Increased Thrombotic Risk in Patients with Myeloproliferative Neoplasms: Linking Inflammation, Metabolism and Hypercoagulability - the CLIMB study

Blood clotting is an important defence mechanism that prevents blood loss after injury, but when this process is not controlled, it can block blood vessels and cause life-threatening thrombosis. Individuals with myeloproliferative neoplasms (MPNs) generate excessive numbers of all blood cells, including white cells, which predisposes them to an increased risk of dangerous blood clots. As a result, 1 in 3 MPN patients will suffer a thrombotic event in their lifetime. The reasons why high white blood cell count increases the risk of thrombosis in individuals with MPNs, however, is poorly understood, limiting our capacity to develop safe and target anti-thrombotic drugs for this at-risk patient population.

Monocytes are white blood cells that become ‘activated’ in healthy individuals in response to stress or infection, and in doing so, speed up their metabolism to fuel inflammation as part of the immune response. Notably, individuals with MPNs have been shown to have activated white blood cells in the absence of infection. In this study, we want to study how monocytes from individuals with MPNs contribute to the increased likelihood of developing a life-threatening clot. Activated monocytes generate energy differently to normal monocytes, and recent exciting work from our lab has shown that these changes in cell energy production are critical for increased blood clotting. This is important, because it suggests that it may be possible to re-purpose currently available drugs that ‘re-wire’ activated monocyte metabolism to reduce dangerous clotting activity in MPN patients. In this study, we will evaluate how monocytes isolated from MPN patients are more procoagulant in plasma and test whether drugs that regulate cell metabolism may have anticoagulant properties. These drugs could represent a new approach to slow down blood clotting in MPN patients, and in doing so, safely reduce their risk of life-threatening thrombosis.

Award Date
01 July 2022
Award Value
Principal Investigator
Dr Roger Preston
Host Institution
Royal College of Surgeons in Ireland
Investigator Led Projects