Response to heparin in patients with ulcerative colitis

Gaffney, PeterR.; O'Leary, J.P.; Doyle, C. T.; Gaffney, Anne; Hogan, John M.; Smew, Faraj; Annis, P

doi:10.1016/0140-6736(91)92201-c

Cited by 126 publications

(124 citation statements)

References 6 publications

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“…We did however ®nd that more than 90% of our patients experienced symptomatic improvement. In this context, it should be pointed out that we applied a standardized treatment period of 12 weeks, whereas in the UHF study by Gaffney et al, 4 the treatment period varied considerably and 40% of the patients were actually treated for more than 25 weeks. Spontaneous improvement, which can sometimes occur during extended treatment periods, may have attributed to the high remission rate.…”

Section: Discussionmentioning

confidence: 99%

“…15 On the other hand, earlier reports have shown that in¯ammatory bowel disease is associated with a hypercoagulable state and a higher incidence of thromboembolic events and some authors have speculated that the observed effect of UFH was related to its anti-coagulative properties. 4,5 This conclusion was based on the presence of ®brin thrombi in the small vessels of the mucosa and submucosa. However, the appearance of occlusive ®brinoid lesions could be secondary to the in¯ammatory process, rather than being the primary cause of ulcerative colitis.…”

Section: Discussionmentioning

confidence: 99%

“…8,9 In an uncontrolled study, 90% of the patients achieved complete remission. 4 However, this positive effect appeared to be dependent on concomitant SASP treatment, although these patients had not previously responded to SASP per se. In recent SUMMARY Background: Heparin given intravenously has shown bene®cial effects in the treatment of refractory ulcerative colitis in open trials.…”

Section: Introductionmentioning

confidence: 99%

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Low molecular weight heparin as adjuvant therapy in active ulcerative colitis

Törkvist

Thorlacius

Sjöqvist

et al. 1999

Aliment Pharmacol Ther

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Background: Heparin given intravenously has shown beneficial effects in the treatment of refractory ulcerative colitis in open trials. Low molecular weight heparin (LMWH) offers advantages in the method of administration but have not been evaluated in inflammatory bowel disease conditions.Aim: To assess the tolerability and safety of subcutaneous self‐administered LMWH in outpatients with refractory ulcerative colitis and to evaluate any potential adjuvant therapeutic effect.Patients and Methods: Twelve patients with mild to moderately active ulcerative colitis were included in the trial. The patients had either responded poorly to treatment with conventional therapy, including oral and/or rectal glucocorticosteroids, or had experienced a rapid relapse during or shortly after GCS therapy. Dalteparin sodium 5000 units s.c. injection was administered twice daily for 12 weeks. Patients were monitored for possible adverse events and changes in clinical symptoms, and endoscopic and histological scores were analysed. Leucocyte scanning was performed at inclusion and at the end of the study.Results: Tolerability and compliance were excellent and no serious adverse events occurred. Eleven patients improved symptomatically and six (50%) attained complete remission after 12 weeks of treatment. Endoscopic, scintigraphic and histological scores were found to be significantly improved.Conclusion: Self‐administered LMWH given s.c. may be a safe adjuvant therapy for patients with active, glucocorticosteroids‐refractory ulcerative colitis. A controlled trial should be undertaken to confirm the positive effects found in this study.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Low molecular weight heparin as adjuvant therapy in active ulcerative colitis

Törkvist

Thorlacius

Sjöqvist

et al. 1999

Aliment Pharmacol Ther

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“…2±6 Initially heparin was used to treat or prevent thrombo-embolic problems, to which patients with ulcerative colitis are known to have increased susceptibility. Gaffney and colleagues reported 10 patients, nine of whom responded, 4 and a large controlled Russian study reported a reduction in colectomy rate for severe colitis from 19.4% (control) to 6.2% (heparinized). 3 Recently we reported a patient with ulcerative colitis complicated by pyoderma gangrenosum who had a dramatic response to heparin 7 and speculated that the heparin might be exerting its effect via inhibition of neutrophil recruitment.…”

Section: Introductionmentioning

confidence: 99%

Treatment of corticosteroid‐resistant ulcerative colitis with heparin —a report of 16 cases

Evans

Wong

Morris

et al. 1997

Aliment Pharmacol Ther

135

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Background:Heparin, a group of sulphated glycosaminoglycans, in addition to its anticoagulant activity, has a wide range of potentially anti‐inflammatory effects. These include inhibition of neutrophil elastase and inactivation of chemokines. Previous reports of fortuitous improvement in ulcerative colitis patients treated with heparin for prophylaxis of venous thrombosis, prompted us to perform a pilot study in patients with corticosteroid‐resistant ulcerative colitis.Methods:Sixteen hospitalized patients in relapse from ulcerative colitis and unresponsive to high‐dose corticosteroid therapy were treated with intravenous standard heparin (subcutaneous in two patients), the dose was adjusted to provide standard anticoagulant activity. Five patients continued with subcutaneous injections on discharge, with a gradual reduction in the frequency of doses.Results:Within 1 week of starting heparin, 12/16 patients had shown a considerable reduction in stool frequency. After 2 weeks of heparin therapy median stool frequency had improved from 8.0/day (range 6.3–10.0) pre‐treatment to 3.5/day (2.5–5.25) (P=0.008), and by 4 weeks 12/16 achieved clinical remission. Four patients required elective colectomy. Three patients were treated with heparin on a second occasion during a relapse, two failed to respond and required subsequent colectomy. Nine remain well. No serious complications were seen due to the anticoagulant activity, apart from bruising at subcutaneous injection sites.Conclusion:The response to heparin in patients with ulcerative colitis resistant to standard therapy is encouraging and supports the previous uncontrolled evidence for a therapeutic effect. A controlled trial of heparin in ulcerative colitis is clearly indicated.

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“…Experimental and clinical studies in patients with proteinuric glomerulonephritis showed benefit by oral treatment with sulodexide, a mixture of LMW heparin and dermatan sulfate in a Acute respiratory distress syndrome* [5,42] Allergic rhinitis [43] Antimalaric a [44] Antiphospholipid syndrome [45] Asthma and bronchial constriction [5,13] Cardioversion of atrial fibrillation [46] Cardiopathies [47] Chronic obstructive pulmonary diseases [5] Cystic fibrosis [18,48] Glomerulonephritis [26] Hyperlipemias [49] Inflammatory bowel diseases [5,29,50] Mucolytic agent (Inhaled) [51] Nervous system protection by radiation [52] Rheumatoid arthritis [5,53] Severe sepsis [54] Tissue repair and wound healing [5] Vasoprotection [55] a Heparin, inhibiting and reversing cytoadherence and rosetting of Plasmodium falciparium infected erythrocytes "in vitro". Tested from 1967 in severe malaria clinical trials, after some overall promising outcomes, were discontinued due to severe intracranial bleeding [44] 4:1 weight ratio [26].…”

Section: Lmwhs Ultra Lmwhs and Related Oligosaccharides As Nephro-anmentioning

confidence: 99%