot pumps and aspirin,” Barrack said, noting that this is a departure from the chest physicians’ definition of all TJR patients being high-risk.

Barrack and his TJR colleagues at Washington University are proponents of using foot pumps and are prospectively studying the use of a new, portable mobile foot pump. Studies of such a device demonstrated that they were worn 18 to 20 hours daily and showed equivalent efficacy to 10 days of Lovenox (enoxaparin sodium injection, Sanofi Aventis), but with a lower complication rate, said Barrack, who is concerned about overuse of aggressive drugs in patients at low-risk of clotting complications.

Up to 30% of patients can present with small clots of no clinical significance, particularly below the knee, yet it is fairly unclear what is indicated for them, particularly if they are not symptomatic, he said.

“The question is whether lowering the incidence of DVT from 30% to 15% also lowers the risk of clinically significant events, like PE. It is possible that lowering those numbers does not necessarily help your patients, but may generate data that are used to support the liberal use of expensive drugs that may carry more risk than benefit for patients.”

Balancing risks

According to Maloney, “From the orthopedic surgeon perspective, many felt the ACCP guidelines were only looking at half the picture. Really what we are trying to prevent are fatal PE. The orthopedic surgeons are not overly concerned with asymptomatic clots as an endpoint because we do not see long-term problems with patients who have asymptomatic clots. We want to balance the risk of clotting with the risk of bleeding.”

Among major problems TJR surgeons face is an inability to accurately stratify who is at risk of clotting or bleeding, an area Maloney and others plan to eventually study through a large multicenter trial tracking the effect these complications have on outcomes.

“There are some risk factors. There is no question about it,” he said. “This concept of balancing out risk of bleeding and risk of clotting and having that dictate your prophylactic regimen all makes perfect sense, but the data are not very good to do that.”

Maloney discussed obstacles faced by orthopedists who strictly adhere to the AAOS PE prophylaxis guideline, including being out of compliance with the Surgical Care Improvement Project (SCIP) regulations. Hospitals now request that if ACCP DVT prophylaxis guidelines, which are similar to the SCIP guidelines for VTE, are not followed physicians must state in the chart why they were not followed, otherwise they are out of compliance.

SCIP guidelines call for starting DVT prophylaxis with LMWH, fondaparinux or warfarin within 24 hours of elective THA surgery and for using LMWH, fondaparinux, warfarin or intermittent compression devices for elective TKA. Complying, or not, can affect Medicare payments and meeting critical performance measures, Maloney noted.

NASS gives input

As with TJR surgeons, trauma and spine surgeons have sought VTE prophylaxis guidance tailored to their patients’ unique issues and risks pertaining to DVT and PE.

“Each group of surgeons tries to do the same thing, risk stratify,” Maloney noted.

In 2009, the North American Spine Society (NASS) released an evidence-based clinical guideline for antithrombotic therapies in spine surgery. Prior to that, DVT prophylaxis strategies in spine cases were “haphazard” and “directionless,” said Christopher M. Bono, MD, of Brigham & Women’s Hospital in Boston.

Spine surgeons made individual decisions intraoperatively on a per-case basis, said Bono, who co-chaired the NASS Evidence-based Guideline Development Committee that developed NASS’ Antithrombotic Therapies in Spine Surgery guideline.

Bono told Orthopedics Today his colleagues felt the TJR guidelines were pushed on them and there was no agreement among spine specialists, so the NASS antithrombotic recommendations were needed. “AAOS recommendations are not relevant. The incidence of DVT and risks are different in our patients, particularly for epidural hematoma, which is a major complication in the spine. Extrapolating that literature is not really appropriate,” he said.

In fact, a study by Bono and colleagues confirmed considerable variability in anticoagulation practices among spine surgeons and reported more consistent approaches would be helpful.

Although still being debated, most spine surgeons welcomed the NASS guidance document, which supports mechanical prophylaxis for routine elective cases and chemical prophylaxis when mechanical methods are not feasible. Its suggested approach for high-risk trauma or neoplastic cases, or those with large deformities, involves some kind of chemoprophylaxis.

“The timing for continuing that is unclear,” explained Bono, who prescribes Lovenox and discontinues it once patients are ambulatory. His thromboprophylaxis practices include using compression devices on everyone at high risk for DVT, including cancer and trauma patients, and starting Lovenox at 48 hours postoperative. For spinal cord injuries, he extends chemoprophylaxis from 6 months to 1 year, but said even that practice is questionable.

Bono called for more research to identify those at increased risk of epidural hematoma, which he believes will reduce confusion among clinicians.

Trauma perspective

TJR and trauma surgeon Andrew H. Schmidt, MD, at Hennepin County Medical Center, in Minneapolis, finds the AAOS clinical guideline helpful for THA and TKA cases and patients with hip fractures. He notes that the ACCP VTE guidelines are focused solely on providing grade 1A recommendations, which limit the studies that are considered to those that mostly focus on chemoprophylactic agents for which level 1 evidence exists, such as using LMWH and similar strategies.

“The problem is that the risk of bleeding is significant in many of my patients and there are now studies coming from North America and the United Kingdom showing that bleeding complications are actually increased when overly aggressive chemoprophylaxis becomes mandated by policymakers,” he said. For example, a North American study by Novicoff and colleagues showed that with mandated LMWH use the risk of bleeding increased sevenfold, yet thromboembolism risk was unchanged.

“This highlights the problem that when you are really aggressive at preventing DVT with anticoagulation the price you pay is a higher rate of bleeding complications and infection,” Schmidt told Orthopedics Today. “There are other effective means of preventing DVT, like using mechanical devices and aspirin, which most clinicians feel is successful, but all the evidence is level 3 or 4 and is not given credence in the ACCP guidelines.”

Schmidt said, “From a trauma surgeon’s perspective, we are faced with a huge dilemma because we know that our patients are probably at even higher risk of DVT than total hip and knee patients,” noting the Geerts et al 1994 study, the first to highlight serious DVT prophylaxis issues in trauma patients, that included pelvic, spine and femur fractures.

VTE coverage in the trauma literature is limited because research is hampered by the inability to conduct studies with homogeneous groups large enough to detect a statistically significant difference in results.

“Those studies are just never going to be done,” Schmidt said.

But he applauded the Orthopaedic Trauma Association’s (OTA) efforts to date to educate members on the subject, and is hopeful that OTA research funds will go toward producing thromboprophylaxis evidence in trauma. “It is a huge area needing research,” Schmidt said.

Research is the future

Barrack noted the orthopedic community has welcomed the AAOS guideline, although some regard it as a little liberal concerning aspirin use. He urged orthopedists to read the AAOS document carefully. “Some sections seem to suggest that in some clinical scenarios it is OK to do nothing,” he said. “I think the consensus among most surgeons is that it would be pretty uncommon that you would not do anything for DVT prophylaxis.”

Barrack and colleagues in St. Louis and Hospital for Special Surgery in New York are conducting research on genetic factors as predictors of individual metabolism rates for Coumadin. They are also prospectively assessing low- vs. high-dose target INRs in terms of efficacy and complications when using Coumadin.

Another promising area of research — technology to help rapidly determine those at risk of clots or bleeds — may help orthopedists fine tune selection of prophylactic drug, dosing and duration for DVT chemoprophylaxis.

Maloney mentioned another next step toward effective preventing and treating potentially dangerous DVTs and PE: assessing the role of oral factor Xa inhibitors being studied in Europe. He said these drugs do not need monitoring and “definitely reduce venographically detected clots, but you do pay a price through bleeding. Again, the key is finding the right balance.” – by Susan M. Rapp

References:

• Burnett RS, Clohisy JC, Wright RW, et al. Failure of the American College of Chest Physicians-1A protocol for Lovenox in clinical outcomes for thromboembolic prophylaxis. J Arthroplasty. 2007;22:317-324.
• 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-400S.
• Johanson NA, Lachiewicz PF, Lieberman JR, et al. Prevention of symptomatic pulmonary embolism in patients undergoing total hip or knee arthroplasty. J Am Acad Orthop Surg. 2009;17:183-196.
• Lieberman JR, Barnes CL, Lachiewicz PD, et al. Venous thromboembolism debate in joint arthroplasty. J Bone Joint Surg (Am). 2009;91(Supplement_5):29-31.
• Millican EA, Lenzini PA, Milligan PE, et al. Genetic-based dosing in orthopedic patients beginning with warfarin therapy. Blood. 2007; 110(5):1511-1515.
• Novicoff WM, Brown TE, Cui Q, et al. Mandated venous thromboembolism prophylaxis: Possible adverse outcomes. J Arthroplasty. 2008;23(6 suppl):15-19.
• www.aaos.org/dvt
• www.spine.org
• Robert L. Barrack, MD, can be reached at 1 Barnes-Jewish Hospital Plaza, 11300 West Pavilion, St. Louis, MO 63110; 314-747-2562; e-mail: barrackr@wudosis.wustl.edu.
• Christopher M. Bono, MD, can be reached at Brigham & Women’s Hospital, Orthopaedic Surgery, 75 Francis St., Boston, MA 02115; 617-732-7238; e-mail: cmbono@parntners.org.
• William J. Maloney III, MD, can be reached at 450 Broadway, Pavilion C, 4th Floor, Redwood City, CA 94063; 650-723-1690; e-mail: wmaloney@stanford.edu.
• Andrew H. Schmidt, MD, can be reached at Hennepin Count Medical Center, Department of Orthopedic Surgery, 701 Park Ave., Minneapolis, MN 55415; 612-873-8595; e-mail: schmi115@umn.edu.

What is the role of aspirin as DVT prophylaxis in TJR surgery?

Use aspirin as drug of choice

Paul A. Lotke

Most total joint replacement surgery patients should have aspirin as the thromboembolic prophylaxis of choice, the only exception being those with known histories of prior PE or known thrombophilia. It has been well demonstrated, in numerous studies, that aspirin offers equal protection against PE as other agents. The problem is the perception that aspirin is not as effective as some of the more aggressive agents, such as Lovenox or Coumadin. However, its safety and ease of use more than compensate for this perception. As data accumulate, it becomes increasingly evident that aggressive chemoprophylactic agents cause more harm and do not appear to offer the benefits they are supposed to.

Comparing aspirin head-to-head with Coumadin, Lovenox and Lovenox-like drugs, we find aspirin is simple to use and can be maintained without monitoring for extended periods. Coumadin is relatively safe, but difficult and expensive to monitor. Lovenox and similar drugs are fairly expensive with significant risks of bleeding, the downsides of which have yet to be fully evaluated after TJR surgery.

In TJR, risks of PE are so low that to prove one agent is significantly more effective than another will be difficult without large studies. However, when we start to compare the major bleeding risks, which are anywhere from 3% to 5% with Lovenox-like drugs, we begin to see these agents are indeed potentially dangerous. We do not know the effect prolonged drainage, increased blood loss and wound issues have on TJR surgery outcomes. However, I would presume that if major bleeding risks are indeed 3% to 5%, this will significantly affect outcomes in the long run.

Paul A. Lotke, MD, is professor emeritus University of Pennsylvania and senior associate editor Clinical Orthopaedics and Related Research, Philadelphia, Pa.

More level-1 data for aspirin needed

Jay R. Lieberman

The selection of an agent for DVT prophylaxis after THA or TKA is a balance between safety and efficacy. It is clear from the available literature there are some very effective prophylactic agents, such as LMWH, warfarin and fondaparinux, but they are also associated with bleeding. Aspirin is not as potent a chemoprophylactic agent as these other drugs, however it seems to have less bleeding. The ideal strategy would be to risk stratify patients based on the risk of symptomatic DVT and PE, and bleeding.

Aspirin is an attractive prophylactic agent because it is an oral drug and there is excellent patient compliance. A number of retrospective cohort studies suggest it works well in the prevention of symptomatic PE. However, there are no recent multicenter randomized trials assessing its efficacy and safety. In order to determine its true efficacy, aspirin needs to be compared with either LMWH or fondaparinux in an appropriately powered, randomized trial assessing symptomatic events.

The SCIP has made recommendations for DVT prophylaxis after THA and TKA. Medicare now uses this information as a quality measure and hospitals are being held accountable for the type of prophylaxis used at their institutions. The agents approved for THA are warfarin, LMWH and fondaparinux, and for TKA they are warfarin, LMWH, fondaparinux and mechanical devices. Therefore it would be clearly acceptable to use aspirin and mechanical devices for prophylaxis after TKA. Aspirin does not meet SCIP guidelines for prophylaxis after THA. However, the surgeon can write a note in the chart stating that aspirin and mechanical devices were used for prophylaxis because of concerns about bleeding and this would be acceptable under the guidelines.

The ideal prophylaxis regimen would include risk stratification of each patient based on their risk of symptomatic PE and DVT and bleeding. However, since we do not have the data now to reliably stratify most patients, we currently provide maximal prophylaxis for most patients to adequately protect those requiring it.

Jay R. Lieberman, MD, is director of the New England Musculoskeletal Institute and chairman of the Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, Conn. He is a member of the Orthopedics Today Editorial Board.