**4.2.4 Homocysteine and thrombosis in children**

Venous thrombosis in children occurs at a much lower frequency than in adults and the events are usually provoked by acquired risk factors like sepsis, cancer and central venous catheters. The association of VTE and hyperhomocysteinemia in children has been confirmed in two case control studies (Koch et al., 1999; Kosch et al., 2004).

#### **4.2.5 Hyperhomocysteinemia and pregnancy**

Hyperhomocysteinemia during pregnancy, which is a consequence of perturbations in methionine and/or the folate metabolism, has been implicated in adverse outcomes such as

Hyperhomocysteinemia: Relation to Cardiovascular Disease and Venous Thromboembolism 29

damage. At this time, no clear medical indication exists for women with a history of recurrent pregnancy loss, preeclampsia, placental abruption, and/or small-for-age babies to have homocysteine levels checked, although appropiate clinical research should come with

As with homocysteine, no official guidelines exist as to who should be tested for MTHFR. In the absence of elevated homocysteine levels, MTHFR mutations appear to have no clinical relevance in regard to thrombosis and atherosclerosis. However, in case of elevated homocysteine levels of MTHFR patients the risk for venous thromoembolism increases dramatically. Since treatment can be relatively easy according to diet, one could argue that there is indication to perform MTHFR genetic testing after the homocysteine test shows

Elevated homocysteine concentration has been identified as an independent risk factor for

Results of multiple prospective and case control studies have shown that patients with a moderately elevated plasma homocysteine concentration are more likely to develop venous and arterial thrombosis compared to the control population. Homocysteine seems to promote atherothrombosis by a variety of mechanisms. The precise pathogenic mechanism remains to be confirmed and it is not yet clear whether homocysteine itself or a related metabolite or a cofactor is primarily responsible for the atherothrombogenic effects of hyperhomocysteinemia. However, recent studies indicate that lowering an elevated homocysteine level does decrease the risk of atherosclerosis and blood clots. Until this issue has been more clearly defined, it appears prudent to make an effort to try to lower one's homocysteine levels through supplementation with B vitamins, which is an efficient and

The MTHFR mutations appear to be medically irrelevant, as long as an individual's homocysteine level is normal. Therefore, it should be first the homocysteine level, not the MTHFR genetic status, to be tested in patients with or at risk for blood clots, atherosclerosis,

It is well estabilished that healthly lifestyle lowers homocysteine concentrations. So the most important in everyday life is awareness that the level of homocysteine in blood is strongly influenced by several lifestyle factors such as nutrition, stress, smoking cigarettes, alcohol consumption, or physical inactivity. And therefore, exercise is a commonly recommended lifestyle intervention for individuals at risk for, or diagnosed with, cardio vascular disease. More specifically, we suggest that exercise, mild in aged people, but especially heavy physical activity, exerts its most favorable effect in subjects

The authors wish to thank Dr. Cécil J.W. Meulenberg for proofreading and useful

more evidence for this.

**7. Conclusion** 

elevated levels (Varga et al., 2005).

premature cardiovascular disease.

or pregnancy complications.

with hyperhomocysteinemia.

**8. Acknowledgement** 

suggestions.

safe way to reduce an elevated homocysteine levels.

neural tube defects, preeclampsia, spontaneous abortion, and premature delivery (Dasarathy et al., 2010). This is pertinent as it is believed that placental thrombosis may contribute to the pathogenesis of these conditions (Gatt & Makris, 2007).
