What Proportion of Patients With Musculoskeletal Tumors Demonstrate Thromboelastographic Markers of Hypercoagulability? A Pilot Study
Authors: Sabharwal Samir , Jalloh Hulai B. , Levin Adam S. , Morris Carol D. 
Published: July 2022

Abstract

Background
Thromboelastography (TEG) is a point-of-care venipuncture test that measures the elasticity and strength of a clot formed from a patient’s blood, providing a more comprehensive analysis of a patient’s coagulation status than conventional measures of coagulation. TEG includes four primary markers: R-time, which measures the time to clot initiation and is a proxy for platelet function; K-value, which measures the time for said clot to reach an amplitude of 20 mm and is a proxy for fibrin cross-linking; maximum amplitude (MA), which measures the clot’s maximum amplitude and is a proxy for platelet aggregation; and LY30, which measures the percentage of clot lysis 30 minutes after reaching the MA and is a proxy for fibrinolysis. Analysis of TEG-derived coagulation profiles may help surgeons identify patient-related and disease-related factors associated with hypercoagulability. TEG-derived coagulation profiles of patients with musculoskeletal oncology conditions have yet to be characterized.

Questions/purposes
(1) What TEG coagulation profile markers are most frequently aberrant in patients with musculoskeletal oncology conditions presenting for surgery? (2) Among patients with musculoskeletal oncology conditions presenting for surgery, what factors are more common in those with TEG-defined hypercoagulability? (3) Do patients with musculoskeletal oncology conditions with preoperative TEG-defined hypercoagulability have a higher postoperative incidence of clinically symptomatic venous thromboembolism (VTE) than those with a normal TEG profile?

Methods
In this retrospective, pilot study, we analyzed preoperatively drawn TEG assays on 52 patients with either primary bone sarcoma, soft tissue sarcoma, or metastatic disease to bone who were scheduled to undergo either tumor resection or nail stabilization. Between January 2020 and December 2021, our orthopaedic oncology service treated 410 patients in total. Of these, 13% (53 of 410 patients) had preoperatively drawn TEG assays. TEG assays were collected preincision as part of a division initiative to integrate the assay into a clinical care protocol for patients with primary bone or soft tissue sarcoma or metastatic disease to bone. Unfortunately, failures to adequately communicate this to our anesthesia colleagues on a consistent basis resulted in a low overall rate of assay draws from eligible patients. One patient on therapeutic anticoagulation preoperatively for the treatment of active VTE was excluded, leaving 52 patients eligible for analysis. We did not exclude patients taking prophylactic antiplatelet therapy preoperatively. All patients were followed for a minimum of 6 weeks postoperatively. We analyzed factors (age, sex, tumor location, presence of metastases, and soft tissue versus bony disease) in reference to hypercoagulability, defined as a TEG result indicating supranormal clot formation (for example, reduced R-time, reduced K-value, or increased MA). Patients with clinical concern for deep vein thrombosis (DVT) (typically painful swelling of the affected extremity) or pulmonary embolism (typically by dyspnea, tachycardia, and/or chest pain) underwent duplex ultrasonography or chest CT angiography, respectively, to confirm the diagnosis. Categorical variables were analyzed via a Pearson chi-square test and continuous variables were analyzed via t-test, with significance defined at α = 0.05.

Results
Overall, 60% (31 of 52) of patients had an abnormal preoperative TEG result. All abnormal TEG assay results demonstrated markers of hypercoagulability. The most frequent aberration was a reduced K-value (40% [21 of 52] of patients), followed by reduced R-time (35% [18 of 52] of patients) and increased MA (17% [9 of 52] of patients). The mean ± SD TEG markers were R-time: 4.3 ± 1.0, K-value: 1.2 ± 0.4, MA: 66.9 ± 7.7, and LY30: 1.0 ± 1.2. There was no association between hypercoagulability and tumor location or metastatic stage. The mean age of patients with TEG-defined hypercoagulability was higher than those with a normal TEG profile (44 ± 23 years versus 59 ± 17 years, mean difference 15 [95% confidence interval (CI) 4 to 26]; p = 0.01). In addition, female patients were more likely than male patients to demonstrate TEG-defined hypercoagulability (75% [18 of 24] of female patients versus 46% [13 of 28] of male patients, OR 3.5 [95% CI 1 to 11]; p = 0.04) as were those with soft tissue disease (as opposed to bony) (77% [20 of 26] of patients with soft tissue versus 42% [11 of 26] of patients with bony disease, OR 4.6 [95% CI 1 to 15]; p = 0.01). Postoperatively, symptomatic DVT developed in 10% (5 of 52; four proximal DVTs, one distal DVT) of patients, and no patients developed symptomatic pulmonary embolism. Patients with preoperative TEG-defined hypercoagulability were more likely to be diagnosed with symptomatic postoperative DVT than patients with normal TEG profiles (16% [5 of 31] of patients with TEG-defined hypercoagulability versus 0% [0 of 21] of patients with normal TEG profiles; p = 0.05). No patients with normal preoperative TEG profiles had clinically symptomatic VTE.

Conclusion
Patients with musculoskeletal tumors are at high risk of hypercoagulability as determined by TEG. Patients who were older, female, and had soft tissue disease (as opposed to bony) were more likely to demonstrate TEG-defined hypercoagulability in our cohort. The postoperative VTE incidence was higher among patients with preoperative TEG-defined hypercoagulability. The findings in this pilot study warrant further investigation, perhaps through multicenter collaboration that can provide a sufficient cohort to power a robust, multivariable analysis, better characterizing patient and disease risk factors for hypercoagulability. Patients with TEG-defined hypercoagulability may warrant a higher index of suspicion for VTE and careful thought regarding their chemoprophylaxis regimen. Future work may also evaluate the effectiveness of TEG-guided chemoprophylaxis, as results of the assay may inform selection of antiplatelet versus anticoagulant agent.

Level of Evidence
Level III, therapeutic study.