The recent orthopaedic literature, including a 2017 JBJS study, provides substantial evidence that oral and intravenous tranexamic acid (TXA) are equivalent in their effectiveness at reducing blood loss after total hip arthroplasty (THA)—with oral administration being less expensive and more convenient. But what are the optimal doses and timing of oral TXA in the setting of THA?
The findings of a randomized controlled trial by Wang et al. in the March 6, 2019 issue of JBJS go a long way toward answering that question. The authors randomized 200 patients undergoing primary THA to 1 of 4 groups, with all patients receiving an intraoperative topical dose of 1.0 g of TXA and a single dose of 2.0 g of TXA orally at 2 hours postoperatively. In addition,:
- Group A received 1.0 g of oral placebo at 3, 9, and 15 hours postoperatively
- Group B received 1.0 g of oral TXA at 3 hours postoperatively and 1.0 g of placebo at 9 and 15 hours postoperatively
- Group C received 1.0 g of oral TXA at 3 and 9 hours postoperatively and 1.0 g of placebo at 15 hours postoperatively
- Group D received 1.0 g of TXA at 3, 9, and 15 hours postoperatively
The mean total blood loss during hospitalization was significantly less in Groups B, C, and D (792, 631, and 553 mL, respectively) than in Group A (984 mL). Groups C and D had lower mean reductions in hemoglobin than did Groups A and B. No significant between-group differences were observed regarding 90-day thromboembolic complications (there were none) or transfusions (there was only 1, in Group A), but the authors said “this study was likely underpowered for establishing meaningful comparisons concerning [those 2] outcomes.”
Although this study documented significantly lower total blood losses in patients who were managed with multiple doses of oral TXA postoperatively, additional studies are required to determine whether the 3-dose regimen is superior to the 2-dose regimen.
Perioperative anticoagulation for patients undergoing orthopaedic surgery remains a challenge. Currently, there is insufficient evidence to provide definitive recommendations for care. Recent estimates suggest that, in the U.S. alone, there are over two million patients with atrial fibrillation who receive warfarin each year. Moreover, >100,000 heart valve replacements are performed annually.
In the September 2015 issue of JBJS Reviews, Dundon et al. review current recommendations for perioperative management of patients on existing anticoagulation therapy. They note that cessation of warfarin is based on risk stratification for thromboembolic events and bleeding risk, with cessation and bridging therapy being recommended if patients are at high risk for thromboembolic events or bleeding. On the basis of their assessment of published reports, they recommend that warfarin should be withdrawn and that bridging therapy should be instituted five days prior to surgery. Cessation and regular dosing should be resumed twelve to twenty-four hours after the operation.
However, the issue of perioperative bridging is currently under debate. The authors of this article could find no double-blind, randomized, controlled trials in which patients undergoing vitamin-K antagonist therapy who had received bridging with low-molecular-weight heparin or unfractionated heparin were compared with patients undergoing vitamin-K antagonist therapy who had received no bridging therapy. Bridging therapy with therapeutic-dose intravenous unfractionated heparin should be stopped four to six hours before surgery, but patients receiving therapeutic-dose subcutaneous low-molecular-weight heparin should take the last dose approximately twenty-four hours prior to surgery.
The authors recommended that patients in high cerebrovascular and cardiovascular risk groups should maintain aspirin with bridging therapy and may also maintain clopidogrel in emergencies as long as they are not undergoing a high-risk procedure. For patients who take rivaroxaban or dabigatran, emergency surgery is permissible as long as levels of the drug are ≤30 ng/mL at the time of admission.
These recommendations are based on careful and critical analyses of available data; however, as noted above, there are no critical evidence-based studies in the area of perioperative management of anticoagulation in patients who are undergoing orthopaedic surgery. The concepts and ideas presented in this article should be considered as recommendations at best.
Thomas Einhorn, Editor
Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Here is a summary of selected findings from Level I and II studies cited in the June 17, 2015 Specialty Update on spine surgery:
- A database study to determine the prevalence of venous thromboembolic events after spinal fusion found that risk factors for such events included hypercoagulability, certain medical comorbidities, older age, and male sex.
- An RCT comparing allograft alone versus allograft plus bone marrow concentrate to accomplish spine fusion in adults with spondylolisthesis found very poor union rates in both groups, although allograft with bone marrow concentrate delivered slightly better results.
- A meta-analysis of five studies (253 patients) found no pain or functional differences when unilateral percutaneous kyphoplasty was compared with bilateral (same-vertebra) kyphoplasty for osteoporotic compression fractures. The unilateral approach was associated with shorter operative times, however.
- An RCT comparing the analgesic efficacy and clinical utility of gabapentin, pregabalin, and placebo in patients undergoing spinal surgery found that pregabalin outperformed the other two interventions immediately after surgery postoperative and up to three months postoperatively.
- In an RCT comparing open-door to French-door laminoplasty for cervical compressive myelopathy, both techniques were found to be equivalent in terms of neurological recovery and perioperative complications, but patients receiving the open-door technique had more kyphosis and less cervical range of motion postoperatively.
- An update to a 2002 Cochrane review found no significant outcome differences between supervised and home-exercise rehabilitation programs after lumbar disc surgery.
- A systematic review/meta-analysis showed that radiofrequency denervation of facet joints is more effective than placebo in achieving functional improvement and pain control in patients with chronic low back pain.
- A Level II diagnostic study concluded that with a magnification of 150% and a good pair of flexion and extension radiographs following anterior cervical arthrodesis, pseudarthrosis was noted with >1 mm of motion between fused interspinous processes with 96.1% specificity and a positive predictive value of 96.9%.
- A Level I therapeutic study comparing the efficacy of intravenous tranexamic acid, epsilon-aminocaproic acid, and placebo to reduce bleeding in 125 adolescent patients undergoing posterior fusion for idiopathic scoliosis found less intraoperative and postoperative blood loss and higher hematocrit levels with the antifibrinolytics than with placebo. However, transfusion requirements were no different between the groups.
- A randomized comparison of navigated versus freehand techniques for pedicle screw insertion during lumbar procedures found that surgeon radiation exposure with freehand technique is up to 10 times greater than with use of navigation.
The overall rate of symptomatic lower-extremity deep vein thrombosis (DVT) following arthroscopic ACL procedures is reported to be <0.3%, and guidelines from the American College of Chest Physicians recommend against DVT prophylaxis prior to arthroscopic knee surgery, unless a patient has risk factors for blood clots. But some patients are unknowingly at high risk for clots, as a case report by Ackerman et al. in the June 10, 2105 JBJS Case Connector shows.
A 45-year-old woman presented for arthroscopic ACL reconstruction in her left knee. Unbeknownst to her or her surgeons, the patient had asymptomatic May-Thurner syndrome—an anatomic variant of the iliac blood vessels in which the right common iliac artery crosses over the left common iliac vein, compressing the vein against the lumbar spine.
Nine days after ACL surgery, the patient showed up in the ED with pain and swelling in the operative leg. Ultrasound revealed an extensive DVT extending distally from the common femoral vein. Imaging of the chest and cardiac workups were negative for heart or lung thromboembolism.
A heparin drip was started, and a vascular surgeon ordered a left-leg venograph, which revealed a large clot extending from the origin of the left common iliac vein to the insertion site of the catheter in the popliteal vein. Severe stenosis of the left common iliac vein confirmed May-Thurner syndrome (see image below).
Treatment consisted of an infusion of tissue plasminogen activator (Alteplase) directly to the clot, continued intravenous heparin, and an angioplasty with stents to open the stenosed left common iliac vein. Mechanical thrombolysis and aspiration of a residual femoral vein thrombus was accomplished with a Trellis device.
Postoperatively the patient was transitioned to therapeutic warfarin for six months and instructed to wear compression stockings. She completed her ACL physical therapy protocol uneventfully, and one year after the ACL reconstruction, the knee graft was stable and there was no evidence of post-thrombotic syndrome.
The authors remind orthopaedists that May-Thurner syndrome, which is more common in women than men, should be suspected in the presence of an extensive iliofemoral DVT. They emphasize that multimodal and aggressive treatment, in consultation with a vascular specialist, should be initiated to bust the clot and reduce the risk of post-thrombotic syndrome. Post-clot, such patients should be maintained on warfarin for a minimum of six months, and patients with stents often require lifelong aspirin therapy.
The venographic prevalence of deep vein thrombosis in people with distal lower-extremity injuries that require surgery or casting ranges from 10% to 40%. But a prospective cohort study in the May 21, 2014 JBJS found that only 0.6% of 1200 patients with lower-leg fractures and no medical or mechanical thromboprophylaxis had symptomatic, objectively confirmed venous thromboembolism (VTE) over a 12-week follow-up. Moreover, none of the seven thrombotic complications was fatal. This leads the authors to conclude that “the risk-benefit ratio and cost effectiveness of routine anticoagulant prophylaxis are unlikely to be favorable for these patients.” They go on to say that despite the large sample size in this study, the low prevalence of VTE made it impossible to pinpoint characteristics that could identify a subgroup of similar patients who might be at higher risk of clotting problems.
With 840 scientific presentations, 560 posters, and 200 instructional course lectures, even OrthoBuzz couldn’t comprehensively summarize the 2014 AAOS Annual Meeting in New Orleans. But here’s a small random sampling of findings reported at the meeting that you might find interesting. Please remember that these data have not appeared in peer-reviewed journals and should be considered preliminary.
TENS for Low Back Pain Could Save Medicare Nearly a Half-Billion Dollars
If all of its estimated 1.5 million beneficiaries with chronic low back pain were treated with TENS—transcutaneous electrical nerve stimulation—Medicare could save about $417 million in annual treatment costs, said Michael Minshall, MPH (paper #474). The figures are based partly on published research showing that TENS patients use significantly fewer health care resources (hospital and office visits, imaging, physical therapy, and surgery) than those receiving other treatments.
Allografts Fail Three Times More Frequently than Autografts in Primary ACL Reconstruction
A prospective randomized trial of 99 ACL reconstruction patients in their twenties revealed a 10-year 26.5% failure rate when tibialis posterior tendon allografts were used, compared with an 8.5% failure rate for hamstring autografts. Presenter Craig Bottoni, MD (paper # 462) said both groups received the same fixation technique and the same postoperative rehab program by physical therapists who were blinded to the treatment allocation.
Tranexamic Acid Cuts Transfusion Rates during TJA without Boosting VTEs
Scott Wingerter, MD (paper #1) presented data from Washington University School of Medicine (WUSM) showing that transfusion rates declined substantially during primary and revision hip and knee replacement procedures after tranexamic acid began being used routinely at WUSM. The incidence of venous thromboembolism was also lower in the group that received tranexamic acid, although that difference was not statistically significant.
Repeat Skin Antisepsis May Reduce Surgical Site Infections
A randomized, prospective study of nearly 600 patients undergoing total joint replacement found that those who received additional skin antisepsis with an iodine povacrylex/alcohol combination after surgical draping but before incise draping were far less likely to experience a superficial surgical site infection than those who received standard skin preparation with chlorhexidine, alcohol, and betadine. Presenter Tiffany Morrison, MS (paper # 49) also noted a non-significant difference in rates of skin blistering between the two groups.