The paradoxical association between inherited factor VII deficiency and venous thrombosis

• Published in: Haemophilia : the official journal of the World Federation of Hemophilia Vol. 14; no. 3; pp. 564 - 570
• Main Authors: MARTY, S., BARRO, C., CHATELAIN, B., FIMBEL, B., TRIBOUT, B., REYNAUD, J., SCHVED, J.-F., GIANSILY-BLAIZOT, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2008
• Subjects: Adolescent; Adult; Aged; Antigens - metabolism; antithrombotic prophylaxis; Blood Coagulation Factors - adverse effects; Coagulants - adverse effects; DNA Mutational Analysis; F7 mutations; Factor VII - genetics; Factor VII - metabolism; Factor VII Deficiency - complications; Factor VII Deficiency - genetics; Female; Genotype; Humans; inherited factor VII deficiency; Male; Middle Aged; Mutation - genetics; Phenotype; Risk Factors; Thrombophilia - genetics; thrombotic risk factors; venous thrombosis; Venous Thrombosis - complications; Venous Thrombosis - genetics; Venous Thrombosis - prevention & control
• ISSN: 1351-8216; 1365-2516
• DOI: 10.1111/j.1365-2516.2007.01647.x

Inherited factor VII (FVII) deficiency is considered to be a haemorrhagic disease. Nonetheless, some patients paradoxically present with venous thrombosis. We assessed whether there was a link between phenotype and genotype in seven patients with inherited FVII deficiency and thrombosis (eleven venous thrombotic events). For each patient (FVII:C < 50%), clinical data were collected, aetiological assessment of risk factors for thrombosis was investigated, and direct sequencing of the nine exons and promoter of the FVII gene (F7) was performed. We present the second series ever published on FVII patients with thrombosis. In nine of the eleven thrombotic events, there was at least one classical triggering risk factor; clinical (n = 4), familial antecedent (n = 2), or biological, defined by phospholipid‐binding antibodies or elevated FVIII:C levels (n = 7). In contrast to a previous series, only two events occurred after surgery, performed both with and without replacement therapy. The thrombotic event remained unexplained in one young patient, highlighting the lack of ‘protection’ against venous thrombosis by low FVII:C levels. Genetic mutations were found to be heterogeneous. Among the seven F7 sequence alterations identified in the present study, only two (p.Ala354Val and p.Arg364Gln) have previously been reported in FVII‐deficient patients presenting with venous thrombosis. Our genetic analyses of the F7 mutations in these patients show the complexity of FVII deficiency associated with thrombosis. These data justify a holistic, clinical and biological approach for patients with these specific symptoms. This series also strongly suggest that mild FVII deficiency should not prevent physicians from using antithrombotic prophylaxis in FVII‐deficient patients.