Dynamic platelet function is markedly different in patients with cancer compared to healthy donors

Abstract

Despite a fivefold increased risk of thromboembolism in patients with cancer, the mechanism of arterial thromboembolism is poorly understood. To address this, we investigated platelet function in cancer patients and healthy controls using an assay that mimics the arterial vasculature. Blood samples from cancer patients (n = 36) and healthy controls (n = 22) were perfused through custom-made parallel-plate flow chambers coated with von Willebrand factor (VWF) under arterial shear (1,500 s−1). Multiparameter measurements of platelet interactions with the immobilized VWF surface were recorded by digital-image microscopy and analyzed using custom-designed platelet-tracking software. Six measured parameters that characterize in detail the surface motion and surface binding of several hundred platelets per blood sample differed significantly in those with cancer from the healthy donors. In particular, it was found that patients with cancer had decreased numbers of platelets interacting, translocating and adhering to VWF. There were also reductions in the speed and distances that platelets traveled on VWF in comparison to healthy controls. Platelet function differed between those with early-stage cancer compared to those with later stage cancer. Patients with advanced cancer had an increased number of platelets stably adhering to VWF and greater platelet surface coverage after a given time of interaction. To the best of our knowledge, our results demonstrate for the first time that dynamic platelet function is markedly different in patients with cancer compared to healthy donors.

Keywords

• blood platelets
• cancer
• platelet function tests
• von willebrand factor