Novel insights into the mechanisms of venous thrombosis

Payne, Holly (2018). Novel insights into the mechanisms of venous thrombosis. University of Birmingham. Ph.D.

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Abstract

Venous thrombosis is a major health concern, with an annual incidence of ~1 per 1000 adults (Cushman 2007). This includes deep vein thrombosis (DVT) and pulmonary embolism (PE), the fatal consequence of a clot detaching and moving to the lungs, together these diseases are termed venous thromboembolism (VTE). Current treatment options for VTE are often associated with serious side effects and bleeding complications, highlighting the need for more effective prophylaxis. This study therefore aimed to identify new targets to treat DVT, which would not have the associated negative side effects.

This study shows the platelet receptor CLEC-2 (C-type lectin receptor 2) plays an important role in DVT, probably through interaction with podoplanin in the IVC wall, and that lack of CLEC-2 is protective in this disease. We show other immune cells may also play a role in DVT, and demonstrate that mast cell deficiency is protective in vivo. Furthermore, we suggest that the mast cell constituent responsible for the prothrombotic phenotype is likely to be histamine. Preliminary data also suggests that T-cells may have a protective role in DVT, and that thrombin may be important for the release of neutrophil extracellular traps (NETs) from neutrophils inside a growing thrombus.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):