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Published 5/1/2009
Jennie McKee

Keeping blood clots at bay after TJA

Current prophylaxis has limitations; new medications hold potential for advances

“For 20 years, we’ve been aggressively trying to prevent venous thromboembolic disease, but there’s still no clear consensus on which prophylactic agents are best and which should be avoided,” said Fred D. Cushner, MD.

Dr. Cushner was one of a panel of experts at the 2009 AAOS Annual Meeting that discussed the pros and cons of currently available prophylaxis, explained existing clinical practice guidelines, and discussed two new oral agents that may be more effective in preventing the development of potentially fatal blood clots in total joint arthroplasty (TJA) patients.

“Although not approved for clinical use in the United States, dabigatran, a direct thrombin inhibitor, and rivaroxaban, a Factor Xa inhibitor, have been approved for clinical use in Canada and Europe,” said Richard J. Friedman, MD.

Problems with current prophylaxis
Patients receive prophylaxis to prevent the development of fatal and nonfatal pulmonary embolisms (PE) and deep vein thrombosis (DVT), as well as potential complications such as recurrent DVT, chronic venous stasis disease, and chronic pulmonary hypertension.

According to Dr. Cushner, each prophylactic agent has limitations. Low molecular weight heparins (LMWHs) are high in efficacy and have no food or drug interactions. Patients are given an injection, he said, and are protected within 1 to 2 hours.

“But LMWH medications have a perceived risk of bleeding,” he said. “We can debate whether it’s a real or perceived risk—but in either case, many doctors are afraid to prescribe them.”

Warfarin, a drug that has long been used as a prophylaxis, also has its drawbacks, including dosing issues.

“Earlier hospital discharges make it hard for physicians to find the proper dose of warfarin,” said Dr. Cushner. “Patients often used to stay in the hospital for 7 to 10 days after TJA, which gave physicians time to determine the appropriate dose. Now, patients are going home 3 or 4 days after surgery.”

Dr. Cushner explained that these shorter hospital stays make it much more difficult to achieve the right international normalized ratio (INR), which measures the impact of the anticoagulant in the blood.

“In fact,” he said, “some studies show that 75 percent of patients do not reach an acceptable INR before they go home.”

Questions also exist regarding the efficacy of aspirin as a prophylaxis, even when its use is combined with compression hose, because aspirin tends to be a more effective prophylaxis for arterial, rather than venous, diseases.

“The bottom line is that consensus doesn’t exist—if you poll a group of orthopaedic surgeons, you’ll come up with numerous different prophylaxis protocols,” said Dr. Cushner.

Current guidelines
That lack of consensus is one reason the AAOS established its guidelines on the prevention of symptomatic PE in patients undergoing total hip or knee arthroplasty, noted Paul F. Lachiewicz, MD. Both the Joint Commission and the American College of Chest Phys­icians have also issued guidelines.

Dr. Lachiewicz, who was part of the work group that created the AAOS guidelines, said that the guide­lines state that patients should be assessed for their risk of PE and/or bleeding before undergoing surgery.

“We also believe that every patient should have mechanical prophylaxis—meaning some type of compression of their leg veins to prevent clots—starting either intraoperatively or immediately postoperatively,” said Dr. Lachiewicz. “Early mobilization should be encouraged; patients should be discharged rapidly and educated on the symptoms of DVT and PE.”

A patient who is at a high risk for clotting should receive stronger pharmaceutical prophylaxis, in addition to mechanical prophylaxis.

“If the patient is at standard risk for clots, but at high risk for bleeding because the surgeon has performed a very complicated surgery,” he explained, “the risk [of prophylaxis] may outweigh the benefits to the patient. Con­sequently, the dosage should be left up to the surgeon’s judgment.”

The AAOS guideline on the prevention of pulmonary embolism in patients undergoing total hip or knee arthroplasty is available online at www.aaos.org/guidelines

Prophylactic agents on the horizon
Important unmet clinical needs exist in current prophylaxis, said Dr. Friedman, who moderated the panel.

“No option currently exists that combines all the advantages with­out the drawbacks,” said Dr. Friedman. “We’re looking for an effective, inexpensive, easy-to-administer agent that does not require any monitoring and has relatively few complications or side-effects—that would be the ideal agent.”

Two new groups of oral agents—direct thrombin inhibitors and Factor Xa inhibitors—come in pill form and are designed to be taken once a day.

Dr. Friedman explained that these drugs offer a fixed dose, so they don’t require any monitoring or dose adjustments.

“Also, the risk for food or drug interaction is relatively low, which is a big improvement over some of the other medications,” he said.

Data from a pooled analysis of three studies found that dabigatran was as efficacious as enoxaparin, an LMWH, in preventing clots after hip and knee replacement.

“The direct thrombin inhibitor showed a relatively low rate of bleeding when compared to the LMWH and did not show any difference regarding liver enzymes or cardiac events,” he said.

“Significant inconsistencies between clinical practice and published guidelines continue. We need new agents with improved efficacy, a more attractive risk-to-benefit profile, convenient dosing and administration, and no requirement for monitoring,” concluded Dr. Friedman. “New oral anticoagulants with similar or superior efficacy, similar safety profiles, and no need for monitoring may offer a cost-effective alternative to currently available prophylaxes.”

The panelists disclosed the following conflicts: Dr. Cushner—Angiotech, Bayer, Clearant, Linvatec, Sanofi-Aventis Smith & Nephew, and Zimmer; Dr. Friedman—Astellas US, Boehringer Ingelheim, DJO Surgical, Johnson & Johnson, and Sanofi-Aventis; Dr. Lachiewicz—Covidien, DJO Global, Innomed, and Zimmer.

Jennie McKee is a staff writer for AAOS Now. She can be reached at mckee@aaos.org