Extra‐intestinal thrombosis in experimental colitis

Abstract

Inflammatory bowel disease (IBD) is associated an increased risk for thromboembolism. While thrombosis is known to contribute to morbidity and mortality in IBD, it remains unclear whether this hypercoagulable state can be recapitulated in animal models of colitis. The objectives of this study were to determine whether murine colitis is associated with enhanced thrombus formation in an extra-intestinal vascular bed, and whether genetic overexpression of the endothelial cell protein C receptor (ECPR) offers protection against the thrombus promoting effects of colitis. Intravital microscopy was used to monitor thrombus formation in arterioles and venules of the cremaster muscle in wild type (WT) and ECPR-transgenic mice placed on 3 % dextran sodium sulfate (DSS) in drinking water for 6 days. Thrombus formation was induced using the light/dye endothelial injury model and quantified using the time of onset and completion (blood flow cessation) of the formed thrombus. Our results show that DSS colitis is also associated with an enhanced thrombotic response that is consistent with a pro-coagulant state; this effect was largely manifested in arterioles but not in venules. Overexpression of ECPR significantly delayed thrombus formation. These findings indicate that extra-intestinal thrombus formation is enhanced in experimental IBD and that ECPR affords protection against this response. (P01 DK43785)