CORR Insights®: What Proportion of Patients With Musculoskeletal Tumors Demonstrate Thromboelastographic Markers of Hypercoagulability? A Pilot Study

Where Are We Now?

Venous thromboembolism (VTE) after orthopaedic tumor surgery is potentially life-threatening; for patients who survive the event, there might be longer hospital stays, increased costs of care, and even long-term disability because of post-thrombotic symptoms [2]. In one systematic review, 2.9% of patients with soft tissue sarcoma experienced VTE after surgery, with 3.7% and 1.4% of VTEs occurring in patients with bone and soft tissue sarcomas, respectively [3]. Several risk factors for VTE have been reported, including disease load, functional status, ischemic heart disease as a comorbidity, maximum tumor diameter, elevated preoperative platelet count, administration of chemotherapy, and operative time [1, 4, 6, 9]. Additionally, patients with cancer are considered at an increased risk of VTE because all three components of the Virchow triad (hypercoagulability, hemodynamic changes, and endothelial injury or dysfunction) are often present as part of their condition [5]. Platelet activation owing to elevated levels of inflammatory cytokines from a tumor can result in hypercoagulability, a tumor mass can compress adjacent veins resulting in hemodynamic changes, and, of course, endothelial injury can occur because of surgical manipulation.

Of these, hypercoagulability is perhaps the most important to orthopaedic tumor surgeons because it can be treated. Specifically, we can adjust our approaches to the type, dose, and timing of chemical VTE prophylaxis. But determining which patients are especially at risk of hypercoagulability is challenging.

Meeting this challenge is an article in this month’s Clinical Orthopaedics and Related Research®, in which Sabharwal et al. [7] analyzed thromboelastography (TEG)-derived coagulation profiles in patients with orthopaedic oncologic conditions. They found that most patients undergoing surgery for sarcoma or metastatic bone disease in this pilot study had at least one abnormal TEG result; that older patients, women, and those with soft tissue sarcomas were more likely to have TEG-defined hypercoagulability; and that patients with TEG-related abnormalities were somewhat more likely to have a symptomatic clot. Although the findings in this pilot study warrant further research, I believe surgeons may be able to detect TEG-defined hypercoagulability in patients as a proxy measure for greater VTE suspicion. Moreover, the results of a TEG assay could help surgeons select the chemoprophylaxis regimen, such as an antiplatelet or heparin-family agent.

Where Do We Need To Go?

To the best of my knowledge, no consensus exists regarding the use of chemical VTE prophylaxis or the duration of treatment in patients with orthopaedic oncologic conditions. Although prophylactic drugs lower the risk of VTE, they may increase the risk of postoperative bleeding and wound complications. These risks are considered to be higher after orthopaedic oncology procedures because of the extent of tissue or blood vessel dissection, long duration of surgery, and use of neoadjuvant chemotherapy and/or radiotherapy [4]. Developing recommendations about how and when to use these drugs would be helpful; any such recommendations should consider whether the chosen prophylactic drug is reversible, because this may be important in patients who must return to the operating room urgently (protamine sulfate for heparins, vitamin K for warfarin, or andexanet alfa for factor Xa inhibitors).

In the meantime, surgeons need to balance the risk of VTE and bleeding or wound complications when they make decisions regarding the type of chemical VTE prophylaxis, dose, and timing. Patients with orthopaedic oncologic conditions sometimes return to the operating room owing to a postoperative infection, wound complications, or bleeding. Future studies could help us better characterize the real risk of postoperative bleeding and wound complications that are related to the use of thromboprophylactic drugs.

How Do We Get There?

Further research is required to calculate the postoperative VTE risk accurately and determine the most effective chemical VTE prophylaxis regimen and whether individualized thromboprophylaxis is required. A sufficient cohort and a multivariable analysis in a multicenter collaboration would help us characterize patient and disease risk factors for hypercoagulability and VTE. A TEG assay would help define hypercoagulability as a proxy measure for a patient’s predisposition to VTE. Risk calculators or a nomogram that use inputs of patient demographic characteristics, including a TEG assay and/or comorbidities to predict the risk of VTE, can be developed based on these data. Machine-learning algorithms may contribute to accurate risk calculations based on their ability to capture complex, nonlinear relationships in large datasets [8]. A multicenter collaborative study (ideally prospective and randomized) might offer information about the most effective regimen for patients with primary sarcoma or bone metastasis who undergo major surgery, the optimal duration of thromboprophylaxis to be used, and whether individualized VTE prophylaxis is required. Distinguishing hypercoagulability driven by platelet hyperfunction and hypercoagulability driven by enzymatic hyperactivity that catalyzes fibrin crosslinking may inform the selection of chemoprophylaxis drugs (antiplatelet or anticoagulant) based on information derived from TEG [7].