title: Classic thrombophilic gene variants.
abstract: Thrombophilia is defined as a condition predisposing to the development of venous thromboembolism (VTE) on the basis of a hypercoagulable state. Over the past decades, great advances in the pathogenesis of VTE have been made and nowadays it is well established that a thrombophilic state may be associated with acquired and/or inherited factors. The rare loss-of-function mutations of the genes encoding natural anticoagulant proteins (i. e. protein C, protein S and antithrombin) and the more common gain-of-function polymorphisms factor V Leiden and prothrombin G20210A are the main genetic determinants of thrombophilia. In addition, non-O blood group has been consistently demonstrated to be the most frequent inherited marker of an increased risk of VTE. The mechanism role of these inherited thrombophilia markers will be discussed in this narrative review.
authors.affiliation: Pier Mannuccio Mannucci, Scientific Direction, IRCCS Ca' Granda Maggiore Policlinico Hospital Foundation, Milan, Italy, E-mail: pm.mannucci@policlinico.mi.it.
authors.forename: Pier Mannuccio
authors.initials: PM
authors.lastname: Mannucci
authors.forename: Massimo
authors.initials: M
authors.lastname: Franchini
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D005165:Factor V / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D011110:Polymorphism, Genetic; D011516:Prothrombin / Q000235:genetics*; D012307:Risk Factors; D019851:Thrombophilia / Q000175:diagnosis / Q000235:genetics*; D054556:Venous Thromboembolism / Q000175:diagnosis / Q000235:genetics*
chemical_list: D000991:Antithrombins; D015415:Biomarkers; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin
keywords: ABO blood group; Inherited thrombophilia; factor V Leiden; natural anticoagulants; prothrombin mutation