Prothrombin was assayed using chromogenic substrate of S-2238 for patients who were being treated with coumarin, for patients who had liver disease, and for patients who had congenital hypoprothrombinemias and dysprothrombinemias. In coumarin therapy and in patients with liver disease the levels found correlated well with the one-stage clotting methods. The same was true for heterozygous and homozygous "true" prothrombin deficiency. In the case of congenital dysprothrombinemias the levels observed with the chromogenic substrate were higher than the clotting counterparts, particularly so in the case of prothrombin Padua. In the latter case the levels observed were always about 100% of normal, as compared with the levels of about 50% of normal found with clotting methods. These data indicate that chromogenic substrates are not always equivalent to "clotting" substrates, namely, that amidolytic activity is not always equivalent to clotting activity. Therefore the two methods cannot be used interchangeably, lest some defects escape detection.

A new factor VII abnormality is presented. The propositus was a 9-yr- old child who presented a mild bleeding tendency characterized by epistaxis and easy bruising. The parents were not consanguineous, but they came from the same area. The laboratory features were mild prolongation of prothrombin time and P.P. test and normal partial thromboplastin and Stypven cephalin clotting times. The Thrombotest was moderately prolonged. Factor VII was 40%-50% of normal using rabbit or human brain thromboplastin, but only 13%-24% using ox brain thromboplastin. Factor VII cross-reacting material (CRM) was about 50% of normal. The father, a paternal aunt, and a paternal cousin showed similar clinical and laboratory findings. The brother of the propositus, the mother, and other members of her family showed about 50% factor VII activity and CRM and were considered to be heterozygotes for true factor VII deficiency. Similar findings were also present in the father and in the brother of the affected cousin. The defect in the propositus seems to consist of a double heterozygosity between abnormal factor VII and heterozygous factor VII true deficiency. The factor VII abnormality appears to consist of abnormal reactivity toward ox brain tissue thromboplastins and appears to be different from previously described factor VII abnormalities. The name factor VII Paudua2 is proposed for this condition.

Two patients with factor VII Padua abnormality were studied during prophylactic administration of factor VII concentrates for tooth extractions. The amounts administered were 15.8 and 17.2 units/kg body weight in 30 and 20 min, respectively. The end infusion factor VII activity levels were 55 and 64%, respectively. Survival times of the exogenous components were 6.5 and 6 h, respectively. Satisfactory hemostasis was obtained in both instances.