Abstract Number: PB0931
Meeting: ISTH 2022 Congress
Background: Gynaecological cancers patients are at high risk of venous thromboembolism(VTE) however the mechanism by which VTE occurs is not understood and could be tumour or treatment related.
Aims: The aim of this study is to determine the mechanism of hypercoagulability in gynaecological cancer patients and to assess the role of tumour and treatment factors in the enhanced thrombin generation observed in patients who subsequently develop VTE.
Methods: mRNA expression of Prothrombin(F2), Tissue Factor(TF), Tissue Factor Pathway Inhibitor -1(TFPI-1), TFPI-2, endothelial protein C receptor(EPCR), protein S(PS), protein C (PC), thrombomodulin (TM), Factor V (FV) and VIII (FVIII) was measured in tumour biopsies from 26 treatment naïve gynaecological cancer patients who developed VTE compared with matched controls. Plasma levels of FV, F8, TFPI, TM, PS, EPCR were determined by ELISA and were correlated with thrombin generation(ETP) in patients who subsequently developed VTE (VTE group). Ethical approval and informed consent was obtained.
Results: No significant differences in tumour mRNA expression was observed in patients who developed VTE compared with those who remained thrombosis free. In treatment naïve patients, pre-operative ETP and Factor VIII were significantly increased in patients who developed VTE(VTE group) compared with matched controls(Non VTE group)(P < 0.05;P < 0.03). FVIII correlated with peak thrombin levels in the VTE group (r=0.560). In patients treated with neoadjuvant chemotherapy before surgery, TM was reduced in the VTE group compared with the non VTE group(P < 0.03). TM correlated negatively with ETP in the VTE group(r=-4558).
Conclusion(s): Tumour expression of coagulation proteases does not appear to be implicated in VTE in gynaecological cancer patients. FVIII levels contribute to the pro-coagulant activity observed in treatment naive gynaecological cancer patients who develop VTE. Reduced levels of TM may be linked to chemotherapy associated endothelial damage and result in impaired activation of protein C at the endothelial surface resulting in chemotherapy associated VTE.
To cite this abstract in AMA style:Ward M, O'Toole S, Abu Saadeh F, Marchocki Z, Ibrahim E, Martin F, Gleeson N, O'Leary J, Norris L. Mechanisms of cancer associated thrombosis in gynaecological cancer patients-tumour or treatment effect? [abstract]. https://abstracts.isth.org/abstract/mechanisms-of-cancer-associated-thrombosis-in-gynaecological-cancer-patients-tumour-or-treatment-effect/. Accessed October 1, 2023.
« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/mechanisms-of-cancer-associated-thrombosis-in-gynaecological-cancer-patients-tumour-or-treatment-effect/