Heparins in ulcerative colitis: proposed mechanisms of action and potential reasons for inconsistent clinical outcomes

Abstract

Current drug therapies for ulcerative colitis (UC) are not completely effective in managing moderate-to-severe UC and approximately 20% of patients with severe UC require surgical interventions. Heparins, polydisperse mixtures of non-anticoagulant and anticoagulant oligosaccharides, are widely used as anticoagulants. However, heparins are also reported to have anti-inflammatory properties. Unfractionated heparin was initially used in patients with UC for the treatment of rectal microthrombi. Surprisingly, it was found to be effective in reducing UC-associated symptoms. Since then, several pre-clinical and clinical studies have reported promising outcomes of heparins in UC. In contrast, some controlled clinical trials demonstrated no or only limited benefits, thus the potential of heparins for the treatment of UC remains uncertain. This review discusses potential mechanisms of action of heparins, as well as proposed reasons for their contradictory clinical effectiveness in the treatment of UC.

Keywords:

• heparin
• inflammatory bowel disease
• low molecular weight heparin
• mechanism
• ulcerative colitis

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Current treatments for ulcerative colitis (UC) are either not effective or associated with severe side effects.

• Heparins, mixture of anticoagulant and non-anticoagulant oligosaccharides, are shown to be effective when used for the treatment of UC.

• Non-anticoagulant oligosaccharides are reported to be responsible for heparins anti-inflammatory properties.

• Presence of anticoagulant oligosaccharides can increase the risk of bleeding when heparins are used in UC.

• Isolation and identification of non-anticoagulant oligosaccharide(s) could provide a new way for oligosaccharide-based therapies in UC patients.

Notes