Hyperhomocysteinaemia, Coagulation Pathway Activation and Thrombophilia in Patients with Inflammatory Bowel Disease

• Published in: Scandinavian journal of gastroenterology 2002, Vol.37 (1), p.62-67
• Main Authors: Larsen, T. Bjerregaard, Nielsen, J. Nederby, Fredholm, L., Brandslund, I., Munkholm, P., Hey, H.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Blood Coagulation - genetics; Blood Coagulation - physiology; Coagulation; Cross-Sectional Studies; Digestive system; Female; Genotype; Homocysteine; Humans; Hyperhomocysteinemia - complications; Hyperhomocysteinemia - genetics; Hyperhomocysteinemia - physiopathology; Inflammatory Bowel Disease; Inflammatory Bowel Diseases - complications; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - physiopathology; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Middle Aged; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymorphism, Genetic - genetics; Signal Transduction - genetics; Signal Transduction - physiology; Thrombophilia; Thrombophilia - complications; Thrombophilia - genetics; Thrombophilia - physiopathology
• ISSN: 0036-5521; 1502-7708
• DOI: 10.1080/003655202753387374

Background : The 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C → T polymorphism encoding the thermolabile variant is, when present as homozygote type (TT variant), a known genetic cause of mild hyperhomocysteinaemia (HHCY). This polymorphism has been observed in increased numbers in patients with inflammatory bowel disease (IBD). Coagulation and fibrinolysis are activated in patients with active IBD, but it is not known whether raised plasma homocysteine (HCY) found in patients with IBD significantly contributes to this activation. The aim of this study was to investigate if HHCY or presence of the TT variant significantly induces a hypercoagulable state in IBD patients receiving anti-inflammatory therapy during active disease, and to study if genetic determinants for thromboembolic disease are more frequent in these patients. Methods : The study was designed as a cross-sectional study in an outpatient clinic comprising 106 IBD patients receiving anti-inflammatory therapy. Markers of coagulation were measured in order to elucidate whether patients with HHCY or the MTHFR TT variant were hypercoagulant compared with patients with no impairment of HCY metabolism. In addition, markers of inflammation and acute-phase reactants were measured in order to compare activity during active disease and during remission. Genetic determinants of thromboembolic disease in patients with IBD and in relevant controls were investigated in the expectation of a more frequent occurrence of these markers of thrombophilia if hypercoagulability could be a primary or contributory factor in IBD. Results : No significant difference could be found in coagulation activity, acute-phase reactants or inflammatory markers in IBD patients with the TT variant of the 677C → T polymorphism or high (>15 μmol/L) plasma HCY levels, compared with IBD patients with no impairment of HCY metabolism. In patients with IBD, the coagulation activity was significantly increased during active disease compared with a state of remission. As expected, a significant difference regarding interleukin 6, C-reactive protein and erythrocyte sedimentation rate was present in IBD, comparing active disease with a state of remission. No significant complement activation was present in either of the groups or during active disease. Neither of the allele frequencies of genetic determinants for thrombophilia (coagulation factor V 1691G → A (factor V Leiden) and factor II 20210G → A polymorphisms) in the background