Case 13: Deep leg vein thrombosis due to acquired thrombophilia – Hyperhomocysteinemia caused by hitherto undiagnosed celiac disease

Abstract

Today hyperhomocysteinemia is a well known and important risk factor for arteriosclerotic vascular and venous thromboembolic disease with a high prevalence in the general population. Elevation of plasma homocysteine levels are caused either by genetic defects in the enzymes involved in homocysteine metabolism or by nutritional deficiencies of vitamin cofactors (folate, vitamin B12, vitamin B6). A number of other factors may influence homocysteine metabolism, such as several disease states and medications. It has been demonstrated, that supplementation of folate, vitamin B12, or vitamin B6 can correct mild and moderate hyperhomocysteinemia.

Risk of thromboembolism in 14 000 individuals with coeliac disease

“…Several case‐reports (Zenjari et al , 1995; Grigg, 1999; Kremer Hovinga et al , 1999; Andres et al , 2000; Manzano et al , 2002; Gabrielli et al , 2003) suggest an increased risk of VTE in CD. An Austrian study failed to find an increased risk of VTE in CD [odds ratio (OR) = 0·4; 95% confidence interval (CI) = 0·1–2·5] (Miehsler et al , 2004); this may be because of low power as this study was primarily designed to investigate VTE in inflammatory bowel disease and not in CD.…”

The thrombophilic network of autoantibodies in celiac disease

“…The pathophysiology of the thromboembolic phenomena associated with CD [10-26] represents a puzzle with multiple constituents: hyperhomocysteinemia; B12 and\or folate deficiency; methylenetetrahydrofolate reductase mutations; the high homology between blood coagulation factor XIII and tTG; and protein C and S deficiency due to vitamin K deficiency [21-26,54]. The present study unravels a series of autoantibodies, aPL, aPT and mainly aPS/PT, that form part of this puzzle and are suggested to play a pathogenic role in the thrombogenicity of CD.…”

“…There is an increase risk of stroke in adults and children with CD [10-15]. Thrombophilia, pregnancy loss, deep vein thrombosis, small bowel infarction, atrial fibrillation, Budd-Chiari syndrome, portal and splenic vein thrombosis, and cardiovascular disease have been described [16-21]. Even the onset of the disease may be due to a thrombotic event [11,17,21].…”

“…Thrombophilia, pregnancy loss, deep vein thrombosis, small bowel infarction, atrial fibrillation, Budd-Chiari syndrome, portal and splenic vein thrombosis, and cardiovascular disease have been described [16-21]. Even the onset of the disease may be due to a thrombotic event [11,17,21]. Hyperhomocysteinemia with related vitamin deficiency in untreated CD, the frequency of methylenetetrahydrofolate reductase variants and the high homology between factor XIII and tTG add to the hypercoagulable status in patients [21-26].…”

“…Even the onset of the disease may be due to a thrombotic event [11,17,21]. Hyperhomocysteinemia with related vitamin deficiency in untreated CD, the frequency of methylenetetrahydrofolate reductase variants and the high homology between factor XIII and tTG add to the hypercoagulable status in patients [21-26]. …”