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

Julia Riedl; Alexandra Kaider; Christine Marosi; Gerald W. Prager; Beate Eichelberger; Alice Assinger; Ingrid Pabinger; Simon Panzer; Cihan Ay

doi:10.1160/TH16-02-0123

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2017; 117(01): 90-98
DOI: 10.1160/TH16-02-0123

Cellular Haemostasis and Platelets

Schattauer GmbH

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

Authors

Julia Riedl

¹Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Austria

^*Comprehensive Cancer Centre Vienna, Austria
Alexandra Kaider

²Centre for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Austria
Christine Marosi

³Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Austria

^*Comprehensive Cancer Centre Vienna, Austria
Gerald W. Prager

³Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Austria

^*Comprehensive Cancer Centre Vienna, Austria
Beate Eichelberger

⁴Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Austria
Alice Assinger

⁵Centre for Physiology and Pharmacology, Medical University of Vienna, Austria
Ingrid Pabinger

¹Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Austria

^*Comprehensive Cancer Centre Vienna, Austria
Simon Panzer^#

⁴Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Austria
Cihan Ay^#

¹Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Austria

⁶Department of Medicine, Thrombosis and Hemostasis Program, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

^*Comprehensive Cancer Centre Vienna, Austria

Abstract

Summary

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.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Platelets - thrombosis - monocyte-platelet aggregates - cancer - mortality

Full Text

References

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Supplementary Material

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