Department of Hematology and Blood Transfusion, School of Allied Medicine, Iran University of Medical Sciences, Tehran 1449614535, Iran. Institute of Experimental Hematology and Transfusion Medicine, University Hospital of Bonn, Sigmund Freud Street 25, 53127 Bonn, Germany.
BACKGROUND Congenital factor (F) VII deficiency is a rare coagulation factor deficiency with an estimated incidence of 1 per 500,000 individuals. Patients with severe FVII deficiency present a broad range of clinical presentations. Alloimmunization against exogenous FVII, as the main challenge of replacement therapy, is an extremely rare phenomenon that is accompanied by a high rate of life-threatening bleeding, that
renders replacement therapy less effective. Due to the importance of the issue, we performed a systematic literature review in order to assess incidence, molecular basis, clinical presentations, and therapeutic challenge and management of inhibitor in congenital FVII deficiency. Strategy of search: This systematic review was performed in accordance with PRISMA guidelines. We performed an English-language literature review in the PubMed, EMBASE, Scopus, and Google Scholar databases, using the following keywords: "factor VII inhibitor", "factor VII inhibitors", "FVII inhibitors", "congenital FVII deficiency", "recombinant factor VII", "anti rFVIIa", "replacement therapy", and "alloantibody". RESULTS Out of 380 patients in the 13 studies, 27 had inhibitor against FVII; 18 were male, 7 were female, while the sex of 2 was not stated. The majority (92%) developed a high-titer inhibitor (Bethesda Unit > 5). All patients had severe FVII deficiency (FVII:C < 10%), and the majority received recombinant FVII prior to inhibitor development (N: 24, 89%). Among ten patients with a detected mutation, three subjects had a common non-sense (30%), and two had a deletion (20%). CONCLUSIONS Inhibitor development is a relatively rare phenomenon seen only in severe FVII deficiency, where it is associated with severe and life-threatening presentations, treatment challenge, and economic burden on the patients and their families.