IBD: A vascular disorder? The case for heparin therapy

In recent years, heparin has emerged as a possible therapy for inflammatory bowel disease (IBD). Several recent, strongly positive, open-labeled series of heparin in both ulcerative colitis (UC) and Crohn's disease (CD) reinforce the work of Gaffney and co-workers that suggested a benefit of heparin in UC. Although counterintuitive as a therapy for a disorder characterized by bleeding, heparin is intriguing also for implications with regard to the pathophysiology of UC and CD. Although the thromboembolic complications and hypercoagulable state associating flares of both UC and CD suggest that heparin may produce a benefit by treating microthrombi in the intestinal circulation, recent IBD research suggests that a broader endothelial dysfunction in regulation of coagulation, inflammation, and vascular repair may be important events in the pathogenesis of IBD. Heparin, with its diverse effects targeting the endothelium, may be an ideal agent to reverse these defects and produce significant therapeutic benefits in both UC and CD. Randomized, controlled trials currently in progress will help determine whether heparin and the endothelial cell are but another epiphenomenon in IBD or provide important clues to understanding its pathogenesis.