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

  • Intestinal Disorders, Inflammatory Bowel Disease, Immunology, and Microbiology
  • Published:
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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 ofd-dimer reflect increased fibrin formation, but there is no correlation between thrombin generation markers andd-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.

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References

  1. Jhons DR: Cerebrovascular complications of inflammatory bowel disease. Am J Gastroenterol 86:367–370, 1991

    PubMed  Google Scholar 

  2. Lam A, Borda IT, Inwood MJ, Thomson S: Coagulation studies in ulcerative colitis and Crohn's disease. Gastroenterology 68:245–251, 1975

    PubMed  Google Scholar 

  3. Talbot RW, Heppell J, Dozois RR, Beart RW: Vascular complications of inflammatory bowel disease. Mayo Clin Proc 61:140–145, 1986

    PubMed  Google Scholar 

  4. Lake AM, Stauffer JQ, Stuart MJ: Hemostatic alterations in inflammatory bowel disease. Response to therapy. Dig Dis 23:897–902, 1978

    Google Scholar 

  5. Knot EAR, ten Cate JW, Leeksma OCh, Tytgat GN, Vreeken J: No evidence for a prethrombotic state in stable chronic inflammatory bowel disease. J Clin Pathol 36:1387–1390, 1983

    PubMed  Google Scholar 

  6. Lambrecht L, Baele G, Barbier F: Hemostatic alterations in Crohn's disease. Acta Clin Belg 42:1:5–11, 1987

    PubMed  Google Scholar 

  7. Jorens PG, Hermans CR, Haber I, Kockx MM, Vermylen J, Parizel GA: Acquired protein C and S deficiency, inflammatory bowel disease and cerebral arterial thrombosis. Blut 61:307–310, 1990

    PubMed  Google Scholar 

  8. Edwards RL, Levine JB, Green R, Duffy M, Mathews E, Brande W, Rickles FR: Activation of blood coagulation in Crohn's disease. Increased plasma fibrinopeptide A levels and enhanced generation of monocyte tissue factor activity. Gastroenterology 92:329–337, 1987

    PubMed  Google Scholar 

  9. van Wersch JWJ, Houben P, Rijken J: Platelet count, platelet function, coagulation activity and fibrinolysis in the acute phase of inflammatory bowel disease. J Clin Chem Clin Biochem 28:513–517, 1990

    PubMed  Google Scholar 

  10. Hudson M, Hutton RA, Wakefield AJ, Sawyer AM, Pounder RE: Evidence for activation of coagulation in Crohn's disease. Blood Coag Fibrinol 3:773–778, 1992

    Google Scholar 

  11. Stevens TRJ, James JP, Simmonds NJ, McCarthy DA, Laurenson IF, Maddison PJ, et al: Circulating von Willebrand factor in inflammatory bowel disease. Gut 33:502–506, 1992

    PubMed  Google Scholar 

  12. Ryu T, Takazoe M, Inoue N, Ukai T, Seta K, Miyajima Y, Kazama M, Kinoshita T: Abnormalities of coagulation and fibrinolysis in patients with Crohn's disease. Thromb Haemostas 69:1060, 1993 (abstract)

    Google Scholar 

  13. Chitolie A, Hudson M, Wakefield AJ, Riddell A, Lee CA, Pounder RE: Tissue factor pathway inhibitor (TFPI) and factor VII in inflammatory bowel disease (IBD). Thromb Hacmostas 69:1081, 1993 (abstract)

    Google Scholar 

  14. Webberly MJ, Hart MT, Melikian V: Thromboembolism in inflammatory bowel disease: Role of platelets. Gut 34:247–251, 1993

    PubMed  Google Scholar 

  15. Wakefield AJ, Dhillon AP, Rowles PM, Sawyerr AM, Pittilo RM, Lewis AAM, et al: Pathogenesis of Crohn's disease: Multifocal gastrointestinal infarction. Lancet 2:1057–1062, 1989

    PubMed  Google Scholar 

  16. Leung FW, Koo A: Mucosal vascular stasis precedes loss of viability of endothelial cells in rat acetic acid colitis. Dig Dis Sci 36:727–732, 1991

    PubMed  Google Scholar 

  17. Fairburn RA: On the actiology of ulcerative colitis. A vascular hypothesis. Lancet 2:697–699, 1973

    Google Scholar 

  18. Harvey RF, Bradshaw JM: A simple index of Crohn's disease activity. Lancet 1:514, 1980

    PubMed  Google Scholar 

  19. Lichtiger S, Present DH: Preliminary report: Cyclosporin in treatment of severe active ulceration colitis. Lancet 336:16–19, 1990

    PubMed  Google Scholar 

  20. Bauer KA, Rosenberg RD: The pathophysiology of the prethrombotic state in humans: Insights gained from studies using markers of hemostatic system activation. Blood 70:343–350, 1987

    PubMed  Google Scholar 

  21. Declerck PJ, Mombaerts P, Holvoet P, de Mol M, Collen D: Fibrinolytic response and fibrin fragment D-dimer level in patients with deep vein thrombosis. Thromb Haemostas 58:1024–1029, 1987

    Google Scholar 

  22. de Jong E, Porte RJ, Knot EAR, Verheijen JH, Dees J: Disturbed fibrinolysis in patients with inflammatory bowel disease. A study in blood plasma, colon mucosa, and faeces. Gut 30:188–194, 1989

    PubMed  Google Scholar 

  23. Conlan MG, Haire WD, Burnett DA: Prothrombotic abnormalities in inflammatory bowel disease. Dig Dis Sci 34:1089–1093, 1989

    PubMed  Google Scholar 

  24. Gris JC, Schved JF, Raffanel C, Dubois A, Ribard D, Balmes JL: Réponse anormale au test d'occlusion veineuse chez les patients atteints de colite cryptogénique. Gastroenterol Clin Biol 15:933–938, 1991

    PubMed  Google Scholar 

  25. Rosenberg RD, Bauer KA: Thrombosis in inherited deficiencies of antithrombin, protein C and protein S. Hum Pathol 18:253–262, 1987

    PubMed  Google Scholar 

  26. Aadland E, Odegaard OR, Roseth A, Try K: Free protein S deficiency in patients with Crohn's disease. Scand J Gastroenterol 29:333–335, 1994

    PubMed  Google Scholar 

  27. Tripodi A, Bertina RM, Connard J, Pabinger I, Sala N, Mannucci PM: Multicenter evaluation of three commerical methods for measuring protein S antigen. Thromb Haemostas 68:149–154, 1992

    Google Scholar 

  28. Broze GJ: Tissue factor pathway inhibitor and the revised hypothesis of blood coagulation. Trends Cardiovasc Med 2:72–77, 1992

    Google Scholar 

  29. Rappaport SI: The extrinsic pathway inhibitor: A regulator of tissue factor-dependent blood coagulation. Thromb Haemostas 66:6–15, 1991

    Google Scholar 

  30. Blann AD, Hopkins J, Winkles J, Wainwright AC: Plasma and serum von Willebrand factor antigen concentration in connective tissue disorders. Ann Clin Biochem 29:67–71, 1992

    PubMed  Google Scholar 

  31. Takano S, Kimura S, Ohdama S, Aoki N: Plasma thrombomodulin in health and diseases. Blood 76:2024–2029, 1990

    PubMed  Google Scholar 

  32. Dittman WA, Majerus PW: Structure and function of thrombomodulin: a natural anticoagulant. Blood 75:329–336, 1990

    PubMed  Google Scholar 

  33. Ruggeri ZM, Ware J: The structure and function of von Willebrand factor. Thromb Haemostas 67:594–599, 1992

    Google Scholar 

  34. Wakefield AJ, Sankey EA, Dhillon AP, Sawyerr AFM, More L, Sim R, et al: Granulomatous vasculitis in Crohn's disease. Gastroenterology 100:1279–1287, 1991

    PubMed  Google Scholar 

  35. Gaffney PR, O'Learny JJ, Doyle CT, Gaffney A, Hogan J, Smew F, et al: Response to heparin in patients with ulcerative colitis. Lancet 337:238–239, 1991 (letter)

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Unit of Hemostasis and Thrombosis, and Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Avda Pare Claret, 167, 08025, Barcelona, Spain

    Joan Carles Souto MD, Elisabet Martínez BSc, Martí Roca PhD, José Mateo MD, Joan Pujol MD, Dolors González MD & Jordi Fontcuberta PhD

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  1. Joan Carles Souto MD
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  2. Elisabet Martínez BSc
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  3. Martí Roca PhD
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  4. José Mateo MD
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  5. Joan Pujol MD
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  6. Dolors González MD
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  7. Jordi Fontcuberta PhD
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Souto, J.C., Martínez, E., Roca, M. et al. Prothrombotic state and signs of endothelial lesion in plasma of patients with inflammatory bowel disease. Digest Dis Sci 40, 1883–1889 (1995). https://doi.org/10.1007/BF02208650

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  • DOI: https://doi.org/10.1007/BF02208650

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