Review article: potential therapeutic applications and mechanisms of action of heparin in inflammatory bowel disease

Unfractioned heparin was recently reported to be beneficial in the treatment of inflammatory bowel disease. The available uncontrolled data show that it may be effective in steroid-resistant ulcerative colitis with a percentage of complete clinical remission of over 70% after an average of 4-6 weeks of therapy. The administration of unfractioned heparin is not currently justified by the very limited available data. The worsening of rectal bleeding is infrequent in treated ulcerative colitis patients and only rarely does it require blood transfusion or a colectomy. Low molecular weight heparin was used in a single trial in patients with steroid-refractory ulcerative colitis, with results similar to those observed with unfractioned heparin. Since a prothrombotic state has been described in inflammatory bowel disease, and microvascular intestinal occlusion seems to play a role in the pathogenesis of inflammatory bowel disease, it is reasonable that part of the beneficial effects of unfractioned heparin in inflammatory bowel disease may result from its anticoagulant properties. However, beyond its well-known anticoagulant activity, unfractioned heparin also exhibits a broad spectrum of immunomodulating and anti-inflammatory properties, by inhibiting the recruitment of neutrophils and reducing pro-inflammatory cytokines. Moreover, it can restore the high-affinity receptor binding of basic fibroblast growth factor and this would aid healing of the ulcerated mucosa. In conclusion, unfractioned heparin may represent a safe therapeutic option for severe, steroid-resistant ulcerative colitis, although randomized, controlled trials are needed to confirm these data.