Clinical picture and treatment strategies in factor VII deficiency

Factor VII is a trace protein required for normal haemostasis. Deficiency of factor VII comprises a highly heterogeneous disease group. Factor VII deficiency can cause bleeding, in particular if factor VII is extremely low, but a few cases lacking factor VII function entirely or subtotally may not present with a history of bleeding. Bleeding problems are not often reported in patients having a factor VII:C level at 10-15% of normal or more. Bleeding is frequently of mucocutaneous type, but the whole array of haemophilic bleeding may also occur. To control bleeding, during surgery in particular, substitution is required in the severe case of factor VII deficiency, but clinical studies documenting which correctional levels of factor VII:C to aim are lacking. It appears that a critical low level (trough) value at 10-15% may be anticipated, but clear documentation does not exist. Substitution programmes may include plasma or plasma derived factor IX concentrates of lower degrees of purity, so-called prothrombin complex concentrates that also are relatively impure, and pure factor VII concentrates. An alternative is a recombinant factor VIIa molecule. However, this concentrate has not received license in a number of countries. Thrombotic manifestations appear to occur more often than expected in the factor VII deficient patients, some have been linked to the use of impure concentrates, others to preexisting thrombophilic risk factors, but some are unexplained and may bear a relationship to the deficiency state of factor VII itself. Controlled clinical trials are highly warranted in this rare bleeding condition.