Asymptomatic factor VII deficiency: gene analysis and structure–function relationships

Abstract

Factor VII Padua is a variant form of factor VII deficiency characterized by a prolongation of the prothrombin time (PT), when the assay is performed using rabbit brain thromboplastin. The PT is normal when performed using either human or ox brain thromboplastin reagents, or a recombinant human tissue factor-based thromboplastin. We report a case of an African-American woman with asymptomatic factor VII deficiency, who had a prolonged PT and factor VII activity levels of 5-8% using rabbit brain thromboplastin, but a normal PT and factor VII activity levels when measured using recombinant human brain thromboplastin or tissue factor. The amino acid substitution (R304Q), which gives rise to factor VII Padua, was found in our patient, making this only the fourth African-American case described to date with this mutation. Our report emphasizes the importance of identifying this benign form of factor VII deficiency in order to avoid unnecessary exposure of patients to treatment with either plasma-derived products or recombinant activated factor VII.

Thrombin generation in different cohorts: Evaluation of the haemostatic potential

“…Intermediate values around 30-40% of normal were obtained using human placenta or human recombinant thromboplastin (h-thromboplastin) was used [158]. Those findings have been confirmed by other studies [159,160,161].…”

Worldwide diffusion of FVII Arg304Gln coagulation defect (FVII Padua)*

“…Altogether, 27 proven homozygous patients with the FVII Padua defect, belonging to 21 kindreds, were discovered in the world literature (4–20). At least about 15 additional probable cases but without the molecular biology confirmation were also found (25, 26).…”

“…The personal files concerning the original six homozygotes were reevaluated. Original papers, regardless of the language, were obtained after an extensive Pub Med search, through the collaboration of the Pinali Medical Library of Padua University and through the Courtesy of Acta Med, Sorengo, Switzerland (9–20). Criteria for inclusion were as follows: low level of FVII activity in tests which employed rabbit brain thromboplastins, normal levels while using ox‐brain preparations and normal FVII antigen.…”

Congenital FVII deficiency and thrombotic events after replacement therapy

“…Patients with this mutation (Arg304Gln) are asymptomatic in general or only paucisymptomatic and seldom need substitution therapy. This aspect has been emphasized by several Authors [13,14,30] and is fully shared by the Padua group [15,31]. Finally, the study report underscore once again the need for an accurate diagnosis of the type of FVII defect using thromboplastins of different origin [7,15].…”

“…FVII antigen is normal [7]. After our first description several other cases have been reported in different countries [11][12][13][14]. Bleeding tendency was always reported to be mild or absent.…”