Twenty-one asymptomatic individuals with a mildly prolonged prothrombin time ( > 2 SD from the prothrombin time of the reference plasma) were found to have a mild isolated factor VII (F VII) defect (a 38.8 U/dl; SD 13.2). Factor VII antigen levels were also found to be reduced (a 45.5 Uidl; SD 7.8) in 13 of them. These figures were compared with those of 50 normals and 28 obligatory heterozygotes for F VII deficiency. The phenotypical behaviors in the propositi were found to be equal to those of the F VII congenital deficiency heterozygotes: the discrepant one (VII') and the nondiscrepant one (VII-'R).
Fifteen families of the propositi could also be studied, totalling 55 additional individuals; in 25 of them (ten pedigrees) a mild F VII deficiency was found showing the same phenotypical features of the corresponding propositi.
We therefore believe that these individuals with mild F VII deficiency can be considered as heterozygotes for the defect, since (1) the other vitamin K-dependent clotting factors were normal; (2) the defect is transmitted throughout the kindred with the same mode of inheritance as F VII congenital deficiency; and (3) F VII:C and F VI1:Ag levels are highly comparable with those of known obligatory heterozygotes for F VII deficiency.
On the grounds of a careful statistical analysis we propose a formula which allows a discrimination between the two phenotypes of the heterozygotes for F VII congenital deficiency.
In addition it is suggested that sensitive tissue thromboplastins should be used to pick up these mild defects.