Decreased platelet reactivity in patients with cancer is associated with high risk of venous thromboembolism and poor prognosis

Abstract

Platelets are suggested to play a crucial role in cancer progression and the prothrombotic state of cancer patients. Here, we aimed to examine the activation status of platelets in cancer patients and investigate their association with risk of death and occurrence of venous thromboembolism (VTE) in a prospective observational cohort study. We measured platelet surface P-selectin, activated glycoprotein (GP) IIb/IIIa and monocyte-platelet aggregate (MPA) formation in vivo and platelet response to ex vivo stimulation with agonists of protease-activated receptor (PAR) -1, -4, and GPVI, by whole blood flow cytometry, before beginning of chemotherapy and repeatedly during the first six months thereafter (total number of samples analysed: 230). Endpoints of the study were occurrence of death or VTE during a two-year follow-up, respectively. Of 62 patients (median age [interquartile range, IQR]: 63 [54-70] years, 48 % female), 32 (51.6 %) died and nine (14.5 %) developed VTE. Association with a higher risk of death was found for lower platelet surface expression of P-selectin and activated GPIIb/IIIa in vivo and in response to PAR-1, -4 and GPVI activation, but not for MPA formation. Furthermore, reduced platelet responsiveness to PAR-1 and GPVI agonists was associated with higher risk of VTE (hazard ratio per decile increase of percentage P-selectin positive platelets: 0.73 [0.56-0.92, p=0.007] and 0.77 [0.59-0.98, p=0.034], respectively). In conclusion, cancer patients with a poor prognosis showed decreased platelet reactivity, presumably as a consequence of continuous activation. Our data suggest that decreased platelet reactivity is associated with increased mortality and VTE in cancer.

Association of Platelet Count and Mean Platelet Volume with Overall Survival in Patients with Cirrhosis and Unresectable Hepatocellular Carcinoma

“…While previous studies in non-cancer patients suggested that larger thrombocytes are functionally more active and elevated MPV was associated with various thrombotic events and a worse outcome [46,47], a higher MPV was associated with a significantly increased survival in patients with various solid tumors [29]. In this context, low MPV may reflect degranulated "exhausted" platelets that have already secreted their potentially tumor growth-promoting cytokines, and thus are associated with a worse outcome in cancer patients [48,49].…”

Impaired mitochondrial activity explains platelet dysfunction in thrombocytopenic cancer patients undergoing chemotherapy

“…32 Exhausted platelets were characterized by a high integrin activation and P-selectin expression in the absence of stimulating agents, and a reduced increase in the parameters after agonist stimulation. These changes might point to platelet activation in vivo , resulting in a secondary loss of function.…”

Preoperative plateletcrit is a Prognostic Biomarker for Survival in Patients with Non-Small Cell Lung Cancer

“…Experimental evidence suggests that platelets actively promote cancer progression through a variety of mechanisms, including protecting cancer cells from immune surveillance, negotiating the arrest of cancer cells in the microvasculature, and stimulating angiogenesis [15,21]. Decreased platelet surface expression of P-selectin and activated glycoprotein (GP)IIb/IIIa, in vivo and in response to protease-activated receptor (PAR)-1, PAR-4, and GP VI activation, has been associated with poor OS in patients with cancer [22].…”