title: Rare bleeding disorders-old diseases in the era of novel options for therapy.
abstract: Rare diseases are defined as life-threatening or chronically debilitating diseases with a prevalence of less than one per 2000 according to the European Union or one per 1250 according to the USA. Congenital rare bleeding disorders RBD are reported in most populations, with incidence varying from 1 in 5000 (Hemophilia A), 1:30,000 (Hemophilia B) to much rarer (1:500,000 for FVII deficiency, 1-3 million for Prothrombin or FXIII deficiency). Acquired Hemophilia A is also a rare bleeding disorder with estimated frequency of 1 in million. Most RBDs are inherited as autosomal recessive (AR); however, heterozygous carriers with varying degrees of corresponding factor deficiency may render an unpredictable propensity for bleeding. In patients with bleeding symptoms, laboratory assessment and especially molecular techniques currently enable accurate diagnosis and may provide tools for prenatal and family counseling. Currently hemostasis control is mainly based upon replacement of the missing coagulation factors (unless presence of inhibitors renders it impossible), however future gene therapy and disruptive, non-replacement alternatives may be promising for patients with RBD.
authors.affiliation: The Israeli National Hemophilia Center and Thrombosis Institute, Sheba Medical Center, Tel Hashomer, and the Sackler faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Tami
authors.initials: T
authors.lastname: Livnat
authors.affiliation: The Israeli National Hemophilia Center and Thrombosis Institute, Sheba Medical Center, Tel Hashomer, and the Sackler faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Assaf Arie
authors.initials: AA
authors.lastname: Barg
authors.affiliation: The Israeli National Hemophilia Center and Thrombosis Institute, Sheba Medical Center, Tel Hashomer, and the Sackler faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Sarina
authors.initials: S
authors.lastname: Levy-Mendelovich
authors.affiliation: The Israeli National Hemophilia Center and Thrombosis Institute, Sheba Medical Center, Tel Hashomer, and the Sackler faculty of Medicine, Tel Aviv University, Israel. Electronic address: Gili.kenet@sheba.health.gov.il.
authors.forename: Gili
authors.initials: G
authors.lastname: Kenet
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000627:therapeutic use; D020147:Coagulation Protein Disorders / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D015316:Genetic Therapy / Q000379:methods; D006470:Hemorrhage / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D006801:Humans; D035583:Rare Diseases / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy
chemical_list: D001779:Blood Coagulation Factors
keywords: Coagulation; Factor replacement; Gene therapy; Hemophilia; Rare bleeding disorders