Abstract: Five studies were eligible for inclusion (329 patients). Three studies (270 patients) compared low molecular weight heparin to placebo, one study (34 patients) compared LMWH in addition to standard therapy, and one study (25 patients) compared UFH to corticosteroids. The study comparing UFH to corticosteroids was rated at high risk of bias due to a single-blind design. The study that compared the addition of LMWH to standard therapy to standard therapy alone was rated at high risk of bias due to open-label design. The other three studies were rated as low risk of bias. LMWH administered subcutaneously showed no benefit over placebo for any outcome, including clinical remission (very low quality of evidence), and clinical, endoscopic, or histological improvement. High dose LMWH administered via an extended colon-release tablet demonstrated benefit over placebo for clinical remission (RR 1.39; 95% CI 1.09 to 1.77 ; P = 0.008; very low quality of evidence), clinical improvement (RR 1.28; 95% CI 1.06 to 1.55; P = 0.01; very low quality of evidence), and endoscopic improvement (RR 1.21; 95% CI 1.00 to 1.47 ; P = 0.05) but not endoscopic remission or histologic improvement. LMWH was not beneficial when added to standard therapy for clinical remission, clinical improvement, endoscopic remission or endoscopic improvement. LMWH was well-tolerated but provided no significant benefit for quality of life. One study examining UFH versus corticosteroids for the treatment of severe UC demonstrated the inferiority of UFH for clinical improvement. More patients assigned to UFH had rectal hemorrhage as an adverse event. There is evidence to suggest that LMWH may be effective for the treatment of active UC. When administered by extended colon-release tablets, LMWH was more effective than placebo for treating outpatients with mild to moderate disease. This benefit needs to be confirmed by further randomized controlled studies. The same benefits were not seen when LMWH was administered subcutaneously at lower doses. There is no evidence to support the use of UFH for the treatment of active UC. A further trial of UFH in patients with mild disease may also be justified. Any benefit found would need to be weighed against a possible increased risk of rectal bleeding in patients with active UC.

Plain-language summary: The researchers identified five studies that included a total of 329 patients. Three studies (270 patients) compared low molecular weight heparin to placebo (e.g. a sugar pill), one study (34 patients) compared low molecular weight heparin in addition to standard therapy, and one study (25 patients) compared unfractionated heparin to steroids. The study comparing unfractionated heparin to steroids and the study that compared the addition of low molecular weight heparin to standard therapy to standard therapy alone was judged to be of low quality. The three placebo-controlled studies were judged to be of high quality. In one small study, unfractionated heparin was worse than steroids for inducing clinical improvement (i.e. reduction of symptoms) in people with severe ulcerative colitis. In addition, rectal bleeding was more frequent among people who received unfractionated heparin. In another small study low molecular weight heparin used with standard therapy provided no additional benefit over standard therapy alone in adults with active ulcerative colitis. Low molecular weight heparin administered by injection showed no benefit over placebo for any outcome, including clinical remission (very low quality of evidence), clinical improvement and endoscopic improvement (i.e. healing of inflammation). High dose low molecular weight heparin administered via an extended colon-release tablet demonstrated benefit over placebo for clinical remission, clinical improvement. and endoscopic improvement. This result suggests that high dose low molecular weight heparin administered by extended-release capsules may be effective for the treatment of active ulcerative colitis. However, this result needs to be verified by future clinical trials.