Iron deficiency, Intestinal Inflammation, and Thrombosis

Inflammatory bowel disease (IBD) is a condition involving chronic or recurring inflammation of the gut. Patients with IBD have a threefold increased risk for venous thrombosis, with some studies suggesting that arterial thrombotic risk is also increased. Inflammation is known to contribute to thrombotic risk, and indeed more severe disease is leads to more thrombotic events. However, thrombotic events still occur even in patients with no evidence of clinical disease activity. Understanding further contributors to thrombotic disease in IBD would help in increasing the efficacy of preventive strategies. One potential contributor could be iron deficiency (ID) and the associated thrombocytosis. We have previously shown that ID increases thrombotic tendency in animal models of arterial and venous thrombosis. This occurs with increases in platelet number and platelet activity, and is reversed by iron therapy. About a third of all IBD patients suffer from anemia, majority of which is due to ID. They are particularly susceptible due to intestinal blood loss, and inflammation-induced reduction of available iron. Our group has also previously shown that iron therapy in patients with IBD and ID reduces platelet number and platelet activity. Studies in patients with ID also support the link with thrombosis, however it is not clear if it is also a factor in the background of IBD. The aim of this project is to investigate the role of ID in IBD, and to what extent ID- associated changes in platelets contribute to thrombosis in IBD. We will be combining mouse models of IBD (DSS colitis) and thrombosis, to determine if ID resulting from colitis increases thrombotic tendency. We will also examine if iron therapy can reverse these changes, and investigate if this occurs by modulating platelet number and function. We also intend to investigate if ID and iron therapy can modulate colitis, as platelets can contribute to inflammation and ID itself can affect intestinal epithelial health. The results of this project would provide more insight into the factors increasing thrombotic tendency in IBD, and the underscore the importance of iron management.

Inflammatory bowel diseases (IBD) are characterized by long-lasting or recurring inflammation of the intestine. Patients with IBD have a significantly increased risk of developing venous and arterial thrombosis (blood clots). The intestinal inflammation increases the tendency to thrombosis and severe acute illnesses lead to thrombosis more often. However, thrombotic events can often also be seen in IBD patients without clinical disease activity. Therefore, it is important to investigate other risk factors of thrombosis in IBD in order to sharpen the effectiveness of possible preventive strategies. Iron deficiency could be one such risk factor, causing increased platelet count and activity. In previous studies we have shown that iron deficiency increases the risk of thrombosis. Iron therapy reduces this tendency to thrombosis again by normalizing the number and activity of platelets. Two thirds of active IBD patients suffer from iron deficiency. In this project, we wanted to investigate the effect of iron deficiency on the development of thrombosis in patients with inflammatory bowel disease (IBD). We planned to combine mouse models of IBD and thrombosis to see if iron deficiency caused by IBD can increase susceptibility to thrombosis. To do this, we generated mice whose blood platelets fluoresced red through genetic manipulation. During the breeding of these mice, the employment contract of a central researcher was not extended by the Medical University of Vienna (due to the infamous "chain contract regulation"), although her funding was covered by the FWF until the end of the project. As a result, the project had to be terminated prematurely. No data were generated.