Direct Oral Anticoagulants Are Comparable to Low Molecular Weight Heparin at Sustaining the Circulating Extracellular Vesicle and Inflammatory Profiles of Cancer Associated Thrombosis Patients: An Observational Pilot Study.

INTRODUCTION: Cancer patients face a 4 to 7-fold higher risk of developing thrombotic events compared to individuals without cancer. This elevated risk is driven by the underlying tumour biology and the effects of cancer treatments, significantly increasing the mortality rates of these patients. While low molecular weight heparin (LMWH) is the gold standard anticoagulation, direct oral anticoagulants (DOACs) are emerging as effective alternatives. Recent clinical evidence indicates reduced recurrent VTE upon DOAC treatment compared to LMWH; however, there is limited understanding of the underlying mechanistic pathways. Of interest, extracellular vesicles (EVs), released from a multitude of cells including platelets and tumour cells, are known as potent intercellular communication mediators, capable of progressing coagulation, thrombosis, as well as tumour growth and metastasis. METHODS: We characterised the extracellular vesicles and inflammatory markers associated with hypercoagulability and thrombosis in cancer-associated thrombosis (CAT) patients, comparing those treated for 8 weeks with DOACs to those receiving LMWH. This pilot observational study recruited 28 CAT patients (21 baseline, 13 treated with DOACs, 8 treated with LMWH; 14 paired) and quantified their circulating, platelet-derived, and endothelial-derived EVs using Nanoparticle Tracking Analysis and flow cytometry. Proteomics was performed on the EV cargo and patient plasma, quantifying the inflammatory profiles of the patients under both treatment arms. RESULTS AND DISCUSSION: We demonstrated that DOAC treatment maintained hypercoagulable and prothrombotic EV profiles similar to LMWH treatment, showing a remarkably stable EV cargo proteome. Inflammatory profiles were also comparable between treatment arms, with a trend toward a DOAC-mediated reduction of circulating cytokines, highlighting potential anti-inflammatory effects. CONCLUSION: This pilot study demonstrates that DOACs sustain the circulating EV and inflammatory profiles to the same extent as LMWH, supporting this clinical shift in anticoagulant treatment in the cancer setting.