Prothrombotic state and signs of endothelial lesion in plasma of patients with inflammatory bowel disease

Abstract

Recent investigations suggest that microthrombi formation in bowel capillaries could be a determinant factor in inflammatory bowel disease (IBD) pathogenesis. To evaluate the implication of the hemostatic system during these thrombotic events, we analyzed plasmatic values of prothrombotic state markers, physiologic inhibitors of coagulation, and endothelial lesion markers in 112 IBD patients. We found an increase in thrombin-antithrombin complexes and a decrease in antithrombin III, probably due to consumption, demonstrating an increase in thrombin generation. High levels of D-dimer reflect increased fibrin formation, but there is no correlation between thrombin generation markers and D-dimer, possibly suggesting the presence of inadequate fibrinolysis. Levels of tissue factor pathway inhibitor were higher in patients than in controls. Nine patients with Crohn's disease (35% of our sample) had levels of this marker under 70% (range 37-69%). Von Willebrand factor values were increased and those of thrombomodulin only in active patients. Most of the changes were detected in patients with inflammatory activity, and there were no differences between ulcerative colitis and Crohn's disease. In conclusion, these results support the hypothesis that there is an endothelial lesion with sustained coagulation activation in IBD patients.

Hyperhomocysteinemia in ulcerative colitis is related to folate levels

“…The incidence of arterial and venous thromboembolic disease in patients with ulcerative colitis (UC) and Crohn's disease (CD) has been reported between 1% and 8% [1,2] , rising to an incidence of 39% in some autopsy studies [3] . Several studies have shown that a hypercoagulable state involving all components of clotting system exists in IBD [4][5][6] . This hypercoagulable state may be related to an increased tendency for thromboembolic events and may be linked to the disease pathogenesis through promoting microthrombi formation in intestinal microcirculation [7,8] .…”

Venous thromboembolism with infl ammatory bowel disease

“…To date, however, no consistent relationship with homocysteinemia and development of thromboembolism has been defined in patients with inflammatory bowel disease [12,13] . Finally, changes associated with subclinical activation of the coagulation cascade [14][15][16] along with diminished factor ⅩⅢ have been reported [16,17] .…”

Kallikrein – Kinin System and Coagulation System in Inflammatory Bowel Diseases

“…Later reports have shown an acquired plasma antithrombin deficiency in active IBD patients, a feature which implies a real risk of thrombosis (Knot et al, 1985). Subsequent studies have shown the presence of increased markers of activate coagulation in both active and quiescent IBD (van Bodegraven et al, 2002;Hudson et al, 1992;Souto et al, 1995). In contrast other investigators did not found a significant increase of coagulation intermediates in IBD patients with an inactive stage (Edwards et al, 1987;Novacek et al, 1997;Stadnicki et al, 1997).…”

“…Natural coagulation inhibitor, protein C plasma level has been shown to be unchanged or decreased in IBD (Larsen et al, 2002)), while decreased its cofactor, protein S plasma level was demonstrated in most studies (Aadland et al, 1994;Saibeni et al, 2001). In addition, an inhibitor of tissue factor, tissue factor protease -inhibitor (TFPI) plasma levels have been reported to be lower in IBD (Souto et al, 1995). Differences between ulcerative colitis and Crohn's diseases including disease location, histology, clinical course and complications although it is likely that both entities share similar immunoregulatory abnormalities and common pathways.…”