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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

Julia Riedl
1   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Austria
*   Comprehensive Cancer Centre Vienna, Austria
,
Alexandra Kaider
2   Centre for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Austria
,
Christine Marosi
3   Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Austria
*   Comprehensive Cancer Centre Vienna, Austria
,
Gerald W. Prager
3   Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Austria
*   Comprehensive Cancer Centre Vienna, Austria
,
Beate Eichelberger
4   Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Austria
,
Alice Assinger
5   Centre for Physiology and Pharmacology, Medical University of Vienna, Austria
,
Ingrid Pabinger
1   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Austria
*   Comprehensive Cancer Centre Vienna, Austria
,
Simon Panzer   #
4   Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Austria
,
Cihan Ay   #
1   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Austria
6   Department 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
› Author Affiliations Financial support: This study was supported by funds of the Austrian National Bank (Anniversary Fund; project number 14744), Funds of the Mayor of Vienna (Bürgermeister-Fonds; project number 14056) and by the Austrian Science Fund (FWF), Special Research Program (SFB) 54.
Further Information

Publication History

Received: 15 February 2016

Accepted after major revision: 09 September 2016

Publication Date:
14 November 2017 (online)

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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

# These authors share senior authorship.


 

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