Coagulation factor XIII and markers of thrombin generation and fibrinolysis in patients with inflammatory bowel disease.

Abstract

To relate factor XIII levels and other prothrombotic markers to inflammatory bowel disease and investigate the frequency of valine34leucine and its effect on factor XIII cross-linking activity in patients with inflammatory bowel disease. Fifty patients with active inflammatory bowel disease but no venous thromboembolism (32 with ulcerative colitis, 18 with Crohn's disease), 50 patients with inactive inflammatory bowel disease but no venous thromboembolism (32 with ulcerative colitis, 18 with Crohn's disease), two age- and gender-matched healthy control groups of 100 subjects each were recruited. To further explore the relationship between valine34leucine and inflammatory bowel disease, 21 patients with the disease (13 with ulcerative colitis and eight with Crohn's disease) and venous thromoembolism (male to female ratio = 7 : 14, median age 59.5 years (range, 19-80 years)) were recruited. Two hundred and fifteen control subjects (M : F = 121 : 94, median age 62 years (28-74 years)), with venous thromboembolism (119 with deep venous thrombosis, and 96 with pulmonary embolism) were drawn from the same geographical area as the patients. Factor XIII A, B-subunit antigen and A2B2 tetramer levels were measured using an in-house sandwich enzyme-linked immunoassay method. Factor XIII A2B2 tetramer and the A-subunit were significantly decreased in patients with active inflammatory bowel disease compared with controls (59% vs 95%, P < 0.0001 and 75% vs 102%, P < 0.0001, respectively), but not between the inactive inflammatory bowel disease group and controls. The D-dimer and prothrombin 1+2 fragment levels in patients with active inflammatory bowel disease were raised compared with controls (178 (152) vs 109 (84), P = 0.0007 and 82 (43) vs 55 (28), P = 0.0001, respectively). The factor XIII B-subunit and factor XIII cross-linking activity were not significantly different between patients with active or inactive inflammatory bowel disease and controls. There was no significant difference in genotype distribution in inflammatory bowel disease patients with or without venous thromboembolism and respective control subjects. Levels of tissue plasminogen activator antigen were significantly increased in patients with active inflammatory bowel disease when compared to inactive inflammatory bowel disease and controls (8.9 (3.7) vs 6.7 (3.4) vs 6.9 (3.4), P < 0.001). Active inflammatory bowel disease is associated with activation of coagulation. Factor XIII A and A2B2 tetramer levels were markedly decreased in active inflammatory bowel disease. Variations in the level of factor XIII in patients with inflammatory bowel disease could be multifactorial and in part may result from the increased formation of microthrombi and accelerated turnover of the factor XIII. We found no evidence of association of factor XIII valine34leucine polymorphism and inflammatory bowel disease.