Anti‑inflammatory and anticoagulant properties of the protein C system in inflammatory bowel disease

Abstract

In patients with inflammatory bowel disease (IBD), disbalance between procoagulant, anticoagulant, and fibrinolytic factors has been shown. The hemostatic system is an indispensable component of the inflammatory process. Deficiencies in the protein C (PC) pathway components not only promote thrombosis, but also exacerbate inflammation. The aim of the study was to assess the components of the PC system and their correlations with disease activity in patients with IBD. The levels of PC, free protein S (PS), and soluble thrombomodulin (sTM) were measured in 55 consecutive patients with ulcerative colitis (UC), 50 patients with Crohn's disease (CD), and 41 healthy volunteers. Correlations between PC system components and disease activity, hemostatic variables, and inflammatory markers were assessed. sTM levels in patiens with UC were higher compared with controls (24.5 vs. 17.5 ng/ml; P = 0.0042). In patients with IBD, PC activity was higher and PS activity was lower compared with controls (P <0.001). Tumor necrosis factor α (TNF-α) levels were higher in patients with IBD, and interleukin 6 (IL-6) levels were higher only in patients with CD. In patients with UC, a positive correlation was observed between sTM and both PC and PS levels (r = 0.28 and r = 0.34, respectively, P <0.05). Only PC levels correlated with UC activity (r = 0.3, P <0.05). No correlations of TNF-α, IL-6, and C-reactive protein with PC, PS, and sTM levels were observed. The PC pathway is defective in patients with CD and UC. Hypercoagulability in IBD might be associated not only with the inflammatory process but also with disturbances in the anticoagulant system, since defective PC pathway was observed both in active and nonactive disease.