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DOI: 10.1055/s-0035-1556590
Hypercoagulability and Platelet Abnormalities in Inflammatory Bowel Disease
Publikationsverlauf
Publikationsdatum:
13. August 2015 (online)
Abstract
Patients with inflammatory bowel disease (IBD) exhibit a threefold higher risk for development of systemic thrombosis than the general population. Although the underlying causes of the increased risk for thrombus development remain poorly understood, there is a large body of evidence suggesting that abnormalities in coagulation, fibrinolysis, and platelet function may contribute to this response. Changes in hemostatic biomarkers are consistent with subclinical activation of coagulation system, including tissue factor activation, impaired protein C pathway, enhanced thrombin generation, and diminished fibrinolytic capacity. There is also evidence for an increased production and reactivity of platelets, with an enhanced formation of platelet–platelet and platelet–leukocyte aggregates. The altered coagulation and platelet function, and the predisposition to thrombus formation have also been demonstrated in animal models of IBD. The animal studies have revealed a major role for inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, as mediators of the platelet abnormalities and enhanced thrombus development in experimental IBD. These findings in animal models raise hope for the development of novel therapeutic strategies to reduce thrombosis-related mortality in IBD patients.
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References
- 1 Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med 2009; 361 (21) 2066-2078
- 2 Esmon CT. The impact of the inflammatory response on coagulation. Thromb Res 2004; 114 (5-6) 321-327
- 3 Yoshida H, Granger DN. Inflammatory bowel disease: a paradigm for the link between coagulation and inflammation. Inflamm Bowel Dis 2009; 15 (8) 1245-1255
- 4 Irving PM, Pasi KJ, Rampton DS. Thrombosis and inflammatory bowel disease. Clin Gastroenterol Hepatol 2005; 3 (7) 617-628
- 5 Levi M, van der Poll T. Two-way interactions between inflammation and coagulation. Trends Cardiovasc Med 2005; 15 (7) 254-259
- 6 Twig G, Zandman-Goddard G, Szyper-Kravitz M, Shoenfeld Y. Systemic thromboembolism in inflammatory bowel disease: mechanisms and clinical applications. Ann N Y Acad Sci 2005; 1051: 166-173
- 7 Alkim H, Ayaz S, Alkim C, Ulker A, Sahin B. Continuous active state of coagulation system in patients with nonthrombotic inflammatory bowel disease. Clin Appl Thromb Hemost 2011; 17 (6) 600-604
- 8 Deutschmann A, Schlagenhauf A, Leschnik B, Hoffmann KM, Hauer A, Muntean W. Increased procoagulant function of microparticles in pediatric inflammatory bowel disease: role in increased thrombin generation. J Pediatr Gastroenterol Nutr 2013; 56 (4) 401-407
- 9 Scaldaferri F, Sans M, Vetrano S , et al. Crucial role of the protein C pathway in governing microvascular inflammation in inflammatory bowel disease. J Clin Invest 2007; 117 (7) 1951-1960
- 10 Danese S, Papa A, Saibeni S, Repici A, Malesci A, Vecchi M. Inflammation and coagulation in inflammatory bowel disease: The clot thickens. Am J Gastroenterol 2007; 102 (1) 174-186
- 11 Danese S, Papa A. PAI-1 and TAFI in inflammatory bowel disease: the yin and yang of the fibrinolytic system. Eur J Gastroenterol Hepatol 2008; 20 (9) 826-828
- 12 Juhlin L, Krause U, Shelley WB. Endotoxin-induced microclots in ulcerative colitis and Crohn's disease. Scand J Gastroenterol 1980; 15 (3) 311-314
- 13 Jackson LM, O'Gorman PJ, O'Connell J, Cronin CC, Cotter KP, Shanahan F. Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and Factor V Leiden. Q J Med 1997; 90: 183-188
- 14 Anthoni C, Russell J, Wood KC , et al. Tissue factor: a mediator of inflammatory cell recruitment, tissue injury, and thrombus formation in experimental colitis. J Exp Med 2007; 204 (7) 1595-1601
- 15 Stouthard JM, Levi M, Hack CE , et al. Interleukin-6 stimulates coagulation, not fibrinolysis, in humans. Thromb Haemost 1996; 76 (5) 738-742
- 16 Kvietys PR, Granger DN. Role of reactive oxygen and nitrogen species in the vascular responses to inflammation. Free Radic Biol Med 2012; 52 (3) 556-592
- 17 Görlach A. Redox regulation of the coagulation cascade. Antioxid Redox Signal 2005; 7 (9-10) 1398-1404
- 18 Collins CE, Cahill MR, Newland AC, Rampton DS. Platelets circulate in an activated state in inflammatory bowel disease. Gastroenterology 1994; 106 (4) 840-845
- 19 Collins CE, Rampton DS. Platelet dysfunction: a new dimension in inflammatory bowel disease. Gut 1995; 36 (1) 5-8
- 20 Danese S, de la Motte C, Sturm A , et al. Platelets trigger a CD40-dependent inflammatory response in the microvasculature of inflammatory bowel disease patients. Gastroenterology 2003; 124 (5) 1249-1264
- 21 Öztürk ZA, Dag MS, Kuyumcu ME , et al. Could platelet indices be new biomarkers for inflammatory bowel diseases?. Eur Rev Med Pharmacol Sci 2013; 17 (3) 334-341
- 22 Harries AD, Fitzsimons E, Fifield R, Dew MJ, Rhoades J. Platelet count: a simple measure of activity in Crohn's disease. Br Med J (Clin Res Ed) 1983; 286 (6376) 1476
- 23 Heits F, Stahl M, Ludwig D, Stange EF, Jelkmann W. Elevated serum thrombopoietin and interleukin-6 concentrations in thrombocytosis associated with inflammatory bowel disease. J Interferon Cytokine Res 1999; 19 (7) 757-760
- 24 Yan SL, Russell J, Harris NR, Senchenkova EY, Yildirim A, Granger DN. Platelet abnormalities during colonic inflammation. Inflamm Bowel Dis 2013; 19 (6) 1245-1253
- 25 Yan SL, Russell J, Granger DN. Platelet activation and platelet-leukocyte aggregation elicited in experimental colitis are mediated by interleukin-6. Inflamm Bowel Dis 2014; 20 (2) 353-362
- 26 Senchenkova EY, Komoto S, Russell J , et al. Interleukin-6 mediates the platelet abnormalities and thrombogenesis associated with experimental colitis. Am J Pathol 2013; 183 (1) 173-181
- 27 Collins CE, Rampton DS, Rogers J, Williams NS. Platelet aggregation and neutrophil sequestration in the mesenteric circulation in inflammatory bowel disease. Eur J Gastroenterol Hepatol 1997; 9 (12) 1213-1217
- 28 Danese S, Katz JA, Saibeni S , et al. Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients. Gut 2003; 52 (10) 1435-1441
- 29 André P, Prasad KS, Denis CV , et al. CD40L stabilizes arterial thrombi by a beta3 integrin—dependent mechanism. Nat Med 2002; 8 (3) 247-252
- 30 Stokes KY, Granger DN. Platelets: a critical link between inflammation and microvascular dysfunction. J Physiol 2012; 590 (Pt 5): 1023-1034
- 31 Webberley MJ, Hart MT, Melikian V. Thromboembolism in inflammatory bowel disease: role of platelets. Gut 1993; 34 (2) 247-251
- 32 Andoh A, Yoshida T, Yagi Y , et al. Increased aggregation response of platelets in patients with inflammatory bowel disease. J Gastroenterol 2006; 41 (1) 47-54
- 33 Yoshida H, Russell J, Senchenkova EY, Almeida Paula LD, Granger DN. Interleukin-1beta mediates the extra-intestinal thrombosis associated with experimental colitis. Am J Pathol 2010; 177 (6) 2774-2781
- 34 Irving PM, Macey MG, Shah U, Webb L, Langmead L, Rampton DS. Formation of platelet-leukocyte aggregates in inflammatory bowel disease. Inflamm Bowel Dis 2004; 10 (4) 361-372
- 35 Irving PM, Macey MG, Feakins RM , et al. Platelet-leucocyte aggregates form in the mesenteric vasculature in patients with ulcerative colitis. Eur J Gastroenterol Hepatol 2008; 20 (4) 283-289
- 36 Vowinkel T, Anthoni C, Wood KC , et al. CD40-CD40 ligand mediates the recruitment of leukocytes and platelets in the inflamed murine colon. Gastroenterology 2007; 132 (3) 955-965
- 37 Vowinkel T, Wood KC, Stokes KY , et al. Mechanisms of platelet and leukocyte recruitment in experimental colitis. Am J Physiol Gastrointest Liver Physiol 2007; 293 (5) G1054-G1060
- 38 Cognat E, Crassard I, Denier C, Vahedi K, Bousser MG. Cerebral venous thrombosis in inflammatory bowel diseases: eight cases and literature review. Int J Stroke 2011; 6 (6) 487-492
- 39 Miehsler W, Reinisch W, Valic E , et al. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism?. Gut 2004; 53 (4) 542-548
- 40 Grisham MB. Do different animal models of IBD serve different purposes?. Inflamm Bowel Dis 2008; 14 (Suppl. 02) S132-S133
- 41 Yoshida H, Russell J, Granger DN. Thrombin mediates the extraintestinal thrombosis associated with experimental colitis. Am J Physiol Gastrointest Liver Physiol 2008; 295 (5) G904-G908
- 42 Yoshida H, Russell J, Stokes KY, Yilmaz CE, Esmon CT, Granger DN. Role of the protein C pathway in the extraintestinal thrombosis associated with murine colitis. Gastroenterology 2008; 135 (3) 882-888
- 43 Yoshida H, Yilmaz CE, Granger DN. Role of tumor necrosis factor-α in the extraintestinal thrombosis associated with colonic inflammation. Inflamm Bowel Dis 2011; 17 (11) 2217-2223
- 44 Mudter J, Neurath MF. Il-6 signaling in inflammatory bowel disease: pathophysiological role and clinical relevance. Inflamm Bowel Dis 2007; 13 (8) 1016-1023
- 45 Gavins FN, Li G, Russell J, Perretti M, Granger DN. Microvascular thrombosis and CD40/CD40L signaling. J Thromb Haemost 2011; 9 (3) 574-581