Abstract
Background. Inherited resistance to activated protein C is a common risk factor of venous thrombosis. In a majority of patients the defect is caused by single-point mutation in the gene for factor V. This mutated form of factor Va is more stable against proteolytic attack by activated protein C. The prevalence of this inherited defect in the European population is at least 5%. The risk of thrombosis is increased in the case of heterozygosity 5- to 10-fold, in homozygous subjects 50- to 100-fold, but even homozygous individuals will not necessarily suffer from thrombosis. The aim of our study was to determine whether the presence of Leiden mutation might play a role in the pathophysiology and clinical manifestation of Crohn’s disease. Materials and methods. Thirty-four patients with Crohn’s disease (mean age 34 years, range 21–72 years) were studied. None of them had a history of thrombotic episodes. We examined the case history for risk factors: use of oral contraceptive, steroids, cigarette smoking. Levels of fibrinogen, APTT, lupus anticoagulant and levels of IgG and IgM class anticardiolipin (ACL) antibodies were determined. The Leiden mutation was detected by PCR method (Denninger et al., 1995).
Results. Fibrinogen was elevated in five cases, lupus anticoagulant in one case, but none of the patients had ACL antibodies in the serum. Molecular analyses showed heterozygosity for the Leiden factor V gene mutation in the case of 30 patients (25%).
Conclusion. Thromboembolic events frequently complicate the clinical course of patients with Crohn’s disease; however, we do not have enough knowledge about its role in manifestation of the disease. These results suggested the high frequency of Leiden mutation among our patients and suggest a new genetic background of Crohn’s disease.
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References
Bargen, J. A. and Barker, N. W. (1936). Extensive arterial and venous thrombosis complicating chronic ulcerative colitis, Arch. Intern. Med. 58, 17–31.
Bertina, R. M., Koeleman, B. P., Koster, T., Rosendaal, F. R., Dirven, R. J., de Ronde, H., van der Velden, P. A. and Reitsma, H. P. (1994). Mutation in blood coagulation factor V associated with resistance to activated protein C, Nature 369, 64–67.
Dahlbäck, B., Carlsson, M. and Svensson, P. J. (1993). Familial thrombophilia due to a previously unrecognised mechanism characterised by poor anticoagulant response to activated protein C: Prediction of a cofactor to activated protein C, Proc. Natl. Acad. Sci. USA 90, 1004–1008.
Dahlbäck, B. (1995). New molecular insights into genetics of thrombophilia: resistance to activated protein C caused by Arg506 to Glu mutation of factor V as a pathogenic risk factor for venous thrombosis, Thromb. Haemost. 74, 139–148.
Denninger, M. H., Beldjord, K., Durand, F., Denie, C., Valla, D. and Guillin, M. C. (1995). Budd-Chiari syndrome and factor V Leiden mutation, Lancet 345, 525–526.
Dennis, C. and Karlson, K. E. (1952). Surgical measures as supplements to the management of idiopathic ulcerative colitis: cancer, cirrhosis and arthritis as frequent complications, Surgery 32, 892–912.
Edwards, F. C. and Truelove, S. C. (1964). The course and prognosis of ulcerative colitis, Part III. Complications, Gut 5, 1–15.
Edwards, R. L., Levine, J. B., Green, R. L., Duffy, M, Mathews, E., Brande, W. and Rickles, F. R. (1987). Activation of blood coagulation in Crohn’s disease. Increased plasma fibrinopeptide A levels an enhanced generation of monocyte tissue factor activity, Gastroentemlogy 92, 329–337.
Graef, V., Baggenstoss, A. H., Sauer, W. G. and Spittell, J. A., Jr. (1966). Venous thrombosis occurring in non-specific ulcerative colitis, Arch. Intern. Med. 117, 377–382.
Heneghan, M. A., Cleary, B., Murray, M., O’Gorman, P. J. and McCarthy, C. F. (1998). Activated protein C resistance, thrombophilia, and inflammatory bowel disease, Dig. Dis. Sci. 43, 1356–1361.
Hudson, M., Hutton, R. A., Wakefield, A. J., Sawyer, A. M. and Pounder, R. E. (1992). Evidence for activation of coagulation in Crohn’s disease, Blood Coag Fibrinol. 3, 773–778.
Jackson, L. M., O’Gorman, P. J., O’Conell, J., Cronin, C. C., Cotter, K. P. and Shanahan, F. (1997). Thrombosis in inflammatory bowel disease: Clinical setting, procoagulant profile and factor V Leiden, Q. J. Med. 90, 183–188.
Liebman, H. A., Kashani, N., Sutherland, D., McGehee, W. and Kam, L. (1998). The factor V Leiden mutation increases the risk factor of venous thrombosis in patients with inflammatory bowel disease, Gastroentemlogy 115, 830–834.
Ricketts, W. E. F. and Palmer, W. L. (1946). Complications of chronic non-specific ulcerative colitis, Gastroentemlogy 7, 5–6.
Rosendaal, F. R., Siscovick, D. S., Schwartz, S. M. and Reitsma, H. P. (1996). Increased risk of myocardial infarction associated with factor V Leiden (APC-Resistance) among young women, Blood 86, 2447a.
Sloan, W. P., Jr., Bargen, J. A. and Gage, R. P. (1950). Life histories of patients with ulcerative colitis: a review of 2000 cases, Gastroentemlogy 16, 255–38.
Souto, J. C, Martinez, E., Roca, M., Mateo, J., Pujol, J., Gonzalez, D. and Fontcuberta, J. (1995). Prothrombic state and signs of endothelial lesions in plasma of patients with inflammatory bowel disease, Dig. Dis. Sci. 40, 1883–1889.
Stevens, T. R. J., James, J. P., Simmonds, N. J., McCarthy, D. A., Laurenson, I. F, Maddison, P. J. and Rampton, D. S. (1992). Circulating von Willebrand factor in inflammatory bowel disease, Gut 33, 502–506.
Talbot, R. W., Heppell, J., Dozois, R. and Beart, R. W. (1986). Vascular complications of inflammatory bowel disease, Mayo Clin. Proc. 61, 140–145.
Warren, S. and Sommers, S. C. (1949). Pathogenesis of ulcerative colitis, Am. J. Pathol. 25, 654–677.
Zöller, B. and Dahlbäck, B. (1994). Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis, Lancet 343, 1536–1538.
Zöller, B., Svennson, P. J., He, X. and Dahlbäck, B. (1994). Identification of the same factor V gene mutation in 47 out of 50 thrombosis prone families with inherited resistance to activated protein C, J. Clin. Invest. 94, 2521–2524.
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Nagy, Z., Nagy, Á., Karádi, O. et al. Leiden mutation in patients with Crohn’s disease. Inflammopharmacol 7, 297–301 (1999). https://doi.org/10.1007/s10787-999-0013-0
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DOI: https://doi.org/10.1007/s10787-999-0013-0