title: Treatment of rare factor deficiencies in 2016.
abstract: Rare bleeding disorders (RBDs) are a heterogeneous group of coagulation disorders characterized by fibrinogen, prothrombin, factors V, VII, X, XI, or XIII (FV, FVII, FX, FXI, or FXIII, respectively), and the combined factor V + VIII and vitamin K-dependent proteins deficiencies, representing roughly 5% of all bleeding disorders. They are usually transmitted as autosomal, recessive disorders, and the prevalence of the severe forms could range from 1 case in 500 000 for FVII up to 1 in 2-3 million for FXIII in the general population. Patients affected with RBDs may present a wide range of clinical symptoms, varying from mucocutaneous bleeding, common to all types of RBDs to the most life-threatening symptoms such as central nervous system and gastrointestinal bleeding. Treatment of these disorders is mainly based on the replacement of the deficient factor, using specific plasma-derived or recombinant products. In countries where these facilities are not available, bleedings could be managed using cryoprecipitate, fresh frozen plasma (FFP), or virus-inactivated plasma. Minor bleedings could be managed using antifibrinolytic agents. Recently, 2 novel drugs, recombinant FXIIIA and a plasma-derived FX, have been added to the list of available specific hemostatic factors; only prothrombin and FV deficiencies still remain without a specific product. Novel no-replacement therapies, such as monoclonal antibody anti-tissue factor pathway inhibitor, RNA interference, and a bispecific antibody that is an FVIIIa mimetic, enhancing thrombin generation through different mechanisms, were developed for patients with hemophilia and may in the future be a good therapeutic option also in RBDs.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
authors.forename: Flora
authors.initials: F
authors.lastname: Peyvandi
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Menegatti
mesh_terms: D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D016913:Blood Component Transfusion; D020147:Coagulation Protein Disorders / Q000175:diagnosis / Q000188:drug therapy*; D005169:Factor VIII / Q000627:therapeutic use*; D005340:Fibrinogen / Q000627:therapeutic use*; D006801:Humans; D010949:Plasma; D035583:Rare Diseases
chemical_list: D001779:Blood Coagulation Factors; C026912:cryoprecipitate coagulum; D005169:Factor VIII; D005340:Fibrinogen