Impaired Fibrinolytic Capacity in Patients with Inflammatory Bowel Disease

Summary

The venous occlusion test was applied to 17 patients with inflammatory bowel disease (IBD; 7 cases of Crohn’s disease, 10 cases of ulcerative colitis). Results were compared to those obtained in 20 healthy matched control subjects. Patients with IBD had significantly decreased t-PA Ag release (p <0.001) and had no significant vWF Ag release. Residual PAI activity was evidenced after venous stasis in the IBD group but not in the control group. Hypofibrinolysis was more important in patients with an evolutive IBD than in patients with IBD in remission. Impaired systemic fibrinolytic capacity might contribute to an increased risk for thromboembolic complications and to the pathogenesis of inflammatory bowel disease.

• References

• 1 Markus G, Camiolo SM, Kohga S, Madeja JM, Mittelman A. Plasminogen activator secretion of human tumors in short-term organ culture, including a comparison of primary and metastatic colon tumors. Cancer Res 1983; 43: 5517-25
• 2 De Bruin PA F, Verspaget HW, Griffin G, Nap M, Verheijen JH, Lamers CB H W. Plasminogen activator activity and composition in human colorectal carcinomas. Fibrinolysis 1987; 1: 57-62
• 3 Tissot JD, Hauert J, Bachmann F. Characterization of plasminogen activators from normal human breast and colon and from breast and colon carcinomas. Int J Cancer 1984; 34: 295-302
• 4 Stephens RW, Fordham CJ, Doe WF. Proenzyme to urokinase-type plasminogen activator in human colon cancer: in vitro inhibition by monocyte minactivin after proteolytic activation. Eur J Cancer Clin Oncol 1987; 23: 213-22
• 5 Kwaan HC, Cocco A, Mendeloff I, Astrup T. Fibrinolytic activity in the normal and inflamed rectal mucosa. Scand J Gastroenterol 1969; 4: 441-5
• 6 De Bruin PA F, Crama-Bohbouth G, Verspaget HW, Verheijen JH, Dooijewaard G, Weterman IT, Lamers CB H W. Plasminogen activators in the intestine of patients with inflammatory bowel disease. Thromb Haemostas 1988; 60: 262-6
• 7 Todd AS. The histological localization of fibrinolysis activator. J Path Bact 1959; 78: 281-3
• 8 Clarke RL, Orandi A, Cliffton EE. Induction of fibrinolysis by venous obstruction. Angiology 1960; 11: 367-70
• 9 Verheijen JH, Chang GT G, Kluft C. Evidence for the occurrence of a fast acting inhibitor for tissue-plasminogen activator in human plasma. Thromb Haemostas 1984; 51: 392-5
• 10 Nguyen G, Horellou MH, Kruithof EK O, Conard J, Samama MM. Residual plasminogen activator inhibitor activity after venous stasis as a criterion for hypofibrinolysis: a study in 83 patients with confirmed deep-vein thrombosis. Blood 1988; 72: 601-5
• 11 Koenigs KP, Mc Phedran P, Spiro HM. Thrombosis in inflammatory bowel disease. J Clin Gastroenterol 1987; 9: 627-31
• 12 Sisbegee B, Rottenberg DA. Sagital sinus thrombosis as a complication of regional enteritis. Ann Neurol 1978; 3: 450-75
• 13 Talbot RW, Heppel J, Dozois RR, Beart RW. Vascular complications of inflammatory bowel disease. Mayo Clin Proc 1986; 61: 140-5
• 14 Staniland JR, Ditchburn J, Dedombal FT. Clinical presentation of diseases of the large bowel. Gastroenterology 1976; 70: 22-8
• 15 Johanson L, Hedner V, Nilsson IM. A family with thromboembolic disease associated with deficient fibrinolytic activity in vessel wall. Acta Med Scand 1978; 203: 477-80
• 16 Nilsson IM, Ljungner H, Tengborn L. Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: low concentrations of plasminogen activator or increased concentrations of plasminogen activator inhibitor. Br Med J 1985; 290: 1453-5
• 17 Juhan-Vague I, Valadier J, Alessi MC, Aillaud MF, Ansaldi J, Philip-Joet C, Holvoet R, Scrradimigni A, Collen D. Deficient t-PA release and elevated PA inhibitor levels in patients with spontaneous or recurrent deep-vein thrombosis. Thromb Haemostas 1987; 57: 67-72
• 18 Lennard-Jones JE, Morson BC, Ritchie JK, Shove DC, Williams CB. Cancer in colitis: assessment of the individual risk by clinical and histological criteria. Gastroenterology 1977; 73: 1280-9
• 19 Gyde SW, Prior P, Macartney JC, Thompson H, Waterhouse J, Allan RW. Malignancy in Crohn’s disease. Gut 1980; 21: 1024-9
• 20 Wakefield AJ, Sawyerr AM, Dhillon AP, Pittilo RM, Rowles PM, Lewis AA M, Pounder RE. Pathogenesis of Crohn’s disease: multifocal gastrointestinal infarction. Lancet 1989; ii: 1057-62
• 21 Stead NW, Bauer KA, Kinney TR. Venous thrombosis in a family with defective release of vascular plasminogen activator and elevated plasma factor VUI/von Willebrand’s factor. Am J Med 1983; 74: 33-9
• 22 Suzuki Y, Tobin A, Quinn D, Whelan D, O’Morian C. Interleukin-1 in inflammatory bowel disease. Gastroenterology 1989; 96: A 498
• 23 Pober JS. Cytokine mediated activation of the vascular endothelium. Am J Pathol 1988; 133: 426-33