Skip to main content
Log in

Risk Factors for Thromboembolic Complications in Inflammatory Bowel Disease: The Role of Hyperhomocysteinaemia

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Inflammatory bowel disease (IBD) is associated with an increased risk for thromboembolic events. Aim of this study was to examine the relationship of hyperhomocysteinemia and thrombosis in IBD patients and to assess the role of this factor in addition to other known prothrombotic abnormalities. IBD patients with a history of thrombosis (n = 22) and sex-, age-, and diagnosis-matched IBD controls (n = 23) were studied. Homocysteine (tHcy) was assessed before and after methionine loading. Plasma levels of protein C, protein S, antithrombin III, and fibrinogen and the presence of anticardiolipin and antiphospholipid antibodies were determined and genetic testing for factor V Leiden and the prothrombin gene mutation was performed. Results showed that fasting homocysteine levels in IBD patients with a history of arterial or venous thrombosis tended to be higher than in IBD controls, although not significantly. The increase in homocysteine levels after methionine loading was significantly higher in IBD patients in the arterial thrombosis group than in IBD controls (40.9 ± 17.7 vs. 27.2 ± 9.9 μ M; P < 0.05). Among the other prothrombotic factors, only factor V Leiden was significantly associated with a history of venous thrombosis (20 vs. 0%). At least one risk factor was found in 64% of the IBD patients with previous thromboembolic complications. We conclude that there is an association between hyperhomocysteinemia and a history of arterial thrombosis in IBD patients. We confirm the high prevalence of factor V Leiden in IBD patients with a history of venous thrombosis. In the majority of IBD patients with previous thromboembolic complications, at least one prothrombotic risk factor is detected.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bargen JA, Barker NW: Extensive arterial and venous thrombosis complicating chronic ulcerative colitis. Arch Intern Med 58:17–31, 1936

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Koenigs KP, McPhedran P, Spiro HM: Thrombosis in inflammatory bowel disease. J Clin Gastroenterol 9:617–621, 1987

    Google Scholar 

  • Liebman HA, Kashani N, Sutherland D, et al.: The factor V Leiden mutation increases the risk of venous thrombosis in patients with inflammatory bowel disease. Gastroenterology 115:830–834, 1998

    PubMed  CAS  Google Scholar 

  • Över HH, Ülgen S, Tuglular T, et al.: Thrombophilia and inflammatory bowel disease: Does factor V mutation have a role? Eur J Gastroenterol Hepatol 10:827–829, 1998

    Article  PubMed  Google Scholar 

  • Koutroubakis IE, Sfiridaki A, Mouzas IA, Maladaki A, Kapsoritakis A, Roussomoustakaki M, Kouroumalis EA, Manousos ON: Resistence to activated protein C and low levels of free protein S in Greek patients with inflammatory bowel disease. Am J Gastroenterol 95:190–194, 2000

    PubMed  CAS  Google Scholar 

  • Zauber NP, Sabbath-Solitare M, Rajoria G, et al.: Factor V Leiden mutation is not increased in patients with inflammatory bowel disease. J Clin Gastroenterol 27:215–216, 1998

    PubMed  CAS  Google Scholar 

  • Perry IJ, Refsum H, Morris RW, et al.: Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men Lancet 346:1395–1398, 1995

    Article  PubMed  CAS  Google Scholar 

  • Arnesen E, Refsum H, Bønaa KH, et al.: Serum total homocysteine and coronary heart disease. Int J Epid 24:704–709, 1995

    CAS  Google Scholar 

  • Selhub J, Jacques PF, Bostom AG, et al.: Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N Engl J Med 332:286–291, 1995

    PubMed  CAS  Google Scholar 

  • den Heijer M, Rosendaal FR, Blom HJ, et al.: Hyperhomocysteinemia and venous thrombosis: a meta-analysis. Thromb Haemost 80:874–877, 1998

    PubMed  CAS  Google Scholar 

  • Graham IM, Daly LE, Refsum HM, et al.: Plasma homocysteine as a risk factor for vascular disease. JAMA 277:1775–1781, 1997

    Article  CAS  PubMed  Google Scholar 

  • Frosst P, Blom HJ, Milos R, et al.: A candidate genetic risk factor for vascular isease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111–113, 1995

    CAS  PubMed  Google Scholar 

  • Cattaneo M, Vecchi M, Zighetti ML, et al.: High prevalence of hyperhomocysteinemia in patients with inflammatory bowel disease: a pathogenic link with thromboembolic complications? Thromb Haemost 80:542–545, 1998

    PubMed  CAS  Google Scholar 

  • Mahmud N, Molloy A, McPartlin J, et al.: Increased prevalence of methylenetetrahydrofolate reductase C677T variant in patients with inflammatory bowel disease, and its clinical implications. Gut 45:389–394, 1999

    Article  PubMed  CAS  Google Scholar 

  • Oldenburg B, Fijnheer R, van der Griend R, et al.: Homocysteine in inflammatory bowel disease: a risk factor for thromboembolic complications? Am J Gastroenterol 95:2825–2830, 2000

    PubMed  CAS  Google Scholar 

  • van der Griend R, Haas FJLM, Duran M, et al.: Methionine loading test is necessary for detection of hyperhomocysteinemia. J Lab Clin Med 132:67–72, 1998

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Araki A, Sako Y: Determination of free and total homocysteine in human plasma by high performance liquid chromatography with fluorescence detection. J Chromatogr 422:43–52, 1987

    PubMed  CAS  Google Scholar 

  • Clauss A: Gerinnungs physiologische Schnell method zur bestimmung des fibrinogens. Acta Haematol 17:237–246, 1957

    Article  PubMed  CAS  Google Scholar 

  • Bertina RM, Koeleman BP, Koster T, et al.: Mutation in blood coagulation factor V associated with resistence to activated protein C. Nature 369:64–67, 1994

    Article  CAS  PubMed  Google Scholar 

  • Fijnheer R, Horbach DA, Donders RC, et al.: Factor V Leiden, antiphospholipid antibodies and thrombosis in systemic lupus erythematosus. Thromb Haemost 76:514–517, 1996

    PubMed  CAS  Google Scholar 

  • Poort SR, Rosendaal FR, Reitsma PH, et al.: A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 88:3698–3703, 1996

    CAS  PubMed  Google Scholar 

  • den Heijer M, Blom HJ, Gerrits WBJ, et al.: Is hyperhomocysteinemia a risk factor for recurrent venous thrombosis? Lancet 345:882–885, 1995

    PubMed  CAS  Google Scholar 

  • Graham IM, Daly LE, Refsum HM, et al.: Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA 227:1775–1781, 1997

    Google Scholar 

  • Verhoef P, Kok FJ, Kruyssen DACM, et al.: Plasma total homocysteine, B-vitamins and risk of coronary atherosclerosis. Arterioscler Thromb Vasc Biol 17:989–995, 1997

    PubMed  CAS  Google Scholar 

  • Welch GN, Loscalzo J: Homocysteine and atherothrombosis. N Engl J Med 338:1042–1050, 1998

    PubMed  CAS  Google Scholar 

  • Papa A, De Stefano V, Gasbarrini A, et al.: Prevalence of factor V Leiden and the G20210A prothrombin-gene mutation in inflammatory bowel disease. Blood Coagul Fibrinolysis 11:499–503, 2000

    PubMed  CAS  Google Scholar 

  • Haslam N, Standen GR, Probert CS: An investigation of the association ofthe factor V Leiden mutation and inflammatory bowel disease. Eur J Gastroenterol Hepatol 11:1289–1291, 1999

    PubMed  CAS  Google Scholar 

  • Simioni P, Pranoni P, Lensing AWA, et al.: The risk of recurrent venous thromboembolism in patients with an Arg506 → Gln mutation in the gene for factor V. N Engl J Med 336:399–403, 1997

    CAS  Google Scholar 

  • Vecchi M, Sacchi E, Saibeni S, et al.: Inflammatory bowel diseases are not associated with major hereditary conditions predisposing to thrombosis. Dig Dis Sci 45:1465–1469, 2000

    PubMed  CAS  Google Scholar 

  • Novacek G, Kapiotis S, Moser G, et al.: No evidence of activated blood coagulation in Crohn’s disease. Eur J Gastroenterol Hepatol 9:963–967, 1997

    PubMed  CAS  Google Scholar 

  • De Jong E, Porte RJ, Knot EAR, et al.: Disturbed fibrinolysis in patients with inflammatory bowel disease. A study in blood plasma, colon mucosa, and faeces. Gut 30:188–194, 1989

    PubMed  CAS  Google Scholar 

  • Chirantini A, Valanzano R, Liotta AA, et al.: Hemostatic abnormalities in inflammatory bowel disease. Thromb Res 82:137–146, 1996

    Google Scholar 

  • Koutroubakis IE, Petinaki E, Anagnostopoulou E, et al.: Anti-cardiolipin and anti-β2-glycoprotein I antibodies in patients with inflammatory bowel disease. Dig Dis Sci 43:2507–2512, 1998

    PubMed  CAS  Google Scholar 

  • Saibeni S, Cattaneo M, Vecchi M, et al. Low vitamin B6 levels, a risk factor for thrombosis, in inflammatory bowel disease: role of inflammation and correlation with acute phase reactants. Am J Gastroenterol 98:112–117, 2003

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bas Oldenburg MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oldenburg, B., Van Tuyl, B.A.C., van der Griend, R. et al. Risk Factors for Thromboembolic Complications in Inflammatory Bowel Disease: The Role of Hyperhomocysteinaemia. Dig Dis Sci 50, 235–240 (2005). https://doi.org/10.1007/s10620-005-1588-y

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-005-1588-y

KEY WORDS

Navigation