Department of Orthopaedic Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
Clin Orthop Relat Res. 2023 Mar 1;481(3):553-561. doi: 10.1097/CORR.0000000000002314. Epub 2022 Jul 12.
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?
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.
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.
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 III, therapeutic study.
血栓弹力图（TEG）是一种即时的静脉采血检测，可测量患者血液形成的血凝块的弹性和强度，提供比传统凝血检测更全面的凝血状态分析。TEG 包括四个主要指标：R 时间，测量血小板功能的凝血起始时间；K 值，测量凝血达到 20mm 振幅的时间，代表纤维蛋白交联；最大振幅（MA），测量血凝块的最大振幅，代表血小板聚集；LY30，测量 MA 达到后 30 分钟时血凝块的溶解百分比，代表纤维蛋白溶解。分析 TEG 衍生的凝血谱可能有助于外科医生识别与高凝状态相关的患者相关和疾病相关因素。患有肌肉骨骼肿瘤疾病的患者的 TEG 衍生凝血谱尚未得到描述。
问题/目的：（1）接受手术的肌肉骨骼肿瘤患者最常出现哪些 TEG 凝血指标异常？（2）在接受手术的肌肉骨骼肿瘤患者中，TEG 定义的高凝状态更常见于哪些因素？（3）术前 TEG 定义的高凝状态的肌肉骨骼肿瘤患者术后出现有症状的静脉血栓栓塞症（VTE）的发生率是否高于 TEG 谱正常的患者？
在这项回顾性的、试点研究中，我们分析了 52 名接受肿瘤切除术或骨钉稳定术的原发性骨肉瘤、软组织肉瘤或转移性骨肿瘤患者的术前 TEG 检测。在 2020 年 1 月至 2021 年 12 月期间，我们的骨科肿瘤服务部门共治疗了 410 名患者。其中，13%（53 名）的患者接受了术前 TEG 检测。TEG 检测作为一项科室倡议，在术前作为切口切开的一部分进行，目的是将该检测纳入原发性骨或软组织肉瘤或转移性骨肿瘤患者的临床护理方案中。不幸的是，未能将这一信息持续、一致地传达给我们的麻醉科同事，导致有资格接受检测的患者总体检测率较低。一名因活动性 VTE 接受术前抗凝治疗的患者被排除在外，留下 52 名符合分析条件的患者。我们没有排除术前接受预防性抗血小板治疗的患者。所有患者术后至少随访 6 周。我们分析了年龄、性别、肿瘤位置、转移情况、软组织与骨肿瘤等因素与高凝状态的关系，高凝状态定义为 TEG 结果显示异常的凝块形成（例如，R 时间缩短、K 值缩短或 MA 增加）。有深部静脉血栓形成（DVT）（通常是受累肢体疼痛性肿胀）临床症状或疑似肺栓塞（通常表现为呼吸困难、心动过速和/或胸痛）的患者分别接受了双功超声或胸部 CT 血管造影以确诊。使用 Pearson 卡方检验分析分类变量，使用 t 检验分析连续变量，以 α = 0.05 为显著水平。
总体而言，60%（31/52）的患者术前 TEG 检测结果异常。所有异常 TEG 检测结果均显示高凝状态的标志物。最常见的异常是 K 值降低（40%[52 例患者中的 21 例]），其次是 R 时间缩短（35%[52 例患者中的 18 例]）和 MA 增加（17%[52 例患者中的 9 例]）。平均±SD TEG 标志物为 R 时间：4.3±1.0，K 值：1.2±0.4，MA：66.9±7.7，LY30：1.0±1.2。高凝状态与肿瘤位置或转移阶段无相关性。TEG 定义的高凝状态患者的平均年龄高于 TEG 谱正常的患者（44±23 岁与 59±17 岁，平均差异 15[95%置信区间（CI）为 4 至 26]；p=0.01）。此外，女性患者比男性患者更有可能表现出 TEG 定义的高凝状态（75%[24 名女性患者中的 18 名]与 46%[28 名男性患者中的 13 名]，OR 3.5[95%CI 1 至 11]；p=0.04），患有软组织疾病（而不是骨疾病）的患者比患有骨疾病的患者更有可能表现出 TEG 定义的高凝状态（77%[26 名患者中的 20 名]与 42%[26 名患者中的 11 名]，OR 4.6[95%CI 1 至 15]；p=0.01）。术后，10%（5/52；4 例近端 DVT，1 例远端 DVT）的患者出现有症状的 DVT，无患者出现有症状的肺栓塞。术前 TEG 定义的高凝状态患者术后发生有症状的 DVT 的可能性高于 TEG 谱正常的患者（16%[31 名患者中的 5 名]与 0%[21 名患者中的 0 名]；p=0.05）。没有 TEG 谱正常的患者出现有症状的 VTE。
接受手术的肌肉骨骼肿瘤患者存在高凝状态，这可通过 TEG 检测确定。年龄较大、女性和患有软组织疾病（而不是骨疾病）的患者在我们的队列中更有可能表现出 TEG 定义的高凝状态。术前 TEG 定义的高凝状态患者的术后 VTE 发生率较高。这项试点研究的结果值得进一步研究，也许可以通过多中心合作提供足够的队列来支持强大的多变量分析，更好地描述高凝状态的患者和疾病风险因素。TEG 定义的高凝状态患者可能需要更高的 VTE 警惕性，并仔细考虑其化学预防方案。未来的工作还可以评估 TEG 指导的化学预防的有效性，因为该检测结果可以为选择抗血小板剂还是抗凝剂提供信息。
III 级，治疗性研究。
