Activated FVII levels in factor VII Padua (Arg304Gln) coagulation disorder and in true factor VII deficiency: a study in homozygotes and heterozygotes.

Congenital FVII deficiency is usually subdivided into two forms: type I and type II. Type I is characterized by a concomitant deficiency of FVII activity and FVII antigen (true deficiency). Type II is characterized by a discrepancy between FVII activity which is always low and FVII antigen which may be normal, near normal, or reduced. Thromboplastins of different origins may show a discrepant behaviour towards type II FVII deficiencies. The abnormal factor VII present in these forms may, in fact show, different levels of activity, according to the thromboplastin used in the assay system. Typical of these variants is the Arg304Gln mutation (know as FVII Padua). In this variant, FVII level is low when rabbit brain thromboplastin is used, whereas the level is perfectly normal when ox-brain thromboplastin is employed. Intermediate levels are obtained if human placenta or human recombinant is used. Since ox-brain thromboplastin is very sensitive to activated FVII, the normal FVII levels obtained in FVII Padua could be due to abnormally high circulating levels of activated FVII. The purpose of the present paper was to investigate the level of activated FVII present in homozygotes and heterozygotes with FVII Padua. For comparison, a group of patients with type I or 'true' deficiency was also investigated. A group of 21 normal patients served as controls. The activated FVII level found in FVII Padua was 8·4 and 41·0 mU/ml for homozygotes and heterozygotes, respectively. The level found in homozygous true deficiency was unassayable, whereas that found in heterozygotes was 36·2 mU/ml. The level found in the control population was 64·9 mU/ml in agreement with other reports. The low levels of activated FVIIa found in homozygotes with FVII Padua indicate that the normal FVII activity found with ox-brain thromboplastin cannot be attributed to higher than normal circulating levels of FVIIa.

Comparative incidence of thrombosis in reported cases of deficiencies of factors of the contact phase of blood coagulation.

Thrombotic manifestations occurring in patients with coagulation defects have drawn considerable attention during the last decade. It concerned mainly patients with hemophilia, vW disease or FVII deficiency. Occasional reports involved also the deficiencies of the contact phase of blood coagulation, mainly FXII deficiency. The purpose of the present study was to evaluate the comparative incidence of thrombosis in all reported patients with FXII, Prekallikrein and Kininogens deficiencies. Out of the reported 341 cases with these conditions that could be tracked there were 43 cases with thrombosis. More specifically, there were 32 patients with FXII deficiency who also had a thrombotic event (16 arterial and 16 venous). As far as Prekallikrein deficiency is concerned, there were nine cases with thrombosis (five arterial and four venous). Finally, two patients with Total or High molecular weight Kininogen deficiencies had also a thrombotic manifestation (one arterial and one venous). The thrombotic manifestations were M.I. 11 cases; ischemic stroke 9 cases; peripheral arteries 3 cases; deep vein thrombosis with or without pulmonary embolism 17 cases; thrombosis in other veins 3 cases. Congenital or acquired associated prothrombotic risk factors were present in 33 out of 36 cases. In three cases the existence of associated risk factors was excluded whereas in the remaining seven patients no mention is made in this regard. This study clearly indicates that the severe in vitro coagulation defect seen in these conditions does not protect from thrombosis.