Congenital Factor VII Deficiency with Normal Stuart Activity: Clinical, Genetic and Experimental Observations

The case of a four year old white girl with a bleeding tendency characterized by the spontaneous occurrence of petechiae, ecchymoses and hemarthroses is presented. Laboratory studies indicate a deficiency of factor VII, with normal levels of all other clotting components, and a vascular deficiency possibly related to frequent upper respiratory infection.

Serum from the patient and from four close relatives having reduced levels of factor VII is shown to correct the abnormal thromboplastin generation of Stuart factor-deficient serum. The rate of conversion of prothrombin into thrombin is markedly delayed in the patient’s plasma but essentially normal in that of other family members. The patient’s prothrombin conversion is corrected by the addition of normal or Stuart-deficient plasma. The partial thromboplastin time of the patient is somewhat prolonged.

It is concluded that factor VII deficiency is inherited in this family as an incompletely recessive autosomal characteristic. The penetrance of the deficiency allele in the heterozygous individual appears to be variable. Analyses of the distributions of clotting factor levels in the family and in samples from the normal population indicate that an individual may vary greatly in his clotting factor levels, the average variation being nearly as great as the variation among individuals. The magnitude of the variation among siblings suggests that the penetrance of the factor VII deficiency allele is affected by extrinsic factors and that the observed population variation does not result from the occurrence of multiple alleles. It is suggested that sex may be a factor determining clotting factor levels.

The bleeding of the patient is controlled by transfusion of plasma and by injection of a plasma preparation called ACC-76 (Behringwerke, Germany), the latter followed by a transient elevation of blood factor VII.