Dotan I, Hallak A, Arber N, Santo M, Alexandrowitz A, Knaani Y, Hershkoviz R, Brazowski E, Halpern Z
Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Israel.
Dig Dis Sci. 2001 Oct;46(10):2239-44. doi: 10.1023/a:1011979418914.
Ulcerative colitis is a chronic inflammatory bowel disorder of unknown etiology. Treatment of flare-ups is based on mesalamine and steroids. Treatment of moderate to severe ulcerative colitis with high-dose heparin and low-molecular-weight heparin was reported. The mechanism was assumed to be a combination of anti-coagulant and anti-inflammatory effects. Low-molecular-weight heparin is better and safer than unfractionated heparin. Studies of low-dose low-molecular-weight heparin in experimental models of inflammation and in inflammatory diseases demonstrated a beneficial effect. Our aim in this study was to evaluate the effect of low-dose, low-molecular-weight heparin in active ulcerative colitis. Twelve patients with flare-ups of colitis were prospectively enrolled. Subcutaneous injections of 5-mg enoxaparin were administered at weekly intervals for 12 weeks. Mesalamine doses remained unchanged. Clinical, laboratory, endoscopic, histologic, and quality-of-life scores were evaluated at the beginning and end of the study. Ten patients completed the study. Mean age was 40.1; the female-male ratio was 7:3. Mean Mayo scores were 9.0 +/- 0.94 at baseline and 3.4 +/- 2.0 at the end of the study (P = 0.0001). Endoscopic scores decreased from 2.2 +/- 0.4 to 1.2 +/- 1.0 (P = 0.049) and in 7 of 10 patients extent of disease shortened. A significant increase in IBDQL scores from 135.7 +/- 37.17 to 179.6 +/- 45.15 points was demonstrated (P = 0.0117). Adverse events were one hospitalization due to abdominal pain, arthralgia (1), transient peripheral edema (1), and elevation of alkaline phosphatase (1). During follow-up, one patient required colectomy and another experienced an exacerbation. In conclusion, low-dose low-molecular-weight heparin once a week, combined with mesalamine, may be an effective therapy for active ulcerative colitis. It may delay or preclude the need for steroid treatment. Controlled studies to evaluate efficacy are needed.
溃疡性结肠炎是一种病因不明的慢性炎症性肠病。发作期的治疗以美沙拉嗪和类固醇为基础。有报道称用大剂量肝素和低分子量肝素治疗中度至重度溃疡性结肠炎。其机制被认为是抗凝和抗炎作用的结合。低分子量肝素比普通肝素更好且更安全。在炎症实验模型和炎症性疾病中对低剂量低分子量肝素的研究显示出有益效果。本研究的目的是评估低剂量低分子量肝素对活动性溃疡性结肠炎的影响。前瞻性纳入了12例结肠炎发作患者。每周皮下注射5毫克依诺肝素,共12周。美沙拉嗪剂量保持不变。在研究开始和结束时评估临床、实验室、内镜、组织学和生活质量评分。10例患者完成了研究。平均年龄为40.1岁;男女比例为7:3。平均梅奥评分在基线时为9.0±0.94,在研究结束时为3.4±2.0(P = 0.0001)。内镜评分从2.2±0.4降至1.2±1.0(P = 0.049),10例患者中有7例疾病范围缩短。IBDQL评分从135.7±37.17显著提高至179.6±45.15分(P = 0.0117)。不良事件包括因腹痛住院1次、关节痛1例、短暂性外周水肿1例和碱性磷酸酶升高1例。在随访期间,1例患者需要进行结肠切除术,另1例病情加重。总之,每周一次的低剂量低分子量肝素联合美沙拉嗪可能是活动性溃疡性结肠炎的有效治疗方法。它可能延迟或避免类固醇治疗的需要。需要进行对照研究以评估疗效。