Background-Inflammatory bowel disease (IBD) is associated with an increased incidence of thromboembolic disease. Hyperhomocysteinaemia (hyper-tHcy), a condition associated with the C677T variant of 5,10-methylenetetrahydrofolate reductase (MTHFR), is linked with an increased incidence of thromboembolic disease. Hyper-tHcy has been reported in patients with IBD. Aims-To assess the prevalence of the C677T MTHFR genotype and the contribution of this genotype to hyper-tHcy in patients with IBD. Methods-Patients with established IBD (n=174) and healthy controls (n=273) were studied. DNA samples were genotyped for the MTHFR (C677T) mutation. Subjects were categorised as homozygous for the thermolabile variant (TT), heterozygous for wild type and variant (CT), or homozygous for the wild type (CC). Results-Plasma homocysteine concentrations were significantly higher in patients with IBD than in healthy controls. A total of 17.5% of ulcerative colitis and 16.8% of Crohn's disease patients were homozygous for the C677T variant compared with 7.3% of controls. Homozygosity (TT) for the variant was associated with higher plasma tHcy levels in patients with IBD and in healthy controls. When all subjects who were TT for the variant were excluded, median plasma tHcy was still significantly higher in IBD than controls. Plasma vitamin B 12 levels were lower in patients with IBD irrespective of MTHFR genotype.Conclusions-There is an association between the thermolabile MTHFR C677T variant and IBD. This accounts in part for the raised plasma tHcy found in patients with IBD and may contribute to the increased incidence of thromboembolic complications. All patients with IBD should receive low dose folic acid and vitamin B 12 therapy to protect against the thromboembolic complications of raised tHcy. (Gut 1999;45:389-394)

We assessed the prevalence of von Willebrand's disease (VWD) in patients with objectively confirmed dysfunctional uterine bleeding. A case-control study was designed to include 38 patients with objectively confirmed dysfunctional uterine bleeding and 38 age-matched controls with normal menstrual blood loss (MBL). Menorrhagia was defined as a mean MBL of greater than 80 ml on three consecutive menses as measured by the alkali haematin method. von Willebrand factor antigen, von Willebrand factor activity (VWF:Ac) and factor VIII:C were measured on three serial venous blood samples 1 week apart. VWD was diagnosed in five of 38 (13%) patients with menorrhagia and one of 38 (2.6%) patients with normal menstrual blood loss. The mean VWF:Ac value was significantly reduced in patients with menorrhagia (mean +/- standard deviation, 84.5 +/- 26.7 IU/dl versus 103.9 +/- 34.5 IU/dl; P < 0.01) and this effect persisted after exclusion of patients diagnosed with VWD. Failure to investigate patients for VWD will limit the potential benefits of medical therapies such as tranexamic acid or nasal desmopressin [1-desamino-8-D-arginine vasopressin, (DDAVP)] and, in addition, will lead to an increased risk associated with surgical intervention in patients with undiagnosed VWD.