The molecular basis of inherited thrombophilia.
Even though it has been known for centuries that inherited defects of blood coagulation cause lifelong bleeding disorders, the existence of the counterpart, inherited thrombotic disorders, has been appreciated for only a few decades. Inherited thrombophilia can be defined as a genetically determined tendency to venous thromboembolism which characteristically occurs at a young age with no apparent cause and tends to recur. This article reviews the prevalence, biochemical and molecular basis of inherited thrombophilia, describes the main clinical manifestations and provides general guidelines for treatment. It is restricted to the more frequent and well-established causes of thrombophilia: antithrombin, protein C and protein S deficiency; resistance to activated protein C caused by mutations in coagulation factor V; and the gain-of-function mutation of factor II (prothrombin). Other causes of inherited thrombophilia are much rarer, such as dysfibrinogenemia, or not firmly established, such as abnormalities of the fibrinolytic system (plasminogen, histidin-rich glycoprotein) and thrombomodulin.
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, University of Milano, Italy. piermannuccio.mannucci@unimi.it
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D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D011488:Protein Deficiency / Q000150:complications; D013923:Thromboembolism / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D019851:Thrombophilia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D020246:Venous Thrombosis / Q000453:epidemiology / Q000209:etiology / Q000628:therapy