VPB0760 - Heightened Procoagulation After Thromboprophylaxis Completion inOrthopaedic Surgery Patients with Metastatic Bone Disease: Outcome of A Pilot Study

Background: Patients with metastatic bone disease (MBD) often require surgical stabilization of painful or unstable bone lesions. Hypercoagulability is associated with malignancy, and venous thromboembolism risk is 7-fold higher in patients with MBD. Platelet-tumour cell interactions can promote metastasis, and platelets’ role in the hypercoagulability after surgical intervention for MBD is ill-defined.

Aims: To characterise platelet activation and procoagulation mechanisms in patients with MBD before and after surgical interventions.

Methods: Healthy participants and patients with various primary cancers (lung, breast, pancreatic, renal, multiple myeloma, and colorectal) provided informed consent (n=8; 67±9years; HREBA.CC-20-0147). We examined patients’ blood at 7-timepoints (pre-operatively; and postoperative days 1, 3, 5, 14, 42, and 90). We utilized high-resolution fluorescence imaging to visualize platelets in plasma reconstituted to contain leucocytes, followed by a systematic analysis of procoagulant membrane dynamics. We then coupled our findings to biochemical and proteomics studies in these patients.

Results: Platelet activation and membrane P-selectin expression increased 1- to 2-fold after completion of thromboprophylaxis or VTE treatment in all patients except for our myeloma patient, in which platelet activation increased dramatically post-operatively, but normalized after thromboprophylaxis completion. Expectedly, platelet membrane phosphatidylserine externalization and thrombin generation followed a similar temporal pattern. We visualized microthrombi (aggregate of ≥5 platelets) and platelet-leucocyte aggregate in the fresh plasma from all patients, but not healthy participants. Both aggregates increased rapidly after the complexion of thromboprophylaxis or the discontinuation of VTE treatment in patients with solid primary cancers in particular. We associated the amplified procoagulation with increased phosphorylation of spleen tyrosine kinase (Syk:Tyr-525/Tyr-526) in platelets, and a plasma milieu enriched with vWF, FAM65B, and the Afamin-AFM and Attractin-ATRN inflammatory mediators.

Conclusion(s): Procoagulation continued beyond the duration of thromboprophylaxis’ in surgical patients with MBD. On-going study will provide further mechanistic insight into hypercoagulability and aims to identify novel drug targets for effective thromboprophylaxis in MBD patients.