Factor VII Padua 2: another factor VII abnormality with defective ox brain thromboplastin activation and a complex hereditary pattern

Abstract

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.

Bleeding manifestations in heterozygotes with congenital FVII deficiency: a comparison with unaffected family members during a long observation period

“…All these patients were studied in Padua during the years 1968-2011. Some were the object of previous papers [15][16][17][18][19][20][21][22], some are unreported. At diagnosis, each patient was matched with an unaffected family member (same gender, age ± 5 years).…”

Molecular defects in CRM+ factor VII deficiencies: modelling of missense mutations in the catalytic domain of FVII

“…Functional FVII variants have been described (Girolami et al, 1977(Girolami et al, , 1979) and a few gene mutations have recently been reported (Chaing & High, 1991;O'Brien et al, 1991;Marchetti et al 1992Marchetti et al , 1993aMillar et al, 1992). The characterization of gene lesions in CRMf FVll deficiency identifies protein residues and regions for comparative structurefunction studies (Kumar et al, 1991;Bjoern et d .…”

Tissue Factor Localization in Non-Human Primate Cerebral Tissue

“…Procoagulant activity in central nervous system tissues is responsible for the acceleration of fibrin formation by brain extracts in in vitro coagulation assays, and the observation of transient disseminated intravascular coagulation (DIC) following acute severe brain injury (1)(2)(3)(4). Partially purified extracts of human, rabbit, and certain other mammalian cerebral tissues accelerate calcium-dependent fibrin formation in plasma (5)(6)(7)(8). Defibrination, consumption of factors V, VIII and X, platelet consumption, and generation of fibrin(ogen) degradation products may accompany significant brain trauma (1,9,10), the severity of which may be predictive of clinical outcome (2).…”