Abstract
Patients with glioblastoma multiforme (GBM) suffer from an increased incidence of vascular thrombotic events. However, key influencing factors of the primary hemostasis have not been characterized in GBM patients to date. Thus, the present study determines the activation level of circulating platelets in GBM patients, in-vitro reactivity to agonist-induced platelet stimulation and the formation of circulating platelet-leucocyte conjugates as well as the plasma levels of the proinflammatory lipid mediator sphingosine-1-phosphate (S1P). The endogenous thrombin potential (ETP) was determined as global marker for hemostasis.The 21 GBM patients and 21 gender and age matched healthy individuals enrolled in this study did not differ in mean total platelet count. Basal surface expression of platelet CD63 determined by flow cytometry was significantly increased in GBM patients compared to controls as was observed for the concentration of soluble P-selectin in the plasma of GBM patients. While the ETP was not affected, the immunomodulatory lipid S1P was significantly decreased in peripheral blood in GBM. Interestingly, monocyte expression of PSGL-1 (CD162) was decreased in GBM patient blood, possibly explaining the rather decreased formation of platelet-monocyte conjugates.Our study reveals an increased CD63 expression and P-selectin expression/ secretion of circulating platelets in GBM patients. In parallel a down-modulated PSGL-1 expression in circulating monocytes and a trend towards a decreased formation of heterotypic platelet-monocyte conjugates in GBM patients was seen. Whether this and the observed decreased plasma level of the immunomodulatory S1P reflects a systemic anti-inflammatory status needs to be addressed in future studies.
Highlights
The glioblastoma multiforme (GBM) is the most common primary brain tumor in adult patients [1]
Platelet count did not differ in both groups (GBM: 257 Gpt/l, range from 135 to 383; CON: 245 Gpt/ l, range from 169 to 375), but the GBM-group had a higher total leucocyte blood count
The present study indicates for the first time an increased expression of platelet surface CD63 and soluble
Summary
The glioblastoma multiforme (GBM) is the most common primary brain tumor in adult patients [1]. The role of the primary hemostasis, i.e. the activation status of circulation platelets is less clear. Platelets are the main player of the primary haemostasis, but interact with the immune system . This is reflected by the secretion of immunomodulatory mediators, and involves formation of heterotypic conjugates between platelets and leucocytes. The formation of such circulating platelet-immune cell conjugates is considered as a surrogate of inflammatory responses and is well described in diseases such as sepsis and atherosclerosis [13,14,15,16]. After in vivo or ex vivo platelet activation, the formation of platelet-leucocyte conjugates (PLC) is typically elevated [10, 16]
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