Folic acid thrombosis

Figure 22.6 How various factors increase the risk of atherosclerosis, thrombosis and myocardial infarction. The diagram provides suggestions as to how various factors increase the risk of development of the trio of cardiovascular problems. The factors include an excessive intake of total fat, which increases activity of clotting factors, especially factor VIII an excessive intake of saturated or trans fatty acids that change the structure of the plasma membrane of cells, such as endothelial cells, which increases the risk of platelet aggregation or susceptibility of the membrane to injury excessive intake of salt - which increases blood pressure, as does smoking and low physical activity a high intake of fat or cholesterol or a low intake of antioxidants, vitamin 6 2 and folic acid, which can lead either to direct chemical damage (e.g. oxidation) to the structure of LDL or an increase in the serum level of LDL, which also increases the risk of chemical damage to LDL. A low intake of folate and vitamin B12 also decreases metabolism of homocysteine, so that the plasma concentration increases, which can damage the endothelial membrane due to formation of thiolactone.

In a totally different field, studies were being carried out on children who had a deficiency of methionine synthase and an impaired ability to convert homocysteine to methionine, so that they had increased blood levels of homocysteine. It was noted that these children had an increased incidence of thrombosis in cerebral and coronary arteries. This led to a study which eventually showed that an increased level of homocysteine was a risk factor for coronary artery disease in adults. Since methionine synthase requires the vitamins, folic acid and B12, for its catalytic activity, it has been suggested that an increased intake of these vitamins could encourage the conversion of homocysteine to methionine and hence decrease the plasma level of homocysteine. This is particularly the case for the elderly who are undernourished (see Chapter 15 for a discussion of nutrition in the elderly). 

On the day of admission, the patient had developed a deep venous thrombosis in his right calf, a site not involved in the injury. In investigating the underlying cause of the deep venous thrombosis, serum homocysteine was measured and found to be 17.4 pmol/L (normal is < 14 pmol/I.).To distinguish between folic acid and vitamin B12 deficiencies, a serum methylmalonic acid (MMA) assay was performed it yielded a result of 0.59 pmol/I. MMA (normal is < 0.30 pmol/L). This confirmed the presence of vitamin B12 deficiency, despite a serum B12 concentration that was within the normal range. 

Table 3.1 Folic acid, Bg, B12 and cardiovascular outcomes. This table summarizes all the important double-blind randomized clinical trials with the use of folie acid, Bg and B12 vitamins for cardiovascular disease prevention. 5-MTHF 5-methyl tetrahydrofolate CKD chronic kidney disease CVD cardiovascular disease DVT deep vein thrombosis ESRD end stage renal disease FA folic acid f/u follow-up MI myocardial infarction RR relative risk UA unstable angina.

B vitamins. Among the 13 vitamins, B vitamins are eight water-soluble vitamins (vitamin Bp thiamine vitamin B2 riboflavin vitamin B3 niacin vitamin B5 pantothenic acid vitamin Bg pyridoxine, pyridoxal or pyridoxamine vitamin B7 biotin vitamin B9 folic acid or folate and vitamin B cyanoco-balamin). Folate and vitamins Bg and B12 have joint effects on homocysteine. Cardiovascular disease. Cardiovascular disease (CVD) is a group of disorders of the heart and blood vessels and includes coronary heart disease, cerebrovascular disease, peripheral arterial disease, rheumatic heart disease, congenital heart disease (malformations of heart structure existing at birth) and deep vein thrombosis and pulmonary embolism. 

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