Evaluation of the nature of mildly prolonged prothrombin times.
Twenty-one asymptomatic individuals with a mildly prolonged prothrombin time (greater than 2 SD from the prothrombin time of the reference plasma) were found to have a mild isolated factor VII (F VII) defect (mean 38.8 U/dl; SD 13.2). Factor VII antigen levels were also found to be reduced (mean 45.5 U/dl; 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 the other vitamin K-dependent clotting factors were normal; the defect is transmitted throughout the kindred with the same mode of inheritance as F VII congenital deficiency; and F VII:C and F VII: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.
D000293:Adolescent; D000328:Adult; D000941:Antigens / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005167:Factor VII / Q000032:analysis / Q000276:immunology; D005168:Factor VII Deficiency / Q000097:blood; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D011517:Prothrombin Time; D013925:Thromboplastin
D000941:Antigens; C042580:factor VII clotting antigen; C031500:factor VII related antigen; D005167:Factor VII; D013925:Thromboplastin