A combination of platelet features allows detection of early-stage cancer.

BACKGROUND: Detection of early-stage cancer significantly improves patient survival. As platelets play an important role in cancer progression, we aimed to investigate whether platelets can be used for the discovery of early-stage cancer. METHODS: Patients with lung (n = 86) or head of pancreas (n = 42) cancer were included, as were healthy sex- and age-matched controls (n = 92). Blood was collected before initiation of treatment. Platelet count, volume and activation status were quantified in whole blood. Next, concentrations of vascular endothelial growth factor, platelet-derived growth factor, platelet factor 4, thrombospondin-1 and connective tissue-activating peptide III were measured in both platelets and plasma. Using the results, two multivariable diagnostic models were developed and internally validated. FINDINGS: Multiple platelet features, including platelet count, volume and protein content, were significantly changed in lung and head of pancreas cancer patients. However, the pattern of changes differed between both groups. The diagnostic model developed for lung cancer discriminated very well between patients and controls (AUC = 88.7%). Addition of smoking as a variable significantly increased the AUC of the model to 94.5%. The diagnostic model for head of pancreas cancer also performed well (AUC = 82.7%). Both models were internally validated, resulting in optimism-corrected AUC's of 86.8% and 80.8%, respectively. INTERPRETATION: In patients with lung or head of pancreas cancer, several platelet characteristics are changed compared to healthy sex- and age-matched controls. A cancer type-specific combination of these platelet features can be used to discriminate between patients with early-stage cancer and healthy individuals.

Sunitinib uptake inhibits platelet function in cancer patients.

BACKGROUND: Sunitinib is an oral tyrosine kinase inhibitor used for cancer treatment. Patients treated with sunitinib are at higher bleeding risk. As tyrosine kinases are essential for platelet signalling, the effects of sunitinib on platelet function in vitro and in cancer patients on treatment were investigated. PATIENTS AND METHODS: Blood samples were collected from eight healthy volunteers and eight patients diagnosed with metastatic renal cell cancer (RCC) before and 2 weeks on treatment with sunitinib. Platelets from 15 additional healthy individuals were preincubated with sunitinib or vehicle to perform in vitro experiments. Immunofluorescence imaging, western blotting, light transmission aggregometry, whole blood perfusion over collagen, flow cytometry and ELISA were performed. RESULTS: Confocal microscopy indicated that platelets sequester sunitinib in vitro and in patients. In platelets from healthy controls, tyrosine phosphorylation was inhibited by sunitinib. Also, sunitinib dose dependently reduced collagen- and ADP-induced aggregation, collagen-dependent thrombus formation and collagen-induced secretion of platelet-derived growth factor and ß-thromboglobulin. In blood from RCC patients before treatment, thrombus formation and procoagulant activity under flow were 47% and 80% higher than in healthy controls. After 14 d of sunitinib treatment, platelet count was moderately, but significantly decreased (from 243 to 144 × 10(9)/l). At the same time, collagen-induced platelet aggregation as well as thrombus formation and phosphatidylserine exposure under flow were significantly reduced (by 45%, 16% and 61%, respectively). CONCLUSIONS: Sunitinib uptake by platelets inhibits collagen receptor-induced aggregation and thrombus formation via reduction of protein tyrosine phosphorylation and α-granule secretion. This dysfunction may contribute to the higher bleeding tendency observed in sunitinib-treated patients.