See “Increased Procoagulant Function of Microparticles in Pediatric Inflammatory Bowel Disease: Role in Increased Thrombin Generation” by Deutschmann et al on page 401.
The activation of coagulation is a significant constituent of the inflammatory response and probably pathogenesis of inflammatory bowel disease (IBD). The etiology of thromboembolism (TE) in IBD seems to be multifactorial but is largely attributable to the coagulation activation during systemic inflammation. Several investigators presented evidence for intravascular thrombin generation in patients with IBD (1). Presently, no single laboratory marker has TE predictive value; however, Saibeni at al (2) demonstrated that recently developed endogenous thrombin potential (ETP) is increased in adult patients with IBD. In contrast to coagulation intermediates or fragments, which are markers of thrombin already generated, the ETP quantifies thrombin activity that can be generated in plasma. Tissue factor, a main initiator of coagulation activation, has been demonstrated to be expressed in monocytes of patients with Crohn disease, and in intestinal mucosal vasculature in both Crohn disease and ulcerative colitis (UC) (1). In addition, the cell components called microparticles have recently been found to be increased in the plasma of patients with IBD (3). There are vesicles of cell membrane mainly from activated platelets with expression of the tissue factor on their surface, suggesting their role in coagulation activation, and in turn prothrombotic potential.
In the present issue of Journal of Pediatric Gastroenterology and Nutrition, Deutschmann et al presents evidence that microparticles’ procoagulant activity was significantly increased in patients with active and quiescent Crohn disease and active UC (4). These authors have also shown that ETP level was significantly higher in pediatric patients with IBD with active and quiescent stages; however, they observed moderate influence of microparticles on thrombin generation only in patients with active UC. The observation by Deutschmann et al that increased procoagulant function of microparticles is not a major cause for higher thrombin generation in patients with IBD is not surprising. The ETP test is extremely sensitive to variations of prothrombin and antithrombin capacity. Nevertheless, the authors demonstrated increased procoagulant function of microparticles in pediatric patients with IBD. It is likely that the tissue factor expressed on the surface of microparticles or delivered to the site of thrombosis via circulating blood cells and microparticles may initiate an event in the extraintestinal thrombosis elicited during IBD. Although many aspects of microparticles function are still unclear, it seems that they in vivo play an important role in inflammation, releasing inflammatory mediators and modulating endothelial cells (5). Because microparticles in IBD circulate in the inflammatory state, it appears logical that they may act as inflammatory components. The TE complications in IBD, including pediatric patients with IBD, do not appear to decline, despite awareness concerning TE events and improved treatment (1,6). Interestingly, it has been shown that treatment with infliximab, an anti-tumor necrosis factor-α antibody, reduced the level of circulating microparticles in patients with active Crohn disease (3). The increased ETP is demonstrated in both active and quiescent stages of pediatric patients with IBD, which indicates that procoagulant potential is a feature of the disease. As postulated by Saibeni et al (2) and Deutschmann et al (4), prospective studies are needed to evaluate ETP clinical value stratifying the TE risk in patients with IBD.
1. Stadnicki A. Involvement of coagulation and hemostasis in inflammatory bowel diseases. Curr Vasc Pharmacol
2. Saibeni S, Saladino V, Cantarangkul V, et al. Increased thrombin generation in inflammatory bowel diseases. Thromb Res
3. Chamouard P, Desprez D, Hugel B, et al. Circulating cell-derived microparticles in Crohn's disease. Dig Dis Sci
4. Deutschmann A, Schlagenhauf A, Leschnik B, et al. Increased procoagulant function of microparticles in pediatric inflammatory bowel disease: role in increased thrombin generation. J Pediatr Gastroenterol Nutr
5. Ratajczak J, Wysoczynski M, Hayek F, et al. Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia
6. Kappelman MD, Horvath-Puho E, Sandler RS, et al. Thromboembolic risk among Danish children and adults with inflammatory bowel diseases: a population-based nationwide study. Gut