Tissue factor interactions with factor VII: measurement and clinical significance of factor VIIa in plasma

Certain epidemiological studies have implicated elevated factor VII coagulant activity as a risk factor for ischaemia heart disease. However, progress in understanding the clinical significance of elevated plasma factor VII levels has been hampered by: (1) differences between laboratories in the methodology for measuring factor VII; (2) the existence of multiple forms of factor VII in plasma (i.e. factor VIIa, zymogen factor VII, and a possible phospholipase-sensitive form of factor VII); (3) the resulting uncertainty regarding what is actually being measured in factor VII coagulant assays. Recent mutagenesis studies of tissue factor (the obligate protein cofactor for factor VIIa) have led to new assay technologies capable of quantifying trace levels of plasma factor VIIa without interference from zymogen factor VII. This review article focuses on the current status of measurement of plasma factor VII/VIIa levels and the relationship between various plasma forms of factor VII and risk of thrombotic disease.