Molecular coagulation and thrombophilia

Chapter 15 Molecular coagulation and thrombophilia Björn Dahlbäck, Björn Dahlbäck Department of Translational Medicine, Lund University, University Hospital, Malmö, SwedenSearch for more papers by this authorAndreas Hillarp, Andreas Hillarp Department of Medical Biochemistry, Oslo University Hospital, Oslo, NorwaySearch for more papers by this author Björn Dahlbäck, Björn Dahlbäck Department of Translational Medicine, Lund University, University Hospital, Malmö, SwedenSearch for more papers by this authorAndreas Hillarp, Andreas Hillarp Department of Medical Biochemistry, Oslo University Hospital, Oslo, NorwaySearch for more papers by this author Book Editor(s):Drew Provan, Drew ProvanSearch for more papers by this authorHillard M. Lazarus, Hillard M. LazarusSearch for more papers by this author First published: 08 March 2024 https://doi.org/10.1002/9781394180486.ch15 AboutPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShareShare a linkShare onEmailFacebookTwitterLinkedInRedditWechat Summary In healthy individuals, a delicate balance between pro- and anticoagulant systems ensures efficient hemostasis and an open vascular system. As sites of vascular damage, a series of procoagulant reactions take place, which are carefully controlled by several anticoagulant proteins. Circumstantial and genetic risk factors increase the risk of venous thrombosis. Circumstantial risk factors are usually short in duration, whereas the genetic risk factors are lifelong. The most common genetic risk factor causing thrombophilia is Factor V Leiden (FVL), a point mutation which eliminates one of the cleave sites for the anticoagulant activated protein C (APC), thus causing APC resistance. Other relatively common thrombophilic risk factors include deficiencies of antithrombin, protein C, and protein S. In this review, we will outline the molecular mechanisms of the pro- and anticoagulant pathways and the molecular genetics of thrombophilia, which is a classical example of a multigenetic disease. Further reading Blood coagulation: introduction and regulation Camire , R., M. ( 2016 ). Rethinking events in the haemostatic process: role of factor V and TFPI . Haemophilia 22 ( Suppl 5 ): 3 – 8 . 10.1111/hae.13004 PubMedWeb of Science®Google Scholar Dahlbäck , B. ( 2005 ). Blood coagulation and its regulation by anticoagulant pathways: genetic pathogenesis of bleeding and thrombotic diseases . J. Intern. Med. 257 : 209 – 223 . 10.1111/j.1365-2796.2004.01444.x CASPubMedWeb of Science®Google Scholar Dahlbäck , B. and Villoutreix , B., O. ( 2005 ). Regulation of blood coagulation by the protein C anticoagulant pathway: novel insights into structure–function relationships and molecular recognition . Arterioscler. Thromb. Vasc. Biol. 25 : 1311 – 1320 . 10.1161/01.ATV.0000168421.13467.82 CASPubMedWeb of Science®Google Scholar Dahlbäck , B. ( 2016 ). Pro- and anticoagulant properties of factor V in pathogenesis of thrombosis and bleeding disorders . Int. J. Lab. Hematol. 38 ( Suppl 1 ): 4 – 11 . 10.1111/ijlh.12508 PubMedWeb of Science®Google Scholar Dahlbäck , B. ( 2017 ). Novel insights into the regulation of coagulation by factor V isoforms, tissue factor pathway inhibitoralpha, and protein S . J. Thromb. Haemost. 15 : 1241 – 1250 . 10.1111/jth.13665 CASPubMedWeb of Science®Google Scholar Dahlbäck , B. ( 2023 , 2023). Natural anticoagulant discovery, the gift that keeps on giving: finding FV-short . J. Thromb. 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