Paradoxical response to heparin in 10 patients with ulcerative colitis

A patient with ulcerative colitis refractory to standard therapy was treated with heparin for a deep vein thrombosis. Paradoxically, rectal bleeding did not increase; instead, his colitis rapidly went into remission. The same effect occurred when this patient was later treated for a pulmonary embolism. On the basis of these observations and reports of a hypercoagulable state in ulcerative colitis, heparin was tested as a therapeutic agent in nine additional patients.

Nine of the 10 patients had ulcerative colitis poorly controlled on sulfasalazine and prednisolone. Two had associated thromboembolic disease, and one was on no medication. Patients were started on heparin in hospital, taught to self-inject subcutaneously, and discharged to continue on 10,000 U of unfractionated heparin twice daily. Current doses of sulfasalazine were maintained; prednisolone was tapered and stopped. Patients were carefully monitored for adverse side-effects. Sections of colonic mucosa from nine patients were examined for intravascular thrombosis of the mucosal blood vessels.

Nine patients became asymptomatic (normal stool frequency, no rectal bleeding) on combined heparin and sulfasalazine therapy; one patient had a partial improvement in symptoms. Highly significant statistical differences between pre- and posttreatment mean scores were found for all disease parameters. Intravascular fibrin thrombi were identified in sections from six of nine patients. No serious complications were associated with this use of heparin.

The heparin-linked remission of ulcerative colitis, observed by chance in our first patient, was followed by similar responses in eight of nine further patients. This suggests that, used as described, heparin may have a role in treating refractory ulcerative colitis.