Platelet Activation And Heterotypic Platelet Leukocyte Conjugate Formation In The Blood Of Glioblastoma Patients

Objective Glioblastoma patients (GBM) suffer from an increased incidence of cardiovascular events. Platelets are well known as main player of the primary hemostasis, but have a broad range of additional functions. The formation of heterotypic conjugates between platelets and leukocytes (PLC) represents a pro-inflammatory surrogate marker and is usually increased after platelet activation. The aim of the present study was to evaluate the platelet activation status and the rate of circulating PLC in GBM. Methods Blood samples were drawn of consecutive patients before surgery for a suspected glioblastoma. The formation of PLC and several parameters of platelet activation were determined by flow cytometry before and after stimulation with either ADP or the thrombin receptor-activating peptide (TRAP) in vitro: expression of P-Selectin, CD63, CD40L and fibrinogen-binding to the activated GPIIb/ IIIa. Blood samples from age and gender matched healthy volunteers were used as controls. Statistical analysis was done with the Mann-Whitney-Test. Results Final analysis included 22 patients with histopathological proven virgin glioblastoma (9f, 13m, mean age 67.5 years, range from 55 to 86 years) and their respective controls. Basal platelet activation and in vitro platelet reactivity was increased in GBM. The difference got significant in the basal expression of CD63 (2.8% versus 1.9%, p=0.008), the Fibrinogen-binding after ADP-stimulation (110.3 MFI versus 63.1 MFI, p=0.04) and the CD63 expression after TRAP-stimulation (38.4% versus 33.3%, p=0.04). Furthermore, a reduced number of circulating PLC and in vitro PLC formation was seen in GBM without getting statistically significant. Conclusions In this preliminary report, we show for the first time an increased level of platelet activation and agonist-induced platelet reactivity in GBM. Both could be a reflection of the pro-thrombotic status in these patients. Interestingly, the formation of PLC was not increased, but in tendency decreased. Whether this observation potentially mirrors the intratumoral, anti-inflammatory microenviroment in GBM remains unclear. Citation Format: Sascha Marx, Maximilian Splittstohser, Heiko Paland, Carolin Seifert, Madlen Juettner, Andreas Boehm, Christoph A. Ritter, Sandra Bien-Moeller, Henry W. Schroeder, Bernhard Rauch. Platelet activation and heterotypic platelet leukocyte conjugate formation in the blood of glioblastoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1738. doi:10.1158/1538-7445.AM2017-1738