Activation of factor VII is the primary event in blood coagulation. Circulating single chain zymogen factor VII has no activity, but upon binding to tissue factor (TF) exposed by vascular injury, it is readily converted to factor Vila (FVIIa). The TF: FVIIa complex in turn activates factor IX, factor X, andautocatalytically, factor VII. Elevated factor VII levels have been associated with increased risk of cardiovascular disease (1, 2) whilst factor VII deficiency is associated with either variable bleeding or more rarely and paradoxically thrombotic manifestations. Synthesised in the liver (3), factor VII is present in plasma at extremely low concentrations (0.5 pg mL1,~ 10nM);(4) and has the shortest half-life of the classical coagulation factors at 3-4 hours. Synthesis of functional factor VII requires vitamin K. For these reasons, acquired factor VII deficiency is very common, since levels of the zymogen fall rapidly in liver disease or on commencement of oral anticoagulation with vitamin K antagonists.

However, this review will focus on the rare inherited deficiencies of factor VII and on what has been learned of the structure and function of this key protein by studying naturally occurring variants. A brief overview of factor VII protein and gene structure, is included for orientation purposes.