Researchers from RCSI University of Medicine and Health Sciences have uncovered a novel mechanism linking inflammatory bowel disease (IBD) with an increased risk of a serious blood clotting disorder, venous thromboembolism.

The study, published in Nature Communications, identifies a specific subset of immune cells that may contribute to excessive blood clotting in IBD patients, revealing potential therapeutic targets for reducing this risk.

IBD, which includes Crohn’s disease and ulcerative colitis, affects millions worldwide and is associated with systemic inflammation. Patients with IBD face a significantly higher risk of developing blood clotting complications, including deep vein thrombosis and pulmonary embolism, but the underlying causes have remained unclear.

The research team, led by Professor Roger Preston, Associate Professor, RCSI School of Pharmacy and Biomolecular Sciences, discovered that activated immune cells called CD4+ T cells, which are critical in IBD-associated inflammation, express tissue factor, a key initiator of blood clotting. These tissue factor-expressing cells were found in both the intestine and bloodstream of IBD patients, suggesting they may contribute to an increased risk of clot formation.

“Understanding the mechanisms behind the heightened clotting risk in IBD patients is crucial for developing safer, more targeted treatments,” said Prof. Preston. “Our findings show that this subset of T cells not only drive gut inflammation but also have the potential to contribute to blood clotting, which may help us understand why IBD patients face a greater risk of serious clotting disorders.”

The study also pointed to a possible solution. The team found that activated protein C (APC), an anti-inflammatory and anticoagulant protein in the blood, can help counteract the clotting activity of these T cells. When attached to the T cells, APC reduces their ability to trigger clot formation, offering a potential new treatment approach.

“These findings are particularly exciting because they suggest that targeting this pathway in T cells could help manage clotting risk in IBD patients,” added Prof. Preston.

With IBD incidence rising globally, this research has important implications for improving patient outcomes. Current anticoagulant therapies carry bleeding risks, making targeted anti-inflammatory approaches such as an APC-based strategy particularly promising.

The study was supported by funding from Research Ireland, Children’s Health Ireland and the Health Research Board.