Blood clotting activation analysis for preoperative differentiation of benign versus malignant ovarian masses

Abstract

Preoperative evaluation of patients presenting with ovarian masses is challenging, partly due to shortcomings with the commonly used marker, CA-125. Ovarian cancer is associated with systemic coagulation activation. Measurement of D-dimer, serum tissue factor (TF), and the coagulation process as a whole are considered candidates for improving discrimination between benign and malignant ovarian masses. We therefore sought to identify possible benefits by analyzing preoperative coagulation status in conjunction with CA-125 in patients with ovarian masses. Preoperative blood from 95 patients with ovarian masses (75 benign, 20 malignant) and 30 controls was analyzed, prospectively. Thromboelastography served for global hemostatic assessment. Plasma TF antigen and D-dimer were measured by ELISA and microparticle-associated TF activity by thrombin generation assay. TF microparticles were enumerated by flow cytometry. Time to clot formation by thromboelastography was similar between patients having either benign or malignant ovarian tumors. Clot formation rate, clot strength, and coagulation index were significantly increased in patients having malignant versus benign tumors, indicating that thromboelastography differentiated malignant from benign tumors. D-dimer alone differentiated malignant from benign ovarian tumors and also improved differentiation when combined with CA-125. Circulating TF antigen, activity, and TF microparticle numbers, however, failed to differentiate benign from malignant tumors. Significant coagulation activation occurs in women with ovarian malignancies. Plasma D-dimer may help discriminate between patients with benign and malignant tumors. Thromboelastography may also contribute meaningfully when combined with CA-125 in the preoperative evaluation of ovarian masses. Larger studies are needed to assess these possibilities.

An Antibody–Drug Conjugate That Targets Tissue Factor Exhibits Potent Therapeutic Activity against a Broad Range of Solid Tumors

“…Whole blood was incubated with 10 mg/mL lipopolysaccharide (LPS) or PBS without Ca 2þ and Mg 2þ (4 hours, 37 C), followed by incubation with tissue factor HuMab (10 minutes, room temperature). Thromboelastography (TEG) was performed as described (23). In this system, the LPS-induced decrease in clotting lag time (R) represents a measure for tissue factor activity.…”

A risk score for prediction of venous thromboembolism in gynecologic cancer: The Thrombogyn score

“…38 Our group and others have shown that increased thrombin production as measured by the thrombin generation assay is associated with malignancy and is a predictive marker for VTE. 25,38,39,40 The thrombin generation assay has not been universally accepted as a biomarker in clinical settings 41,42 however, a recent thrombin generation standardization study showed that the standard thrombin generation assay provides good reproducibility in hypercoagulable plasma. 43 When D-dimer and ETP are combined with the Thrombogyn score, the predictive ability of the Thrombogyn score was enhanced.…”

“…D‐dimer has been identified as the strongest prognostic biomarker for VTE in patients with cancer compared with previously tested biomarkers 26 . D‐dimer is frequently raised in ovarian cancer and has been proposed as a diagnostic marker useful in triaging patients; hence, the specificity of D‐dimer as a biomarker for VTE in this population is low 38 . Our group and others have shown that increased thrombin production as measured by the thrombin generation assay is associated with malignancy and is a predictive marker for VTE 25,38,39,40 .…”

Comparison of dextran and albumin on blood coagulation in patients undergoing major gynaecological surgery

“…Perioperative TEG hypercoagulation has also been suggested to reflect the degree of malignancy of ovarian masses (Amirkhosravi et al 2013). Dextran has been suggested to reduce thromboembolism in cancer surgery (Foster et al 2017).…”