Journal

Journal of Thrombosis and Haemostasis

Papers (3)

Risk of venous thromboembolism and bleeding after major surgery for ovarian cancer: standard in-hospital versus extended duration of thromboprophylaxis

Venous thromboembolism (VTE) is a frequent complication in patients with ovarian cancer after major surgery. Based on limited data, international guidelines recommend extended thromboprophylaxis for up to 28 days. To assess the incidence of VTE and bleeding within 30 days following major surgery in patients with ovarian cancer and to evaluate the association between VTE and thromboprophylaxis duration. This was a single-center, retrospective, "before-after" cohort study in patients with ovarian cancer undergoing major surgery. Before July 2019, the local protocol mandated a standard course of thromboprophylaxis during hospital stay only. From July 2019 onward, patients received extended thromboprophylaxis for 28 days. The cumulative incidences of VTE and major bleeding within 30 days after surgery were estimated using the Kaplan-Meier method, with 95% confidence intervals (CIs). Cox regression analysis was performed to evaluate the association between thromboprophylaxis duration and VTE incidence. Between January 2018 and December 2020, 250 women were included, of which 118 (47.2%) received extended and 132 (52.8%) standard thromboprophylaxis. During follow-up, 12 patients developed VTE (cumulative incidence, 4.8%; 95% CI, 2.1-7.4) and 2 major bleeding (cumulative incidence 0.8%; 95% CI, 0.0-1.9). Compared with standard thromboprophylaxis, VTE incidence was numerically lower with extended duration of thromboprophylaxis (5/118 [4.2%] vs 7/132 [5.3%]) but not significantly different (hazard ratio, 0.80; 95% CI, 0.25-2.52). The risk of major bleeding was similar in both groups (1/118 [0.8%] vs 1/132 [0.8%]; hazard ratio, 1.12; 95% CI, 0.07-17.89). The cumulative VTE incidence in patients with ovarian cancer following major surgery was considerable. Extended thromboprophylaxis was safe and associated with a numerically lower risk of VTE but not significantly different.

Podoplanin promotes tumor growth, platelet aggregation, and venous thrombosis in murine models of ovarian cancer

Podoplanin (PDPN) is a sialylated membrane glycoprotein that binds to C-type lectin-like receptor 2 on platelets resulting in platelet activation. PDPN is expressed on lymphatic endothelial cells, perivascular fibroblasts/pericytes, cancer cells, cancer-associated fibroblasts, and tumor stromal cells. PDPN's expression on malignant epithelial cells plays a role in metastasis. Furthermore, the expression of PDPN in brain tumors (high-grade gliomas) was found to correlate with an increased risk of venous thrombosis. We examined the expression of PDPN and its role in tumor progression and venous thrombosis in ovarian cancer. We used mouse models of ovarian cancer and venous thrombosis. Ovarian cancer cells express PDPN and release PDPN-rich extracellular vesicles (EVs), and cisplatin and topotecan (chemotherapies commonly used in ovarian cancer) increase the expression of podoplanin in cancer cells. The expression of PDPN in ovarian cancer cells promotes tumor growth in a murine model of ovarian cancer and that knockdown of PDPN gene expression results in smaller primary tumors. Both PDPN-expressing ovarian cancer cells and their EVs cause platelet aggregation. In a mouse model of venous thrombosis, PDPN-expressing EVs released from HeyA8 ovarian cancer cells produce more frequent thrombosis than PDPN-negative EVs derived from PDPN-knockdown HeyA8 cells. Blood clots induced by PDPN-positive EVs contain more platelets than those in blood clots induced by PDPN-negative EVs. In summary, our findings demonstrate that the expression of PDPN by ovarian cancer cells promotes tumor growth and venous thrombosis in mice.

Publisher

Elsevier BV

ISSN

1538-7836

Journal of Thrombosis and Haemostasis