Subscribe to RSS
DOI: 10.1055/s-0037-1615416
High Prevalence of Hyperhomocysteinemia in Patients with Inflammatory Bowel Disease: a Pathogenic Link with Thromboembolic Complications?
Publication History
Received
11 May 1998
Accepted
14 July 1998
Publication Date:
08 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199804/lookinside/thumbnails/10-1055-s-0037-1615416-1.jpg)
Summary
Background and Aims. Why patients with inflammatory bowel disease are at increased risk for thrombosis is unknown. Since they may have impaired absorption of vitamins that regulate the metabolism of homocysteine, we tested the hypothesis that they have hyper-homocysteinemia, an established risk factor for arterial and venous thrombosis. Methods. The concentrations of total homocysteine (tHcy), folate and cobalamin were measured in blood samples from 61 consecutive patients with inflammatory bowel disease and 183 age- and sex-matched healthy controls. Results. The mean (± S.D.) concentration of plasma tHcy was higher in patients (12.2 ± 7.7 μmol/l) than in controls (10.5 ± 4.6, p = 0.045). Eight patients (13%) had concentrations of tHcy higher than the 95th percentile of distribution among controls, as compared with 9 healthy controls (5%, p = 0.04). The prevalence of folate deficiency was higher in patients (15%) than in controls (5%, p = 0.02). Oral administration of folate, cobalamin and pyridoxine to 15 patients for 30 days decreased their mean tHcy levels from 20.3 ± 9.9 to 9.5 ± 3.4 (p <0.001). Conclusions. In patients with inflammatory bowel disease there is an increased prevalence of hyperhomocysteinemia, which can be corrected by the administration of folate, cobalamin and pyridoxine. The high prevalence of hyperhomocysteinemia may account for the thrombotic risk of IBD patients; whether or not its correction will decrease the thrombotic risk should be tested in properly designed clinical trials.
Presented at the 39th Annual Meeting of the American Society of Hematology, San Diego (CA) December 5-9, 1997, and published in abstract form in Blood 1997; 90 (supplement 1): 398a.
-
References
- 1 Koenigs KP, McPhedran P, Spiro HM. Thrombosis in inflammatory bowel disease.. J Clin Gastroenterology 1987; 9: 617-21.
- 2 Talbot RW, Heppell J, Dozois RR, Beart RW. Vascular complications of inflammatory bowel disease.. Mayo Clin Proc 1986; 61: 140-5.
- 3 Lam A, Borda IT, Inwood MJ, Thompson S. Coagulation studies in ulcerative colitis and Chron’s disease.. Gastroenterology 1975; 68: 245-51.
- 4 Lee JCL, Spittel J, Sauer WG, Owen CA, Thompson JH. Hypercoagulability associated with chronic ulcerative colitis: changes in blood coagulation factors.. Gastroenterology 1968; 54: 76-83.
- 5 Vecchi M, Cattaneo M, de Franchis R, Mannucci PM. Risk of thromboembolic complications in patients with inflammatory bowel disease. Study of hemostasis measurements.. Int J Clin Lab Res 1991; 21: 165-70.
- 6 Aadland E, Odegard OR, Roseth A, Try K. Free portein S deficiency in patients with chronic inflammatory bowel disease.. Scand J Gastroenterol 1992; 27: 957-60.
- 7 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 1989; 30: 188-94.
- 8 Conlan MG, Haire WD, Burnett DA. Prothrombotic abnormalities in inflammatory bowel disease.. Dig Dis Sci 1989; 34: 1089-93.
- 9 Chamoured P, Grunebaum L, Wiesel ML, Freyssinet JM, Duclos B, Cazenave J-P, Baumann R. Prevalence and significance of anticardiolipin antibodies in Crohn’s disease.. Dig Dis Sci 1994; 39: 1501-4.
- 10 Chiarantini E, Valanzano R, Alessandrello Liotta A, Cellai AP, Fedi S, Ilari I, Prisco D, Tonelli F, Abbate R. Hemostatic abnormalities in inflammatory bowel disease.. Thromb Res 1996; 82: 137-46.
- 11 Boushey CJ, Beresford SAA, Omenn GS, Motulski AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes.. JAMA 1995; 274: 1049-57.
- 12 Malinow MR. Homocyst(e)ine and arterial occlusive diseases.. J Intern Med 1994; 236: 603-17.
- 13 McCully KS. Homocysteine and vascular disease.. Nature Med 1996; 2: 386-9.
- 14 Falcon CR, Cattaneo M, Panzeri D, Martinelli I, Mannucci PM. High prevalence of hyperhomocyst(e)inemia in patients with juvenile venous thrombosis.. Arterioscler Thromb 1994; 14: 1080-3.
- 15 den Heijer M, Blom HJ, Gerrits WBJ, Rosendaal FR, Haak HL, Wijermans PW, Bos GMJ. Is hyperhomocysteinemia a risk factor for recurrent venous thrombosis?. Lancet 1995; 345: 882-5.
- 16 Fermo I, ViganòD’Angelo S, Paroni R, Mazzola G, Calori G, D’Angelo A. Prevalence of moderate hyperhomocysteinemia in patients with early-onset venous and arterial occlusive disease.. Ann Intern Med 1995; 123: 747-53.
- 17 den Heijer M, Koster T, Blom HJ, Bos GMJ, Briët E, Reitsma PH, Vanderbrouke JP, Rosendaal FR. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis.. N Engl J Med 1996; 334: 759-62.
- 18 Cattaneo M, Martinelli I, Mannucci PM. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis.. N Engl J Med 1996; 335: 974-5.
- 19 Ridker PM, Hennekens CH, Selhub J, Miletich JP, Malinow MR, Stampfer MJ. Interrelation of hyperhomocyst(e)inemia, factor V Leiden, and risk of future venous thromboembolism.. Circulation 1997; 95: 1777-82.
- 20 Selhub J, Jacques PF, Wilson PWF, Rush D, Rosenberg JH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population.. JAMA 1993; 270: 2693-8.
- 21 Guttormsen AB, Ueland PM, Nesthus I, Nygård O, Schneede J, Vollset SE, Refsum H. Determinants and vitamin responsiveness of intermediate hyperhomocysteinemia (≥40 µ mol/l).. J Clin Invest 1996; 98: 2174-83.
- 22 Hoffbrand AV, Stewart JS, Booth CC, Mollin DL. Folate deficiency in Chron’s disease: incidence, pathogenesis, and treatment.. Br Med J 1968; 2: 71-5.
- 23 Franklin JL, Rosenberg IH. Impaired folic acid absorption in inflammatory bowel disease: effects of salicylazosulfapyridine (azulfidine).. Gastroenterology 1973; 64: 517-25.
- 24 Halsted CH, Gandhi G, Tamura T. Sulfasalazine inhibits the absorption of folates in ulcerative cholitis.. N Engl J Med 1981; 305: 1513-7.
- 25 Zighetti ML, Cattaneo M, Falcon CR, Lombardi R, Harari S, Savoritto S, Mannucci PM. Absence of hyperhomocysteinemia in ten patients with primary pulmonary hypertension.. Thromb Res 1997; 85: 279-82.
- 26 Brattström L. Vitamins and homocysteine-lowering agents.. J Nutr 1996; 126: 1276S-1280S.
- 27 Greengard P. Water-soluble vitamins. The Vitamin B Complex.. In: Goodman LS, Gilman A. eds. The pharmacological basis of therpeutics.. 5th ed. New York:: McMillan Publishing Co., Inc.,; 1975: 1549-63.
- 28 Ubbink JB, Vermaak WJH, van der Merwe A, Becker PJ. Vitamin B12, vitamin B6 and folate nutritional status in men with hyperhomocysteinemia.. Am J Clin Nutr 1993; 57: 47-53.
- 29 Lambert D, Benhayoun S, Adjalla C, Gelot MA, Renkes P, Felden F, Gerard P, Belleville F, Gaucher P, Gueant JL, Nicolas JP. Crohn’s disease and vitamin B12 metabolism.. Dig Dis Sci 1996; 41: 1417-22.
- 30 Herbert V. Drugs effective in megaloblastic anemias. Cobalamin and folic acid.. In: Goodman LS, Gilman A. eds. The pharmacological basis of therpeutics.. 5th ed. New York:: McMillan Publishing Co., Inc.,; 1975: 1324-49.
- 31 Selhub J, Dhar GJ, Rosenberg IH. Inhibition of folate enzymes by sulfasalazine.. J Clin Invest 1978; 61: 221-4.
- 32 Baum CL, Selhub J, Rosenberg IH. Antifolate actions of sulfasalazine on intact lymphocytes.. J Lab Clin Med 1981; 97: 779-84.