Abstract 1122
Background
Platelet activation by tumour cells contributes to critical steps in the formation of metastases. Mechanisms include protection of tumour cells from immune destruction, interaction of platelet receptors with tumour ligands to facilitate adhesion, and enrichment of the tumour microenvironment to promote extravasation and proliferation. This study investigated the differences in platelet activation markers in cancer patients compared to healthy donors, and the effect of the addition of in vitro antiplatelet agents.
Methods
Blood was collected from consented healthy volunteers and patients with metastatic cancer. Platelet rich plasma was prepared. Light transmission aggregometry measured spontaneous aggregation of platelet samples, without the addition of exogenous agonists. Flow cytometry measured the platelet activation markers P-selectin and fibrinogen binding on unstimulated, untreated platelets, and on unstimulated platelets incubated with aspirin, Ticagrelor and dual antiplatelet therapy.
Results
62 cancer patients and 17 healthy donors provided blood samples. There was increased spontaneous aggregation of platelets from cancer patients compared to healthy platelets (9±1.1% vs 4±0.9% p = 0.02). Platelets from cancer patients had increased basal levels of P-selectin expression compared to healthy platelets (17.2±2.7% vs 8.4±0.3%) and incubation of platelets with antiplatelets had no effect. There was no difference in the basal level of fibrinogen binding between populations, however incubation with dual antiplatelet therapy reduced baseline fibrinogen binding in platelets from cancer patients (3.1±0.7% vs 10.8±3.7%).
Conclusions
Platelets from cancer patients are hyperactive and easily form aggregates compared to healthy platelets. Platelets from cancer patients have higher levels of the activation marker P-selectin. Aggregation requires fibrinogen binding and incubation with dual antiplatelet therapy reduces this binding in platelets from cancer patients. The interaction between tumour cells and platelets could be a potential biomarker of disease, and this is reduced by antiplatelet drugs. Further studies determining the effect of in vivo antiplatelet therapy on platelets in cancer patients are being undertaken.
Clinical trial identification
EudraCT: 2014‐004049‐29; Start date: 10‐03‐2015.
Editorial acknowledgement
Legal entity responsible for the study
University of Leicester.
Funding
AstraZeneca.
Disclosure
A. Thomas: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. A. Goodall: Research grant / Funding (institution): Hoffmann La Roche; Research grant / Funding (institution): AstraZeneca. D. Adlam: Research grant / Funding (institution): Abbott Vascular Inc; Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.
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