Extracellular vesicles in thrombogenesis and VTE

Extracellular vesicles (EVs) are small (50 -1000 nm) bilayer-membrane coated particles released from cells upon activation and are characterized by their size and cell of origin. EVs have procoagulant properties presumably due to expression of negatively charged phospholipids on the external membrane and tissue factor  under certain pathophysiological conditions (e.g. cancer and acute infections). 

The overall aim of this project is to identify specific EV profiles with distinct procoagulant properties associated with VTE risk that could improve risk assessment and be targetable for interventions. We will establish state-of-the-art methodologies for EV measurements in house and optimize preanalytical conditions. We will develop new methods to assess the procoagulant properties and role of EVs for VTE risk. These methods include (i) specific assays suitable for measurement of the expression of EV-specific procoagulant phospholipids in plasma, (ii) measurement of tissue factor activity in a milieu abundant of negatively charged phospholipids, (ii) a bead-based assay for direct semi-quantitative measurement of cell-specific EVs in plasma, (iv) a method for assessment of the biochemical composition of single EVs (Raman Tweezers Microspectrometry), and (v) proteomics of EVs isolated from specific cells.

Principal Investigator: John-Bjarne Hansen

External collaborators: Olav Gaute Hellesø, Balpreet Singh Ahluwalia (Department of Physics and Technology, UiT)

Publications:

Guerreiro et al. Extracellular vesicles from activated platelets possess a phospholipid-rich biomolecular profile and enhance prothrombinase activity. J Thromb Haemost. 2024.

Osterud et al. A rapid, sensitive, and specific assay to measure TF activity based on chromogenic determination of thrombin generation. J Thromb Haemost. 2022;20:866-76.

Ramberg et al. Rosuvastatin treatment decreases plasma procoagulant phospholipid activity after a VTE: A randomized controlled trial. J Thromb Haemost. 2022;20:877-87.

Snir et al. Plasma levels of platelet-derived microvesicles are associated with risk of future venous thromboembolism. J Thromb Haemost. 2022;20:899-908.

Touw et al. Effect of lower-leg trauma and knee arthroscopy on procoagulant phospholipid-dependent activity. Res Pract Thromb Haemost. 2022;6:e12729.

Ramberg et al. Plasma procoagulant phospholipid clotting time and venous thromboembolism risk. Res Pract Thromb Haemost. 2021;5:e12640.

Ramberg et al. A modified clot-based assay to measure negatively charged procoagulant phospholipids. Sci Rep. 2021;11:9341.

Jamaly et al. Elevated plasma levels of P-selectin glycoprotein ligand-1-positive microvesicles in patients with unprovoked venous thromboembolism. J Thromb Haemost. 2018.

Jamaly et al. Impact of preanalytical conditions on plasma concentration and size distribution of extracellular vesicles using Nanoparticle Tracking Analysis. Sci Rep. 2018;8:17216.

Basavaraj et al. Differential ability of tissue factor antibody clones on detection of tissue factor in blood cells and microparticles. Thromb Res. 2012;130:538-46.

Nasjonalforeningen for folkehelsen (Post Doctor grant for E. Guerreiro)

Stiftelsen K.G. Jebsen