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Food Lipids: Chemistry, Nutrition, and Biotechnology

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Figure 14 Schematic representation of the coagulation cascade. When factor VII contacts<br />

a tissue factor, expressed, for example, after vessel injury or inflammation, factor VII is rapidly<br />

converted to factor VIIa. The complex of factor VIIa with tissue factor initiates a cascade of<br />

reactions, which ultimately results—after cleavage of fragment 1�2—in the conversion prothrombin<br />

into thrombin. Thrombin cleaves fibrinogen into fibrin, which stabilizes a thrombus.<br />

Tissue factor pathway inhibitor (TFPI) <strong>and</strong> antithrombin III inhibit the coagulation cascade.<br />

are normally present in large excess in the blood, <strong>and</strong> only a small percentage is<br />

converted to active enzymes under in vivo situations. Nowadays other assays are<br />

also available, which reflect actual in vivo coagulation. The plasma fragment 1�2<br />

concentration reflects the amount of prothrombin actually converted to thrombin,<br />

while fibrinopeptides A <strong>and</strong> B concentrations reflect the conversion of fibrinogen to<br />

fibrin. However, in healthy subjects, concentrations of most of these markers are<br />

very low <strong>and</strong> just above detection limits, which sometimes make it difficult to implement<br />

them in dietary studies.<br />

Many methods are available to measure factor VII. In many studies, factor VII<br />

is measured with a coagulant assay (factor VII coagulant activity). Factor VII activity,<br />

however, is measured with a two-step chromogenic assay, which depends on the rate<br />

of generation of factor Xa from factor X by factor VIIa. Both methods may give<br />

different results <strong>and</strong> do not differentiate between factor VIIa <strong>and</strong> factor VII antigen<br />

concentrations [70].<br />

Fibrinogen concentrations are usually measured with the method of Clauss [72].<br />

A fixed surplus of thrombin is added to diluted platelet-poor plasma samples, the<br />

clotting time recorded, <strong>and</strong> the fibrinogen concentration read from a calibrator curve.<br />

2. Coagulation <strong>and</strong> Coronary Heart Disease<br />

Long-term prospective epidemiological studies have consistently reported that in<br />

healthy males factor VII coagulant activity <strong>and</strong> fibrinogen concentrations were higher<br />

in subjects who developed cardiovascular diseases at a later stage of the study. Factor<br />

VII coagulant activity was particularly associated with an increased risk of dying<br />

Copyright 2002 by Marcel Dekker, Inc. All Rights Reserved.

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