PB0734 - Platelet Procoagulant Potential Increases Following Thromboprophylaxis Completion in Patients with Primary Breast Cancer and Surgically Treated Metastatic Bone Disease

Background: For individuals with breast cancer, bone is a common secondary site of spread, leading to metastatic bone disease (MBD) and increased fracture risk. Those with breast cancer are at up to 4-fold increased risk of venous thromboembolism (VTE) compared to age-matched females without cancer. Current thromboprophylaxis guidelines following orthopaedic surgery do not consider increased cancer-associated VTE risk, and the platelet contribution to thrombosis is poorly understood. Examining the spatiotemporal morphological changes that platelets undergo (i.e., procoagulant membrane dynamics, PMD) can address this knowledge gap by providing mechanistic insights into post-operative hypercoagulability.

Aims: To use a systematic and iterative approach to examine platelet PMD in patients with primary breast cancer and surgically treated MBD.

Methods: Consecutive adults with primary breast cancer and MBD undergoing orthopaedic surgery for pathologic fracture treatment were enrolled into this single-centre, prospective cohort study (HREBA.CC-20-0147). After obtaining informed consent, serial blood samples for PMD analysis were collected over a 6-month post-operative period. Platelets in plasma, reconstituted to contain leukocytes, were visualized using high-resolution fluorescence microscopy, followed by a systematic analysis of PMD. Findings were coupled with biochemical and proteomic analyses. Data were tested for normality using the Shapiro-Wilk test and presented as box-and-whisker plots (p < 0.05).

Results: Platelet procoagulant potential was characterized in the nine patients (61 ± 11 years) who completed the study. All patients received post-operative thromboprophylaxis (4500 units of low-molecular-weight heparin, LMWH) taken daily for 32 ± 5 days. A prothrombotic state was sustained for up to five months after thromboprophylaxis was discontinued. This was associated with spleen tyrosine kinase (SYK) activation and increased homotypic and heterotypic platelet microaggregates.

Conclusion(s): Analysis of platelet PMD identified a platelet-based mechanism underlying the prothrombo-inflammatory state, recalcitrant to thromboprophylaxis. Further investigation into these mechanisms may elucidate novel drug targets for effective VTE prophylaxis.