Factor VII Padua: a congenital coagulation disorder due to an abnormal factor VII with a peculiar activation pattern.

A family with a peculiar factor VII defect is presented. The proposita and her daughter presented a coagulation defect characterized by a prolonged rabbit brain thromboplastin prothrombin time, a normal partial thromboplastin clotting time and a normal Stypven-Cephalin clotting time. The PP test and Normotest, which are other tests employing rabbit brain thromboplastin, were also clearly prolonged. However, Thrombotest and other ox-brain thromboplastin preparations yielded perfectly normal clotting times. Factor VII activity was about 9% according to rabbit brain and lung thromboplastin times, but it was 105% of normal with ox-brain thromboplastin times. Thromboplastins obtained from human brain and human placenta and from simian brain gave intermediate levels. The neutralization test using an anti-factor VII antiserum revealed normal factor VII antigen levels in all instances. Bleeding manifestations were mild and characterized by occasional epistaxis and easy bruising. The subjects appear to be homozygotes for an abnormal factor VII. Several other members of the family, including the husband of the proposita, are heterozygotes for the same abnormality. The factor VII abnormality seems to consist of a faulty activation by certain thromboplastins (rabbit brain or rabbit brain and lung) and in a normal activation by ox-brain thromboplastins. The patients live in an isolated valley of the northern part of the Venetian region where intermarriages among the inhabitants have been frequent over the past centuries. This may justify the peculiar hereditary pattern observed in the proposita and her daughter, in spite of the fact that no apparent consanguinity was evident. The term 'factor VII Padua' is proposed to define this condition.