title: PO-63 - Exhausted platelets in cancer patients with high risk of venous thromboembolism and poor prognosis.
abstract: BACKGROUND
  Platelets play a crucial role in cancer development, progression and metastatic spread of malignancy. In vitro data show that cancer cells have the ability to activate platelets, and clinical studies found increased levels of platelet activation markers in cancer patients. Moreover, platelets are thought to be involved in the development of venous thromboembolism (VTE) in cancer patients, a frequent complication of malignant disease associated with high morbidity and mortality.
  
  
  OBJECTIVE
  In this study, we aimed to examine the activation status of platelets in cancer patients and investigate the association with risk of future venous thromboembolism (VTE) and mortality.
  
  
  METHODS
  In a prospective observational cohort study of cancer patients we measured pre-chemotherapy platelet P-selectin and glycoprotein (GP) IIb/IIIa expression and monocyte-platelet aggregates (MPA) in vivo and in response to ex vivo stimulation of the platelet activation receptors protease-activated receptor (PAR) -1, -4, and GPVI by whole blood flow cytometry. Primary and secondary endpoints of the study were occurrence of objectively confirmed VTE and death during 2-year follow-up, respectively.
  
  
  RESULTS
  Out of 62 patients (median age [interquartile range, IQR]: 63 [54-70] years, 48% female) with cancers of the pancreas (n=19), lung (n=18), brain (n=14), colon (n=8) and stomach (n=3), 9 (14.5%) developed VTE and 32 (51.6%) died. P-selectin, activated GPIIb/IIIa expression and MPA formation did not significantly differ between tumor sites (Kruskal Wallis test). Reduced platelet responsiveness to PAR-1 and GPVI stimulation was associated with a higher risk of VTE (hazard ratio [HR] per decile increase in %P-selectin positive platelets: 0.73 [95% confidence interval: 0.56-0.92, p=0.007] and 0.77 [0.59-0.98, p=0.034], respectively; Table 1). Further, lower platelet P-selectin and activated GPIIb/IIIa expression in vivo and in response to PAR-1, -4 and GPVI stimulation, but not MPA formation, were associated with a higher risk of death (Table 1).
  
  
  CONCLUSIONS
  Cancer patients with a poor prognosis had degranulated platelets, presumably as a consequence of previous activation. Our data suggest that platelets' continuous activation and thus exhaustion is involved in cancer-associated VTE and cancer mortality.
authors.affiliation: Clinical Division of Haematology and Haemostaseology, Department of Medicine I; Comprehensive Cancer Center Vienna; all Medical University of Vienna, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Riedl
authors.affiliation: Center for Medical Statistics, Informatics and Intelligent Systems.
authors.forename: A
authors.initials: A
authors.lastname: Kaider
authors.affiliation: Clinical Division of Oncology, Department of Medicine I; Comprehensive Cancer Center Vienna; all Medical University of Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Marosi
authors.affiliation: Clinical Division of Oncology, Department of Medicine I; Comprehensive Cancer Center Vienna; all Medical University of Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Prager
authors.affiliation: Department of Blood Group Serology and Transfusion Medicine.
authors.forename: B
authors.initials: B
authors.lastname: Eichelberger
authors.affiliation: Clinical Division of Haematology and Haemostaseology, Department of Medicine I; Comprehensive Cancer Center Vienna; all Medical University of Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Koder
authors.affiliation: Department of Blood Group Serology and Transfusion Medicine.
authors.forename: S
authors.initials: S
authors.lastname: Panzer
authors.affiliation: Clinical Division of Haematology and Haemostaseology, Department of Medicine I; Comprehensive Cancer Center Vienna; all Medical University of Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Pabinger
authors.affiliation: Clinical Division of Haematology and Haemostaseology, Department of Medicine I; Comprehensive Cancer Center Vienna; all Medical University of Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Ay