Procoagulant activity in high grade serous ovarian cancer patients following neoadjuvant chemotherapy-The role of the activated protein C pathway

Abstract

Introduction: Ovarian cancer patients are at high risk of thrombosis particularly during chemotherapy treatment however the mechanism is not understood. The aim of this study is to investigate the role of the activated protein C (aPC) pathway in the procoagulant activity observed in ovarian cancer patients undergoing neoadjuvant chemotherapy. Patients and methods: Thrombin generation was determined before and after addition of thrombomodulin (TM) in high grade serous ovarian cancer (HGSOC) patients treated with neoadjuvant chemotherapy (n = 29) compared with HGSOC patients who were chemo naïve (n = 23) and patients with benign tumours (n = 29). Plasma expression of proteins from the aPC pathway was analysed. mRNA expression was determined in endothelial (EA.hy926) and ovarian (OAW42) cell lines following addition of carboplatin and paclitaxel. Results: Lower levels of ETP (p < 0.007; p < 0.003) and peak thrombin (p < 0.0008; p < 0.0018) were found in the neoadjuvant group compared with both chemo naïve and benign groups. Following addition of TM, ETP (p < 0.0005) and peak thrombin (p < 0.0049) were higher in the neoadjuvant group compared with the benign controls indicating an increase in aPC resistance. Increased TM and lower levels of protein S were found in the neoadjuvant group compared with benign controls (p < 0.05; p < 0.003). Factor V levels were increased in the neoadjuvant group compared with the chemo naïve group (p < 0.05). Carboplatin and paclitaxel altered the expression of EPCR and thrombomodulin in OAW42 cells with a modest effect on EA.hy926 cells. Conclusion: Chemotherapy induced procoagulant activity in HGSOC is associated with an alteration in expression of key members of the aPC pathway. This acquired aPC resistance may explain the procoagulant phenotype associated with ovarian cancer patients undergoing chemotherapy.

Venous thromboembolism in women with ovarian cancer undergoing neoadjuvant chemotherapy prior to cytoreductive surgery: A retrospective study

“…9,23 In addition, NACT can lead to VTE via pathways including reduced protein C and S expression (from reduced vitamin K absorption), increased factor V expression, and direct injury to vascular endothelium. 24,25 In our study, clear cell and carcinosarcomas were associated with VTE, although the numbers are small and do not reach statistical significance in the case of clear cell disease. This reflects their at least 2.5-fold greater VTE risk, which is known from larger studies, 23,26 most likely because of increased ectopic production of tissue factor and factor VII.…”

Effects of Laparoscopic Hyperthermic Perfusion Therapy Combined with Adjuvant Treatment of Compound Yew Capsule on Ovarian Blood Flow Parameters and Immune Function in Patients with Ovarian Cancer

“…Some scholars believe its etiology is associated with endocrine and fertility factors. If not appropriately diagnosed early, ovarian cancer can be life-threatening and more challenging to treat at later stages [ 4 , 6 ]. Previously, traditional Chinese medicine (TCM) has been extensively applied as a promising adjunctive drug in the fight against ovarian cancer [ 7 , 8 ].…”