3.3.1.3.1 MTHFR polymorphism 677C/T

The rare condition of classical homocystinuria is most often caused by a deficiency of either cystathionine-ß-synthetase or 5-methyltetrahydrofolate-homocysteine-methyltransferase and correlates with frequent TE due to severe homocysteinemia causing endothelial cell damage. The activity of 5-methyl tetrahydrofolate-homocysteine-methyltransferase in turn depends on the availability of 5-methyl-tetrahydrofolate, regulated by 5, 10-methyl tetrahydrofolate-reductase (MTHFR). A common thermolabile MTHFR-variant (MTHFR, 677C>T) correlates with a slightly elevated level of homocysteine. Although repeatedly claimed in many studies, this variant does not seem to be an independent risk factor for TE.

### 3.3.1.3.2 Lipoprotein (a)

Lipoprotein (a) is considered a significant venous and arterial risk factor for TE in children.(Nowak - Gottl et al, 1999; Nowak - Gottl et al, 1999) However, other reports could not confirm these findings.(Revel - Vilk et al, 2003) Levels of Lp(a), though genetically determined, vary considerably among different populations. Lp(a) has structural homology to plasminogen, suggesting a possible competitive mechanism of Lp(a) in fibrinolysis. However, the lack of correlation between severe plasminogen deficiency and TE speaks against this hypothesis.
