Thrombosis and Inflammatory Bowel Disease Peter M. Irving, K. John Pasi, David S. Rampton  Clinical Gastroenterology and Hepatology  Volume 3, Issue 7, Pages 617-628 (July 2005) DOI: 10.1016/S1542-3565(05)00154-0 Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 1 The coagulation system. Endothelial injury exposes TF, which forms a complex with factor VII. This complex activates factors X and, to a lesser extent, IX. TFPI prevents this activation progressing further; for coagulation to progress, factor Xa must be produced via factors IX and VIII. Thrombin, generated by the initial production of factor Xa, activates factor VIII and, through factor XI, factor IX, resulting in further activation of factor X. This positive feedback loop allows coagulation to proceed. Fibrin polymers are stabilized by factor XIIIa. Activated proteins C+S (APC+S) together inhibit factors VIIIa and Va, whereas antithrombin (AT) inhibits factors VIIa, IXa, Xa, and XIa. Fibrinolysis balances this system through the action of plasmin on fibrin. Plasminogen activator inhibitor controls the plasminogen activator-induced conversion of plasminogen to plasmin. Clinical Gastroenterology and Hepatology 2005 3, 617-628DOI: (10.1016/S1542-3565(05)00154-0) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 2 The roles of activated platelets and PLAs in mucosal inflammation. Activated platelets can interact with other cells involved in the inflammatory response either through direct contact or through the release of soluble mediators. Activated platelets interact directly with activated vascular endothelium, causing the latter to express adhesion molecules and release inflammatory and chemotactic cytokines. Activated platelets can also aggregate with leukocytes, further activating the constituent platelets and leukocytes. The resultant PLAs are more likely to adhere to vascular endothelium than leukocytes that circulate alone. Platelets also release a host of soluble mediators that have a broad range of effects on intravascular and extravascular cells; for example, they attract and activate leukocytes, activate vascular endothelium, and cause fibroblast proliferation. ICAM-1, intercellular adhesion molecule 1; VCAM-1, vascular cell adhesion molecule 1; IL-1, interleukin-1; PAF, platelet-activating factor, TGF-β, tumor growth factor-β; MCP-3, monocyte chemoattractant protein-3; PDGF, platelet-derived growth factor; RANTES, regulated on activation, normal T-cell expressed and secreted. Clinical Gastroenterology and Hepatology 2005 3, 617-628DOI: (10.1016/S1542-3565(05)00154-0) Copyright © 2005 American Gastroenterological Association Terms and Conditions