title: 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.
authors.forename: Julia
authors.initials: J
authors.lastname: Riedl
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kaider
authors.forename: Christine
authors.initials: C
authors.lastname: Marosi
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Prager
authors.forename: Beate
authors.initials: B
authors.lastname: Eichelberger
authors.forename: Alice
authors.initials: A
authors.lastname: Assinger
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pabinger
authors.forename: Simon
authors.initials: S
authors.lastname: Panzer
authors.affiliation: Cihan Ay, MD, Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria, Tel.: +43 1 40400 44100, Fax: +43 1 40400 40300, E-mail: cihan.ay@meduniwien.ac.at.
authors.forename: Cihan
authors.initials: C
authors.lastname: Ay
mesh_terms: D000328:Adult; D000368:Aged; D001317:Austria; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D054556:Venous Thromboembolism / Q000097:blood* / Q000175:diagnosis / Q000401:mortality
chemical_list: D015415:Biomarkers; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C546937:SELP protein, human
keywords: Platelets; cancer; monocyte-platelet aggregates; mortality; thrombosis