Inherited disorders of coagulation appear to protect against inflammatory bowel disease

Thompson, Nick; Wakefield, Andrew J.; Pounder, R. E.

doi:10.1016/0016-5085(95)90197-3

Cited by 132 publications

(79 citation statements)

References 24 publications

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“…25 Moreover inherited disorders of coagulation appear to protect against ulcerative colitis. 26 This study demonstrates a promising response to standard heparin in patients with ulcerative colitis resistant to conventional treatment. There is now a clear need for a controlled trial of heparin in ulcerative colitis and also a need for further work on the role of heparin in the modulation of neutrophil±endothelial interactions.…”

Section: Discussionmentioning

confidence: 72%

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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Section: Discussionmentioning

confidence: 72%

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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“…39,51,52 It is debated whether this evidence of coagulatory cascade activation is secondary to chronic inflammation or represents a primary feature of IBD, independent of disease clinical activity. The potential protective effect of an underlying bleeding predisposition in preventing the development of IBD was investigated by Thompson and colleagues,53 who found a significantly decreased risk of development of either CD or UC among patients with either hemophilia or von Willebrand's disease. The authors concluded that a congenital bleeding predisposition exerted a protective effect against development of IBD, suggesting an important role of inappropriate coagulation and vascular occlusion in the pathogenesis of human IBD.…”

Section: Hypercoagulability and Prothrombotic State In Ibdmentioning

confidence: 99%

“…The authors concluded that a congenital bleeding predisposition exerted a protective effect against development of IBD, suggesting an important role of inappropriate coagulation and vascular occlusion in the pathogenesis of human IBD. 53 In IBD, increased plasmatic levels of several recognized risk factors for thrombosis, such as increased levels of factors V, VII, and VIII 54 , lipoprotein (a) 55 , and fibrinogen, 54 as well as reduced fibrinolytic activity, have been consistently described, indicating a prothrombotic condition.…”

Section: Hypercoagulability and Prothrombotic State In Ibdmentioning

confidence: 99%

“…In fact, one of the earliest abnormalities in CD mucosa is the presence of platelet thrombi crosslinked with fibrin in the mucosal microvasculature. 56 Indeed, crucial changes to the mucosal microvasculature comprising vascular injury, focal arteritis, fibrin deposition, microinfarction, and neoangiogenesis have been observed in CD, 53 as well as intracapillary clots in rectal biopsies of UC patients. 34 Moreover, endothelial injury and disruption could lead to exposure of the subendothelial matrix, to which platelets are strongly attracted, thus further promoting microthrombi formation.…”

Section: Hypercoagulability and Prothrombotic State In Ibdmentioning

confidence: 99%

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Multiple Pathogenic Roles of Microvasculature in Inflammatory Bowel Disease: A Jack of All Trades

Deban

Correale

Vetrano

et al. 2008

The American Journal of Pathology

125

100

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The etiology of Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD), is still largely unknown. However, it is now clear that the abnormalities underlying pathogenesis of intestinal inflammation are not restricted to those mediated by classic immune cells but also involve nonimmune cells. In particular, advances in vascular biology have outlined a central and multifaceted pathogenic role for the microcirculation in the initiation and perpetuation of IBD. The microcirculation and its endothelial lining play a crucial role in mucosal immune homeostasis through tight regulation of the nature and magnitude of leukocyte migration from the intravascular to the interstitial space. Chronically inflamed IBD microvessels display significant alterations in microvascular physiology and function compared with vessels from healthy and uninvolved IBD intestine. The investigation into human IBD has demonstrated how endothelial activation present in chronically inflamed IBD microvessels results in a functional phenotype that also includes leakiness, chemokine and cytokine expression, procoagulant activity, and angiogenesis. This review contemplates the newly uncovered contribution of intestinal microcirculation to pathogenesis and maintenance of chronic intestinal inflammation. In particular, we assess the multiple roles of the microvascular endothelium in innate immunity, leukocyte recruitment, coagulation and perfusion, and immune-driven angiogenesis in IBD.

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“…However, whether exacerbated coagulation participates in the etiology of inflammatory bowel disease remains controversial. It is interesting to note that the risk of inflammatory bowel disease is lower than expected in patients with inherited bleeding disorders (10) and that several observational studies show a beneficial effect of anticoagulant treatment (11)(12)(13)(14). However, a randomized clinical trial did not confirm this beneficial effect of heparin treatment (15).…”

Section: Inflammatory Bowel Disease Patientsmentioning

confidence: 99%

Tissue Factor-Dependent Chemokine Production Aggravates Experimental Colitis

Queiroz

Veer

Berg

et al. 2011

Mol Med

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Inherited disorders of coagulation appear to protect against inflammatory bowel disease

Cited by 132 publications

References 24 publications

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

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

Multiple Pathogenic Roles of Microvasculature in Inflammatory Bowel Disease: A Jack of All Trades

Tissue Factor-Dependent Chemokine Production Aggravates Experimental Colitis

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