Heightened Procoagulation After Post-operative Thromboprophylaxis Completion in Colorectal Cancer Patients with Metastatic Bone Disease

ABSTRACT: Platelets play a pivotal role in venous thromboembolism (VTE) and in mediating colorectal cancer (CRC) progression. Still, platelets’ role in the hypercoagulability after surgical intervention for metastatic bone diseases (MBD) is ill-defined. Here, we utilised a high-resolution imaging approach to temporally examine platelet procoagulant membrane dynamics (PMD) in four CRC patients with MBD (CRC/MBD), before and after surgical intervention, over a 6-month period. We coupled this investigation with thrombelastography, quantitative plasma shot-gun proteomics and biochemical analysis. The plasma of CRC/MBD patients was enriched in ADAM1a, ADAMTS7 and physiological ligands for platelet glycoprotein-VI (GPVI/Syk) activation. Thromboprophylaxis attenuated procoagulation from post-operative day-1 (POD1), however, all patients experienced rebound procoagulation on POD3 or POD5, which was associated with a VTE event in two patients. Plasma levels of DNA-histone complexes increased steadily after surgery and throughout the study period. Also, we increasingly sighted both homotypic and heterotypic platelet microaggregates after surgery in CRC/MBD but not healthy control participants plasma. Together, our data elucidates the cell biology of a prothrombo-inflammatory state caused by disease and vascular injury, and recalcitrant to thromboprophylaxis. New mechanistic insights into hypercoagulability in CRC/MBD patients may identify novel drug targets for effective thromboprophylaxis type and duration after orthopaedic surgery.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Platelet, Blood Serum

SUBMITTER: Luiz Gustavo de Almeida  

LAB HEAD: Antoine Dufour

PROVIDER: PXD034160 | Pride | 2023-02-23

REPOSITORIES: Pride