Venous thromboembolism (VTE) following hip fractures and hip/knee arthroplasty—both deep vein thrombosis (DVT) and pulmonary embolism (PE)—has been relatively well studied. We therefore have a fairly clear understanding what the risks for DVT and PE are with no treatment as well as with modern preventive chemotherapeutic agents. However, such clarity on the need for and effectiveness of VTE prophylaxis is lacking for below-the-knee (BTK) orthopaedic procedures. This is largely due to the fact that such procedures have been deemed “low risk”—despite a dearth of supporting evidence for that assumption. In the March 20, 2019 issue of The Journal, Heijboer et al. used a sophisticated propensity score matching methodology to evaluate the rate of VTE in >10,000 BTK surgery patients at their tertiary care referral center.
The authors evaluated patients who underwent orthopaedic surgery distal to the proximal tibial articular surface, including foot/ankle procedures, open reduction of lower-leg fractures, and BTK amputations. They performed propensity score matching to compare 5,286 patients who received any type of chemotherapeutic prophylaxis with the same number who did not, across several key risk categories. The good news is that VTE prophylaxis effectively lowered the risk of symptomatic DVT or PE from 1.9% to 0.7% (odds ratio of 0.38, p <0.001).
Unfortunately (but not surprisingly), this effectiveness came at the price of increased systemic or local bleeding among patients using chemical VTE prophylaxis, with an incidence of 1.0% in the no-prophylaxis group and 2.2% in the prophylaxis group (odds ratio of 2.18, p <0.001). The authors did not assess the incidence of deep infection or hematoma formation, which often accompany increased local bleeding. The low overall incidence of VTE and bleeding did not allow for subgroup analysis according to location of surgery, and aspirin use was not controlled for in their study. In addition, Heijboer et al. used hospital coding data, and the accuracy of the database was not assessed.
The authors recommend that “anticoagulant prophylaxis be reserved only for patient groups who are deemed to be at high risk for VTE,” but we still don’t know precisely who is at high risk among BTK surgery patients. It is my hope that these findings will prompt large, prospective multicenter trials in the foot and ankle community to better determine which types of patients should be exposed to an increased risk of postoperative bleeding complications in order to achieve a clinically important decreased risk of VTE with chemical prophylaxis.
Marc Swiontkowski, MD
OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Matthew Herring, MD in response to a recent study in the Journal of Orthopaedic Trauma.
Pulmonary embolism (PE) is a potentially life-threatening complication among many orthopaedic trauma patients. PE can be a silent killer, with only about 30% of fatal PEs being detected before death. Chemical prophylaxis with “blood thinners” such as injectable enoxaparin is effective in mitigating the risk of PE, but in the poly-traumatized patient, its application is often contraindicated. In an effort to develop a more effective approach to PE prevention in the trauma population, Starr et al. built a tool to estimate the risk of PE early and effectively, and then developed a multidisciplinary protocol for deep vein thrombosis (DVT) prophylaxis. They present their preliminary experience with the risk-assessment tool and the new protocol in the February 2019 issue of the Journal of Orthopaedic Trauma.
The smart-phone app (ParkLandOrtho) to risk-stratify trauma patients in the ED is based on 7 easily captured variables that the authors’ prior work identified as statistically significant predictors for developing a PE. Patients who are identified as “high risk” are aggressively started on enoxaparin, with the first dose ideally given prior to ED discharge. If contraindications for chemical prophylaxis are present, enoxaparin is withheld for up to 24 hours after admission. After 24 hours, if the patient is still unable to receive enoxaparin, a removable inferior vena cava (IVC) filter is placed.
The authors performed a retrospective review of PE incidence among 368 consecutive orthopaedic trauma patients admitted to their hospital after this new protocol was implemented and compared it to PE incidence among a historic cohort of 420 similar consecutive patients admitted during the year prior to the protocol. The two groups were similar in age and injury severity. In the control group, 51 patients were retrospectively classified as high risk, and 9 patients (2.1%) developed symptomatic PEs, one of which was fatal. In the group managed under the new protocol, 40 patients were identified as high risk, and only 1 patient (0.27%) developed a nonfatal PE. The difference in incidence of PE between the two groups was statistically significant (P = 0.02).
This paper highlights two significant achievements in my opinion. First, I was excited to see the success of a smart-phone app to facilitate rapid risk assessment. This was a significant key to the success of the multidisciplinary PE protocol, which depends on buy-in and compliance. Second, this thoughtful, decisive, and team-based protocol for DVT/PE prophylaxis in an orthopaedic trauma setting seems to be making a meaningful impact on patient outcomes.
The authors report that they are currently designing a multicenter trial to prospectively validate their protocol. I eagerly await this and hope that their next step includes a ParklandOrtho app release for Android devices, as it is only available now for iPhone and Samsung users.
Matthew Herring, MD is a fellow in orthopaedic trauma at the University of California, San Francisco and a member of the JBJS Social Media Advisory Board.
Prior research has established that total hip arthroplasty (THA), in and of itself, is associated with a small increased risk of venous thromboembolism (VTE). Hence the concern that routinely administering the antifibrinolytic drug tranexamic acid (TXA) perioperatively, as is commonly done nowadays to reduce blood loss during surgery, might further increase the risk of THA-related thromboembolic events. But the findings from a large population-based cohort study by Dastrup et al. in the October 17, 2018 JBJS, should allay many of those concerns.
The authors evaluated >45,000 Danish patients who had a THA between 2006 and 2013. Approximately 85% of those patients received intravenous TXA perioperatively, while the rest did not. Dastrup et al. evaluated adverse cardiovascular events (VTE, deep venous thrombosis, pulmonary embolism, myocardial infarction, and ischemic stroke) among those patients over 30 postoperative days, and they found no increased risk in any of those outcomes among the patients who received TXA relative to those who did not. These optimistic findings were essentially the same when the authors analyzed the data using a multivariable model and with propensity-score matching.
Dastrup et al. conclude that TXA in the setting of THA is safe with respect to VTE, and David Ayers, MD, commenting on the study, concurs. However, Dr. Ayers cautions that the study did not have the statistical strength to evaluate the potential cardiovascular risks of TXA in THA patients who have undergone previous cardiac procedures, such as stent placement. He therefore suggests that “further safety evaluation should be directed toward [such] patients at higher risk for complications after receiving TXA.”
Minimizing perioperative blood loss during total knee arthroplasty (TKA) helps curtail the risks and costs of allogeneic blood transfusions. Currently, the most popular pharmacological approach to blood conservation is the antifibrinolytic agent tranexamic acid (TXA). But in a randomized trial published in the October 4, 2017 edition of The Journal of Bone & Joint Surgery, Boese et al. found that a similar and much less expensive compound, epsilon-aminocaproic acid (EACA), performed almost as effectively and just as safely as TXA in patients undergoing unilateral knee replacement.
Although the 98 patients in the study who received TXA averaged less estimated blood loss than the 96 patients who received EACA, no transfusions were required in either group, and there were no statistically significant or clinically relevant between-group differences in the change in hemoglobin levels. On the safety/complication side, there were no statistically significant between-group differences in any measured parameter, including postoperative serum creatinine levels or renal, bleeding, or thrombotic complications. However, there were 3 pulmonary emboli in the EACA group compared with only 1 in the TXA group. While that was not a statistically significant difference, “an observed difference of this magnitude could limit the usefulness of EACA in TKA,” the authors caution.
This study did not compare the current cost of the two compounds, but back in 2012, when the authors’ institution added antifibrinolytics to their blood management program, TXA cost $43/g, compared with $0.20/g for EACA. The cost differential is striking, even when you consider that TXA is at least 7 times more potent than EACA on a molar basis, so less of the former drug is required.
Boese et al. conclude that “TXA does not have superior blood conservation effects or safety profile compared with EACA in TKA,” but they cite a need for future equivalence, superiority, and noninferiority trials with these drugs.
In the February 15, 2017 issue of The Journal, Aneja et al. utilize a large administrative database to examine the critical question of venous thromboembolism (VTE) risk as it relates to managing patients with metastatic femoral lesions. The authors found that prophylactic intramedullary (IM) nailing clearly resulted in a higher risk of both pulmonary embolism and deep-vein thrombosis, relative to IM nailing after a pathologic fracture. Conversely, the study found that patients managed with fixation after a pathological fracture had greater need for blood transfusions, higher rates of postoperative urinary tract infections, and a decreased likelihood of being discharged to home.
The VTE findings make complete clinical sense, because when we ream an intact bone, the highly pressurized medullary canal forces coagulation factors into the peripheral circulation. When we ream after a fracture, the pressures are much lower, and neither the coagulation factors nor components of the metastatic lesion are forced into the peripheral circulation as efficiently, although some may partially escape through the fracture site.
One might conclude that we should never consider prophylactic fixation in the case of metastatic disease in long bones, but that would not be a patient-centric position to hold. In my opinion, the decision about whether to prophylactically internally fix an impending pathologic fracture should be based on patient symptoms and consultations with the patient’s oncologist and radiation therapist.
If all of the findings from Aneja et al. are considered, and if the patient’s symptoms are functionally limiting after initiation of appropriate radiation and chemotherapy, prophylactic fixation should be performed, along with vigilantly managed VTE-prevention measures. This study is ideally suited to inform these discussions for optimum patient care.
Marc Swiontkowski, MD