Dissertation committee:
Τσαντές Ε. Αργύριος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Παπαγγελόπουλος Παναγιώτης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κουλουβάρης Παναγιώτης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Βαλσάμη Σερένα, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Γιαλεράκη Αργυρή, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Κοκόρη Στυλιανή, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Κριεμπάρδης Αναστάσιος, Καθηγητής, Πανεπιστήμιο Δυτικής Αττικής
Summary:
Introduction : Surgical resection of malignant bone tumors is associated with a high risk of venous thromboembolism (VTE) due to the presence of multiple risk factors of Virchow triad in this particular group of patients. Patients who undergo major surgical intervention for bone tumors are at a significantly increased thrombotic risk due to the activation of the coagulation system. The risk of a clinically significant VTE is two times higher in surgical oncologic patients compared to the general population without thrombophylactic measures. Conventional laboratory coagulation tests can evaluate only a specific phase of coagulation. On the other hand, viscoelastic methods such as a ROTEM have the advantage of an overall assessment of the formation and breakdown of the thrombus through a dynamic analysis of all phases of coagulation. Therefore, viscoelastic rotational thromboelastometry can provide a detailed evaluation of the hemostatic derangements that occur in patients with bone tumors and may allow for more effective and individualized thromboprophylactic measures following oncologic orthopedic surgery.
Purpose: The purpose of this study was to investigate the hemostatic changes caused by bone malignancies by comparing the ROTEM and other conventional coagulation parameters between patients with bone tumors and healthy adults. Moreover , we aimed to evaluate the postoperative changes in the hemostatic profile of patients with bone tumors who undergo surgery by comparing the preoperative and postoperative ROTEM parameters, to evaluate whether the results of ROTEM parameters are associated with the development of symptomatic VTE events following oncologic surgical resection of malignant bone tumors and to evaluate the predictive power of these parameters to identify the hypercoagulable state that is associated with development of symptomatic VTE events following these surgeries.
Methods: For the evaluation of the changes in the hemostatic profile of patients with bone tumors and for the evaluation of the postoperative changes in the hemostatic profile of patients with bone tumors undergoing surgery, 50 patients with bone tumors who underwent tumor resection procedures were included. A matched group for age and gender was also included in the study as a control group (20 patients), consisting of healthy adults who underwent minor orthopedic surgeries at the same hospital. Laboratory testing was performed preoperatively in healthy adults to assess their baseline hemostatic profile, while in patients with bone tumors, laboratory testing was performed at 2 perioperative time points, before surgery to assess their baseline hemostatic profile and on the 2nd postoperative day to assess the postoperative hemostatic profile of these patients, under thromboprophylaxis. Demographics, conventional laboratory assays and ROTEM parameters were recorded and compared between patients and healthy adults. In order to evaluate the association of ROTEM parameters with the development of symptomatic VTE events following oncologic surgical resection of malignant bone tumors and for the estimation of the predictive power of these parameters to identify the hypercoagulable state that is associated with development of symptomatic VTE events, 113 patients were included. The demographics and certain tumor characteristics such as the histologic type and location were recorded. Patients were monitored clinically during their hospital stay for the development of symptoms indicative for deep vein thrombosis (DVT) or pulmonary embolism (PE). Following hospital discharge, all patients were followed up at 1 and 3 months postoperatively for the development of any VTE events. A ROTEM analysis was performed in all patients at the time of their admission to the hospital and on the second postoperative day. The collected demographic data, conventional laboratory test and ROTEM parameters were compared between patients with and without symptomatic VTE.
Results: In the part of the study regarding the evaluation of the changes in the hemostatic profile of patients with bone tumors, the conventional coagulation tests were comparable between the patient group and healthy adults. However, the preoperative ROTEM parameters of the patients significantly differed from those of the healthy adults, indicating a hypercoagulable state in the patients with bone tumors. Specifically, compared to the healthy adults, the tumor patients had a significantly lower EXTEM and INTEM CT, a lower EXTEM and INTEM CFT , a higher EXTEM and INTEM A10 , a higher EXTEM and INTEM MCF, a higher EXTEM and INTEM alpha angle and a higher EXTEM and INTEM LI60 .
The comparison between the preoperative and postoperative ROTEM parameters in the patients with bone tumors revealed that surgery resulted in an even higher coagulation potential, since the postoperative CT was lower than the preoperative CT, the postoperative CFT was lower than the preoperative CFT, the postoperative A10 was higher than the preoperative A10 , and the postoperative MCF was higher than the preoperative MCF. Another interesting finding of our study was that metastatic bone disease was associated with a more hypercoagulable profile, based on the ROTEM parameters, than the primary bone tumors, probably due to the systemic spread of malignant cells. Specifically, the patients with metastatic bone disease had a higher EXTEM and INTEM A10 and a higher EXTEM and INTEM MCF compared to the patients with primary bone tumors, suggesting a higher clot strength in metastatic bone disease. Last, an INTEM LI60 value indicative of fbrinolysis shutdown (≥98%) had the best prognostic capacity for the development of VTE events.
Conclusion: According to the findings of this study, ROTEM analysis demonstrated a high predictive accuracy in detecting the level of hypercoagulability that is associated with symptomatic VTE. Rotational thromboelastometry can provide a detailed insight into the hemostatic derangements that occur in patients with bone tumors and a detection of other pathological derangement of the main mechanisms involved in MAC, such as fibrinolysis inhibition. D-dimer levels are commonly used to diagnose or rule out VTE, and LI60 could also be valuable in this setting. Using both fbrinolysis shutdown, as refected by ROTEM LI60, and high D-dimer levels may contribute to the identifcation of patients at high-risk of postoperative VTE and the implementation of individualized strategies in thromboprophylaxis.
Keywords:
Thromboembolism,Malignant bone tumors ,Viscoelastic methods ,Thromboelastometry,Hemostasis
