{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:51:11Z","timestamp":1787165471989,"version":"build-2736575974"},"reference-count":140,"publisher":"Georg Thieme Verlag KG","issue":"06","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hamostaseologie"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Thrombophilia leads to an increased risk of venous thromboembolism. Widely accepted risk factors for thrombophilia comprise deficiencies of protein C, protein S, and antithrombin, as well as the factor V \u201cLeiden\u201d mutation, the prothrombin G20210A mutation, dysfibrinogenemia, and, albeit less conclusive, increased levels of factor VIII. Besides these established markers of thrombophilia, risk factors of unclear significance have been described in the literature. These inherited risk factors include deficiencies or loss-of-activity of the activity of ADAMTS13, heparin cofactor II, plasminogen, tissue factor pathway inhibitor (TFPI), thrombomodulin, protein Z (PZ), as well as PZ-dependent protease inhibitor. On the other hand, thrombophilia has been linked to the gain-of-activity, or elevated levels, of \u03b12-antiplasmin, angiotensin-converting enzyme, coagulation factors IX (FIX) and XI (FXI), fibrinogen, homocysteine, lipoprotein(a), plasminogen activator inhibitor-1 (PAI-1), and thrombin-activatable fibrinolysis inhibitor (TAFI). With respect to the molecular interactions that may influence the thrombotic risk, more complex mechanisms have been described for endothelial protein C receptor (EPCR) and factor XIII (FXIII) Val34Leu. With focus on the risk for venous thrombosis, the present review aims to give an overview on the current knowledge on the significance of the aforementioned markers for thrombophilia screening. According to the current knowledge, there appears to be weak evidence for a potential impact of EPCR, FIX, FXI, FXIII Val34Leu, fibrinogen, homocysteine, PAI-1, PZ, TAFI, and TFPI on the thrombotic risk.<\/jats:p>","DOI":"10.1055\/s-0042-1757562","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T23:30:11Z","timestamp":1671751811000},"page":"370-380","source":"Crossref","is-referenced-by-count":14,"title":["Markers of Hereditary Thrombophilia with Unclear Significance"],"prefix":"10.1055","volume":"42","author":[{"given":"Ulrich J.","family":"Sachs","sequence":"additional","affiliation":[{"name":"Department of Thrombosis and Haemostasis, Giessen University Hospital, Giessen, Germany"},{"name":"Institute for Clinical Immunology, Transfusion Medicine and Haemostasis, Justus Liebig University, Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette","family":"Kirsch-Altena","sequence":"additional","affiliation":[{"name":"Department of Thrombosis and Haemostasis, Giessen University Hospital, Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute for Experimental Haematology and Transfusion Medicine, Bonn University Hospital, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2022,12,22]]},"reference":[{"issue":"08","key":"ref1","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1038\/s41591-019-0492-5","article-title":"Genome-wide association study of peripheral artery disease in the Million Veteran Program","volume":"25","author":"D Klarin","year":"2019","journal-title":"Nat Med"},{"issue":"19","key":"ref2","doi-asserted-by":"crossref","first-page":"e012877","DOI":"10.1161\/JAHA.119.012877","article-title":"Inherited thrombophilia and the risk of arterial ischemic stroke: a systematic review and meta-analysis","volume":"8","author":"T Chiasakul","year":"2019","journal-title":"J Am Heart Assoc"},{"issue":"05","key":"ref3","first-page":"885","article-title":"Classic thrombophilic gene variants","volume":"114","author":"P M Mannucci","year":"2015","journal-title":"Thromb Haemost"},{"issue":"01","key":"ref4","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1055\/s-0039-1677840","article-title":"Laboratory diagnostics in thrombophilia","volume":"39","author":"B Linnemann","year":"2019","journal-title":"Hamostaseologie"},{"issue":"08","key":"ref5","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s10654-013-9825-8","article-title":"Risk of venous thromboembolism associated with single and combined effects of Factor V Leiden, prothrombin 20210A and methylenetetrahydrofolate reductase C677T: a meta-analysis involving over 11,000 cases and 21,000 controls","volume":"28","author":"B Simone","year":"2013","journal-title":"Eur J Epidemiol"},{"key":"ref6","first-page":"I9","article-title":"Risk factors for venous thromboembolism","volume":"107","author":"F A Anderson Jr","year":"2003","journal-title":"Circulation"},{"issue":"06","key":"ref7","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.sbi.2013.10.006","article-title":"New insights into the structure and function of the plasminogen\/plasmin system","volume":"23","author":"R HP Law","year":"2013","journal-title":"Curr Opin Struct Biol"},{"issue":"01","key":"ref8","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3390\/ijms23010337","article-title":"The plasminogen-activator plasmin system in physiological and pathophysiological angiogenesis","volume":"23","author":"A A Ismail","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"02","key":"ref9","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1055\/s-0036-1586227","article-title":"Plasmin: a modulator of immune function","volume":"43","author":"D F Draxler","year":"2017","journal-title":"Semin Thromb Hemost"},{"issue":"02","key":"ref10","doi-asserted-by":"crossref","first-page":"e218","DOI":"10.1055\/s-0038-1660505","article-title":"Effects of plasmin on von Willebrand factor and platelets: a narrative review","volume":"2","author":"L N van der Vorm","year":"2018","journal-title":"TH Open"},{"issue":"09","key":"ref11","doi-asserted-by":"crossref","first-page":"5262","DOI":"10.3390\/ijms23095262","article-title":"The role of fibrinolytic system in health and disease","volume":"23","author":"H C Kwaan","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"03","key":"ref12","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1097\/MBC.0b013e32808738b4","article-title":"Blood inhibitory capacity toward exogenous plasmin","volume":"18","author":"A Banbula","year":"2007","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"09","key":"ref13","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1161\/01.ATV.20.9.2156","article-title":"Thrombin-activatable fibrinolysis inhibitor antigen levels and cardiovascular risk factors","volume":"20","author":"I Juhan-Vague","year":"2000","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"03","key":"ref14","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1182\/blood-2004-08-3253","article-title":"Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis","volume":"105","author":"T Lisman","year":"2005","journal-title":"Blood"},{"issue":"01","key":"ref15","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1182\/blood-2010-02-267740","article-title":"Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1","volume":"116","author":"M E Meltzer","year":"2010","journal-title":"Blood"},{"issue":"03","key":"ref16","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1055\/s-2007-996099","article-title":"Homozygous type I plasminogen deficiency","volume":"23","author":"A M Mingers","year":"1997","journal-title":"Semin Thromb Hemost"},{"issue":"12","key":"ref17","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1111\/j.1538-7836.2007.02776.x","article-title":"Plasminogen deficiency","volume":"5","author":"V Schuster","year":"2007","journal-title":"J Thromb Haemost"},{"issue":"02","key":"ref18","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1055\/s-0038-1650541","article-title":"Genetic diagnosis of dysplasminogenemia: detection of an Ala601-Thr mutation in 118 out of 125 families and identification of a new Asp676-Asn mutation","volume":"76","author":"S Tsutsumi","year":"1996","journal-title":"Thromb Haemost"},{"issue":"15","key":"ref19","doi-asserted-by":"crossref","first-page":"10739","DOI":"10.1016\/S0021-9258(18)82047-6","article-title":"The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells","volume":"268","author":"S J Dawson","year":"1993","journal-title":"J Biol Chem"},{"issue":"06","key":"ref20","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1160\/TH06-12-0745","article-title":"Association between the plasminogen activator inhibitor-1 4G\/5G polymorphism and venous thrombosis. A meta-analysis","volume":"97","author":"A E Tsantes","year":"2007","journal-title":"Thromb Haemost"},{"issue":"07","key":"ref21","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1515\/cclm-2013-1124","article-title":"The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI-1 4G\/5G polymorphism, and myocardial infarction: a Mendelian randomization meta-analysis","volume":"52","author":"G K Nikolopoulos","year":"2014","journal-title":"Clin Chem Lab Med"},{"issue":"05","key":"ref22","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1097\/MBC.0b013e3281ec4eee","article-title":"Plasminogen activator inhibitor-1 4G\/5G polymorphism and risk of ischemic stroke: a meta-analysis","volume":"18","author":"A E Tsantes","year":"2007","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"06","key":"ref23","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/0049-3848(83)90059-2","article-title":"Fibrinolytic activity in plasma and deep vein thrombosis after major abdominal surgery","volume":"32","author":"G Mellbring","year":"1983","journal-title":"Thromb Res"},{"issue":"03","key":"ref24","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1055\/s-0038-1660104","article-title":"Postoperative changes in the plasmatic levels of tissue-type plasminogen activator and its fast-acting inhibitor\u2013relationship to deep vein thrombosis and influence of prophylaxis","volume":"54","author":"J A P\u00e1ramo","year":"1985","journal-title":"Thromb Haemost"},{"issue":"03","key":"ref25","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1053\/beha.1999.0034","article-title":"Fibrinolysis and thrombosis","volume":"12","author":"N A Booth","year":"1999","journal-title":"Best Pract Res Clin Haematol"},{"issue":"07","key":"ref26","doi-asserted-by":"crossref","first-page":"3670","DOI":"10.3390\/ijms22073670","article-title":"Thrombin activatable fibrinolysis inhibitor (TAFI): an updated narrative review","volume":"22","author":"M Sillen","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"09","key":"ref27","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1182\/blood.V95.9.2855.009k02_2855_2859","article-title":"Thrombin activatable fibrinolysis inhibitor and the risk for deep vein thrombosis","volume":"95","author":"N H van Tilburg","year":"2000","journal-title":"Blood"},{"issue":"10","key":"ref28","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1182\/blood-2003-10-3422","article-title":"Thrombin-activatable fibrinolysis inhibitor and the risk for recurrent venous thromboembolism","volume":"103","author":"S Eichinger","year":"2004","journal-title":"Blood"},{"issue":"01","key":"ref29","first-page":"38","article-title":"Absolute risk of venous and arterial thromboembolism in thrombophilic families is not increased by high thrombin-activatable fibrinolysis inhibitor (TAFI) levels","volume":"100","author":"N Folkeringa","year":"2008","journal-title":"Thromb Haemost"},{"issue":"12","key":"ref30","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1194\/jlr.P094763","article-title":"Potent reduction of plasma lipoprotein (a) with an antisense oligonucleotide in human subjects does not affect ex vivo fibrinolysis","volume":"60","author":"M B Boffa","year":"2019","journal-title":"J Lipid Res"},{"issue":"01","key":"ref31","doi-asserted-by":"crossref","first-page":"e48","DOI":"10.1161\/ATV.0000000000000147","article-title":"Lipoprotein(a): a genetically determined, causal, and prevalent risk factor for atherosclerotic cardiovascular disease: a scientific statement from the American Heart Association","volume":"42","author":"G Reyes-Soffer","year":"2022","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"06","key":"ref32","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1055\/s-0036-1598002","article-title":"Lipoprotein(a) as a risk factor for venous thromboembolism: a systematic review and meta-analysis of the literature","volume":"43","author":"F Dentali","year":"2017","journal-title":"Semin Thromb Hemost"},{"issue":"03","key":"ref33","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1080\/14017431.2019.1612087","article-title":"Lipoprotein(a) is not associated with venous thromboembolism risk","volume":"53","author":"S K Kunutsor","year":"2019","journal-title":"Scand Cardiovasc J"},{"issue":"08","key":"ref34","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.jacc.2012.01.078","article-title":"Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism","volume":"60","author":"A Helgadottir","year":"2012","journal-title":"J Am Coll Cardiol"},{"issue":"07","key":"ref35","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1161\/ATVBAHA.112.248765","article-title":"Genetic evidence that lipoprotein(a) associates with atherosclerotic stenosis rather than venous thrombosis","volume":"32","author":"P R Kamstrup","year":"2012","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"20","key":"ref36","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1161\/CIRCULATIONAHA.120.046397","article-title":"The effect of PCSK9 (proprotein convertase subtilisin\/kexin type 9) inhibition on the risk of venous thromboembolism","volume":"141","author":"N A Marston","year":"2020","journal-title":"Circulation"},{"issue":"12","key":"ref37","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1111\/jth.15068","article-title":"Inherited and acquired thrombophilia in adults with retinal vascular occlusion: a systematic review and meta-analysis","volume":"18","author":"G F Romiti","year":"2020","journal-title":"J Thromb Haemost"},{"issue":"07","key":"ref38","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1097\/HJH.0000000000002057","article-title":"Hypertension and multiple cardiovascular risk factors increase the risk for retinal vein occlusions: results from the Gutenberg Retinal Vein Occlusion Study","volume":"37","author":"K A Ponto","year":"2019","journal-title":"J Hypertens"},{"issue":"03","key":"ref39","doi-asserted-by":"crossref","first-page":"e295","DOI":"10.1055\/s-0041-1732803","article-title":"Role of increased lipoprotein (a) in retinal vein occlusion: a systematic review and meta-analysis","volume":"5","author":"F Paciullo","year":"2021","journal-title":"TH Open"},{"issue":"05","key":"ref40","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1161\/01.ATV.21.5.731","article-title":"Elevated factor VIII levels and the risk of thrombosis","volume":"21","author":"P W Kamphuisen","year":"2001","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"07","key":"ref41","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1056\/NEJM200008173430702","article-title":"High plasma levels of factor VIII and the risk of recurrent venous thromboembolism","volume":"343","author":"P A Kyrle","year":"2000","journal-title":"N Engl J Med"},{"issue":"02","key":"ref42","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1111\/jth.15163","article-title":"High risk of venous thromboembolism after orthopedic surgery in patients with thrombophilia","volume":"19","author":"R Zambelli","year":"2021","journal-title":"J Thromb Haemost"},{"issue":"12","key":"ref43","doi-asserted-by":"crossref","first-page":"3631","DOI":"10.1182\/blood-2004-03-1042","article-title":"A shortened activated partial thromboplastin time is associated with the risk of venous thromboembolism","volume":"104","author":"A Tripodi","year":"2004","journal-title":"Blood"},{"issue":"10","key":"ref44","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1056\/NEJM200003093421004","article-title":"High levels of coagulation factor XI as a risk factor for venous thrombosis","volume":"342","author":"J CM Meijers","year":"2000","journal-title":"N Engl J Med"},{"issue":"14","key":"ref45","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1182\/blood-2009-05-219915","article-title":"Coagulation factors IX through XIII and the risk of future venous thrombosis: the longitudinal investigation of thromboembolism etiology","volume":"114","author":"M Cushman","year":"2009","journal-title":"Blood"},{"issue":"11","key":"ref46","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1002\/ajh.24168","article-title":"Prospective study of circulating factor XI and incident venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE)","volume":"90","author":"A R Folsom","year":"2015","journal-title":"Am J Hematol"},{"issue":"10","key":"ref47","first-page":"1068","article-title":"Co-segregation of thrombophilic disorders in factor V Leiden carriers; the contributions of factor VIII, factor XI, thrombin activatable fibrinolysis inhibitor and lipoprotein(a) to the absolute risk of venous thromboembolism","volume":"87","author":"E J Libourel","year":"2002","journal-title":"Haematologica"},{"issue":"02","key":"ref48","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1160\/th15-06-0459","article-title":"F11 is associated with recurrent VTE in women. A prospective cohort study","volume":"115","author":"M Bruzelius","year":"2016","journal-title":"Thromb Haemost"},{"issue":"06","key":"ref49","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1097\/MBC.0000000000000753","article-title":"Venous thromboembolism risk associated with ABO, F11 and FGG loci","volume":"29","author":"L Manco","year":"2018","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"12","key":"ref50","doi-asserted-by":"crossref","first-page":"3678","DOI":"10.1182\/blood.V95.12.3678.012k45_3678_3682","article-title":"High levels of factor IX increase the risk of venous thrombosis","volume":"95","author":"A van Hylckama Vlieg","year":"2000","journal-title":"Blood"},{"issue":"06","key":"ref51","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1055\/s-0038-1642511","article-title":"Factor VII and fibrinogen levels as risk factors for venous thrombosis. A case-control study of plasma levels and DNA polymorphisms \u2013 the Leiden Thrombophilia Study (LETS)","volume":"71","author":"T Koster","year":"1994","journal-title":"Thromb Haemost"},{"issue":"05","key":"ref52","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1055\/s-0037-1614553","article-title":"Increased levels of factor VIII and fibrinogen in patients with venous thrombosis are not caused by acute phase reactions","volume":"81","author":"P W Kamphuisen","year":"1999","journal-title":"Thromb Haemost"},{"issue":"12","key":"ref53","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1111\/j.1538-7836.2003.0543b.x","article-title":"High levels of fibrinogen are associated with the risk of deep venous thrombosis mainly in the elderly","volume":"1","author":"A van Hylckama Vlieg","year":"2003","journal-title":"J Thromb Haemost"},{"issue":"11","key":"ref54","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1111\/j.1538-7836.2005.01624.x","article-title":"A novel polymorphism in the factor XIII B-subunit (His95Arg): relationship to subunit dissociation and venous thrombosis","volume":"3","author":"N Komanasin","year":"2005","journal-title":"J Thromb Haemost"},{"issue":"05","key":"ref55","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1055\/s-0037-1614552","article-title":"Factor XIII Val34Leu is a genetic factor involved in the etiology of venous thrombosis","volume":"81","author":"R F Franco","year":"1999","journal-title":"Thromb Haemost"},{"issue":"07","key":"ref56","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1097\/01.mbc.0000245295.79891.86","article-title":"The factor XIII Val34Leu polymorphism: is it protective against idiopathic venous thromboembolism?","volume":"17","author":"P S Wells","year":"2006","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"02","key":"ref57","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/aje\/kwj179","article-title":"Factor XIII Val34Leu variant is protective against venous thromboembolism: a HuGE review and meta-analysis","volume":"164","author":"P S Wells","year":"2006","journal-title":"Am J Epidemiol"},{"issue":"08","key":"ref58","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1055\/s-0034-1395153","article-title":"Tissue factor pathway inhibitor: then and now","volume":"40","author":"P ER Ellery","year":"2014","journal-title":"Semin Thromb Hemost"},{"issue":"11","key":"ref59","doi-asserted-by":"crossref","first-page":"4387","DOI":"10.1182\/blood-2002-10-3188","article-title":"Low levels of tissue factor pathway inhibitor (TFPI) increase the risk of venous thrombosis","volume":"101","author":"A Dahm","year":"2003","journal-title":"Blood"},{"issue":"02","key":"ref60","first-page":"207","article-title":"Total tissue factor pathway inhibitor and venous thrombosis. The Longitudinal Investigation of Thromboembolism Etiology","volume":"104","author":"N A Zakai","year":"2010","journal-title":"Thromb Haemost"},{"issue":"04","key":"ref61","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1160\/TH05-06-0412","article-title":"Tissue factor pathway inhibitor and the risk of recurrent venous thromboembolism","volume":"94","author":"M Hoke","year":"2005","journal-title":"Thromb Haemost"},{"issue":"12","key":"ref62","doi-asserted-by":"crossref","first-page":"e14978","DOI":"10.1097\/MD.0000000000014978","article-title":"Association of TFPI polymorphisms rs8176592, rs10931292, and rs10153820 with venous thrombosis: a meta-analysis","volume":"98","author":"Y Zhang","year":"2019","journal-title":"Medicine (Baltimore)"},{"issue":"12","key":"ref63","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1182\/bloodadvances.2019001155","article-title":"A case of thrombomodulin mutation causing defective thrombin binding with absence of protein C and TAFI activation","volume":"4","author":"M Okada","year":"2020","journal-title":"Blood Adv"},{"issue":"04","key":"ref64","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1056\/NEJMoa0810739","article-title":"Thrombomodulin mutations in atypical hemolytic-uremic syndrome","volume":"361","author":"M Delvaeye","year":"2009","journal-title":"N Engl J Med"},{"issue":"01","key":"ref65","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1055\/s-0038-1657559","article-title":"Thrombomodulin gene variations and thromboembolic disease","volume":"78","author":"A K Ohlin","year":"1997","journal-title":"Thromb Haemost"},{"issue":"01","key":"ref66","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1161\/01.CIR.96.1.15","article-title":"Thrombomodulin gene mutations associated with myocardial infarction","volume":"96","author":"H Ireland","year":"1997","journal-title":"Circulation"},{"issue":"05","key":"ref67","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1055\/s-0037-1615352","article-title":"A mutation in the thrombomodulin gene, 127G to A coding for Ala25Thr, and the risk of myocardial infarction in men","volume":"80","author":"C J Doggen","year":"1998","journal-title":"Thromb Haemost"},{"issue":"02","key":"ref68","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1055\/s-0038-1655947","article-title":"A common thrombomodulin amino acid dimorphism is associated with myocardial infarction","volume":"77","author":"L Norlund","year":"1997","journal-title":"Thromb Haemost"},{"issue":"04","key":"ref69","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1161\/01.ATV.19.4.1098","article-title":"Mutations in promoter region of thrombomodulin and venous thromboembolic disease","volume":"19","author":"L Le Flem","year":"1999","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"04","key":"ref70","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1111\/j.1538-7836.2005.01187.x","article-title":"Thrombomodulin gene polymorphisms or haplotypes as potential risk factors for venous thromboembolism: a population-based case-control study","volume":"3","author":"J A Heit","year":"2005","journal-title":"J Thromb Haemost"},{"issue":"06","key":"ref71","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1161\/ATVBAHA.113.301360","article-title":"Association of the thrombomodulin gene c.1418C>T polymorphism with thrombomodulin levels and with venous thrombosis risk","volume":"33","author":"S Navarro","year":"2013","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"05","key":"ref72","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1055\/s-0038-1648181","article-title":"A frequent thrombomodulin amino acid dimorphism is not associated with thrombophilia","volume":"65","author":"P A van der Velden","year":"1991","journal-title":"Thromb Haemost"},{"issue":"01","key":"ref73","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1046\/j.1538-7836.2003.00029.x","article-title":"Prospective study of the A455V polymorphism in the thrombomodulin gene, plasma thrombomodulin, and incidence of venous thromboembolism: the LITE Study","volume":"1","author":"N Aleksic","year":"2003","journal-title":"J Thromb Haemost"},{"issue":"01","key":"ref74","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s11239-015-1328-x","article-title":"Thrombomodulin gene c.1418C>T polymorphism and risk of recurrent venous thromboembolism","volume":"42","author":"A Ahmad","year":"2016","journal-title":"J Thromb Thrombolysis"},{"issue":"19","key":"ref75","doi-asserted-by":"crossref","first-page":"10212","DOI":"10.1073\/pnas.93.19.10212","article-title":"The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex","volume":"93","author":"D J Stearns-Kurosawa","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"02","key":"ref76","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1172\/JCI119548","article-title":"Identification of functional endothelial protein C receptor in human plasma","volume":"100","author":"S Kurosawa","year":"1997","journal-title":"J Clin Invest"},{"issue":"08","key":"ref77","doi-asserted-by":"crossref","first-page":"5447","DOI":"10.1074\/jbc.275.8.5447","article-title":"Mechanisms by which soluble endothelial cell protein C receptor modulates protein C and activated protein C function","volume":"275","author":"P C Liaw","year":"2000","journal-title":"J Biol Chem"},{"issue":"04","key":"ref78","first-page":"945","article-title":"A 23bp insertion in the endothelial protein C receptor (EPCR) gene impairs EPCR function","volume":"86","author":"E Biguzzi","year":"2001","journal-title":"Thromb Haemost"},{"issue":"06","key":"ref79","first-page":"1360","article-title":"Prevalence of a 23bp insertion in exon 3 of the endothelial cell protein C receptor gene in venous thrombophilia","volume":"86","author":"M von Depka","year":"2001","journal-title":"Thromb Haemost"},{"issue":"04","key":"ref80","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1055\/s-0037-1615668","article-title":"The endothelial protein C receptor (EPCR) 23bp insert in patients with myocardial infarction","volume":"85","author":"N S Van de Water","year":"2001","journal-title":"Thromb Haemost"},{"issue":"03","key":"ref81","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/ajh.20519","article-title":"23-bp endothelial protein C receptor (EPCR) gene insertion mutation in cancer patients with and without thrombosis","volume":"81","author":"A Ero\u011dlu","year":"2006","journal-title":"Am J Hematol"},{"issue":"03","key":"ref82","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1161\/ATVBAHA.113.302518","article-title":"Functional analysis of two haplotypes of the human endothelial protein C receptor gene","volume":"34","author":"P Medina","year":"2014","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"08","key":"ref83","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1046\/j.1538-7836.2004.00855.x","article-title":"Haplotypes of the EPCR gene, plasma sEPCR levels and the risk of deep venous thrombosis","volume":"2","author":"S Uitte de Willige","year":"2004","journal-title":"J Thromb Haemost"},{"issue":"10","key":"ref84","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1182\/blood-2011-10-383448","article-title":"The endothelial protein C receptor (PROCR) Ser219Gly variant and risk of common thrombotic disorders: a HuGE review and meta-analysis of evidence from observational studies","volume":"119","author":"J Dennis","year":"2012","journal-title":"Blood"},{"issue":"02","key":"ref85","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1177\/1076029614547261","article-title":"Endothelial protein C receptor gene variants and risk of thrombosis","volume":"22","author":"G Anastasiou","year":"2016","journal-title":"Clin Appl Thromb Hemost"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.thromres.2018.07.006","article-title":"The H1 haplotype of the endothelial protein C receptor protects against arterial thrombosis in patients with antiphospholipid syndrome","volume":"169","author":"M A Plas\u00edn-Rodr\u00edguez","year":"2018","journal-title":"Thromb Res"},{"issue":"01","key":"ref87","first-page":"8","article-title":"Protein Z-dependent regulation of coagulation","volume":"86","author":"G J Broze Jr","year":"2001","journal-title":"Thromb Haemost"},{"issue":"19","key":"ref88","doi-asserted-by":"crossref","first-page":"7644","DOI":"10.1074\/jbc.RA118.006787","article-title":"Protein Z-dependent protease inhibitor (ZPI) is a physiologically significant inhibitor of prothrombinase function","volume":"294","author":"X Huang","year":"2019","journal-title":"J Biol Chem"},{"issue":"06","key":"ref89","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.thromres.2011.08.007","article-title":"The risk of occurrence of venous thrombosis: focus on protein Z","volume":"128","author":"V Bafunno","year":"2011","journal-title":"Thromb Res"},{"issue":"02","key":"ref90","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/j.1365-2141.2004.05189.x","article-title":"Mutations within the protein Z-dependent protease inhibitor gene are associated with venous thromboembolic disease: a new form of thrombophilia","volume":"127","author":"N Van de Water","year":"2004","journal-title":"Br J Haematol"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/S0140-6736(00)04218-5","article-title":"Frequency of protein Z deficiency in patients with ischaemic stroke","volume":"357","author":"M Vasse","year":"2001","journal-title":"Lancet"},{"issue":"03","key":"ref92","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1160\/TH04-11-0715","article-title":"Protein Z and protein Z-dependent protease inhibitor. Determinants of levels and risk of venous thrombosis","volume":"93","author":"A Al-Shanqeeti","year":"2005","journal-title":"Thromb Haemost"},{"issue":"04","key":"ref93","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1160\/TH09-09-0645","article-title":"A meta-analysis of potential risks of low levels of protein Z for diseases related to vascular thrombosis","volume":"103","author":"F Sofi","year":"2010","journal-title":"Thromb Haemost"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0049-3848(02)00181-0","article-title":"Protein Z influences the prothrombotic phenotype in factor V Leiden patients","volume":"106","author":"B Kemkes-Matthes","year":"2002","journal-title":"Thromb Res"},{"issue":"12","key":"ref95","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1111\/j.1538-7836.2005.01664.x","article-title":"Low levels of protein Z and the risk of venous thromboembolism","volume":"3","author":"I Martinelli","year":"2005","journal-title":"J Thromb Haemost"},{"issue":"01","key":"ref96","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1182\/blood-2005-08-3249","article-title":"A nonsense polymorphism in the protein Z-dependent protease inhibitor increases the risk for venous thrombosis","volume":"108","author":"J Corral","year":"2006","journal-title":"Blood"},{"issue":"02","key":"ref97","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/j.1365-2141.2008.07331.x","article-title":"Polymorphisms of the Z protein protease inhibitor and risk of venous thromboembolism: a meta-analysis","volume":"143","author":"F Dentali","year":"2008","journal-title":"Br J Haematol"},{"issue":"05","key":"ref98","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1160\/TH11-10-0708","article-title":"Two missense mutations identified in venous thrombosis patients impair the inhibitory function of the protein Z dependent protease inhibitor","volume":"107","author":"L K Young","year":"2012","journal-title":"Thromb Haemost"},{"issue":"03","key":"ref99","doi-asserted-by":"crossref","first-page":"e0151347","DOI":"10.1371\/journal.pone.0151347","article-title":"Single nucleotide variant rs2232710 in the protein Z-dependent protease inhibitor (ZPI, SERPINA10) gene is not associated with deep vein thrombosis","volume":"11","author":"M M Gorski","year":"2016","journal-title":"PLoS One"},{"issue":"02","key":"ref100","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/0003-9861(74)90354-3","article-title":"Identification of two distinct heparin cofactors in human plasma. Separation and partial purification","volume":"161","author":"G F Briginshaw","year":"1974","journal-title":"Arch Biochem Biophys"},{"issue":"01","key":"ref101","first-page":"109","article-title":"Prevalence of heparin cofactor II deficiency in patients with a history of venous thrombosis","volume":"48","author":"S Lopaciuk","year":"1996","journal-title":"Pol J Pharmacol"},{"issue":"01","key":"ref102","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.1365-2141.1991.tb07961.x","article-title":"Recurrent venous thrombosis associated with inherited deficiency of heparin cofactor II","volume":"77","author":"D J Weisdorf","year":"1991","journal-title":"Br J Haematol"},{"issue":"02","key":"ref103","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1055\/s-0038-1651093","article-title":"Hereditary heparin cofactor II deficiency and the risk of development of thrombosis","volume":"57","author":"R M Bertina","year":"1987","journal-title":"Thromb Haemost"},{"issue":"03","key":"ref104","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1055\/s-0037-1614320","article-title":"Hereditary homozygous heparin cofactor II deficiency and the risk of developing venous thrombosis","volume":"82","author":"P Villa","year":"1999","journal-title":"Thromb Haemost"},{"issue":"11","key":"ref105","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.5858\/2002-126-1394-HCID","article-title":"Heparin cofactor II deficiency","volume":"126","author":"D M Tollefsen","year":"2002","journal-title":"Arch Pathol Lab Med"},{"issue":"10","key":"ref106","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1161\/01.CIR.0000140763.51679.D9","article-title":"Homozygous deficiency of heparin cofactor II: relevance of P17 glutamate residue in serpins, relationship with conformational diseases, and role in thrombosis","volume":"110","author":"J Corral","year":"2004","journal-title":"Circulation"},{"issue":"04","key":"ref107","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S1357-2725(99)00138-7","article-title":"Homocysteine","volume":"32","author":"J D Finkelstein","year":"2000","journal-title":"Int J Biochem Cell Biol"},{"key":"ref108","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/S0140-6736(11)60872-6","article-title":"Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials","volume":"378","author":"M V Holmes","year":"2011","journal-title":"Lancet"},{"issue":"02","key":"ref109","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/j.1538-7836.2005.01141.x","article-title":"Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies","volume":"3","author":"M Den Heijer","year":"2005","journal-title":"J Thromb Haemost"},{"issue":"07","key":"ref110","first-page":"40","article-title":"Meta-analysis of the relationship between methylenetetrahydrofolate reductase C677T and A1298C polymorphism and venous thromboembolism in the Caucasian and Asian","volume":"40","author":"M Gao","year":"2020","journal-title":"Biosci Rep"},{"issue":"20","key":"ref111","doi-asserted-by":"crossref","first-page":"8613","DOI":"10.1007\/s00253-018-9266-0","article-title":"Formation of folates by microorganisms: towards the biotechnological production of this vitamin","volume":"102","author":"J L Revuelta","year":"2018","journal-title":"Appl Microbiol Biotechnol"},{"issue":"01","key":"ref112","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1182\/blood.V90.1.1","article-title":"Homocysteine and thrombotic disease","volume":"90","author":"A D'Angelo","year":"1997","journal-title":"Blood"},{"issue":"19","key":"ref113","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1001\/archinte.158.19.2101","article-title":"Meta-analysis of hyperhomocysteinemia as a risk factor for venous thromboembolic disease","volume":"158","author":"J G Ray","year":"1998","journal-title":"Arch Intern Med"},{"issue":"07","key":"ref114","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1001\/archinte.160.7.961","article-title":"Hyperhomocyst(e)inemia and the increased risk of venous thromboembolism: more evidence from a case-control study","volume":"160","author":"L J Langman","year":"2000","journal-title":"Arch Intern Med"},{"issue":"04","key":"ref115","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0049-3848(00)00324-8","article-title":"Mild hyperhomocysteinemia and fibrinolytic factors in patients with history of venous thromboembolism","volume":"100","author":"M Bo\u017ei\u010d","year":"2000","journal-title":"Thromb Res"},{"issue":"02","key":"ref116","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1160\/TH03-02-0038","article-title":"Increased fasting total homocysteine plasma levels as a risk factor for thromboembolism in children","volume":"91","author":"A Kosch","year":"2004","journal-title":"Thromb Haemost"},{"issue":"04","key":"ref117","first-page":"CD006612","article-title":"Homocysteine lowering interventions for preventing cardiovascular events","author":"A J Mart\u00ed-Carvajal","year":"2009","journal-title":"Cochrane Database Syst Rev"},{"issue":"02","key":"ref118","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1097\/01.mnh.0000441047.13912.56","article-title":"Renal angiotensin-converting enzyme and blood pressure control","volume":"23","author":"K E Bernstein","year":"2014","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"ref119","first-page":"419","article-title":"Prothrombotic effects of angiotensin","volume":"45","author":"N J Brown","year":"2000","journal-title":"Adv Intern Med"},{"issue":"04","key":"ref120","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1172\/JCI114844","article-title":"An insertion\/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels","volume":"86","author":"B Rigat","year":"1990","journal-title":"J Clin Invest"},{"issue":"01","key":"ref121","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1177\/1076029609349499","article-title":"Meta-analysis of association between insertion\/deletion polymorphism of the angiotensin I-converting enzyme gene and venous thromboembolism","volume":"17","author":"F-C Hsiao","year":"2011","journal-title":"Clin Appl Thromb Hemost"},{"issue":"01","key":"ref122","doi-asserted-by":"crossref","first-page":"e87813","DOI":"10.1371\/journal.pone.0087813","article-title":"Inhibition of renin angiotensin axis may be associated with reduced risk of developing venous thromboembolism in patients with atherosclerotic disease","volume":"9","author":"Y K Chae","year":"2014","journal-title":"PLoS One"},{"issue":"05","key":"ref123","doi-asserted-by":"crossref","first-page":"611","DOI":"10.5603\/CJ.a2017.0112","article-title":"Renin-angiotensin system inhibition is associated with reduced risk of left atrial appendage thrombosis formation in patients with atrial fibrillation","volume":"25","author":"Y Suo","year":"2018","journal-title":"Cardiol J"},{"key":"ref124","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1126\/science.3283935","article-title":"Apolipoprotein E: cholesterol transport protein with expanding role in cell biology","volume":"240","author":"R W Mahley","year":"1988","journal-title":"Science"},{"issue":"01","key":"ref125","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1161\/01.ATV.17.1.91","article-title":"Polymorphism of the apolipoprotein E gene and early carotid atherosclerosis defined by ultrasonography in asymptomatic adults","volume":"17","author":"L Cattin","year":"1997","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"06","key":"ref126","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1093\/aje\/155.6.487","article-title":"Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review","volume":"155","author":"J E Eichner","year":"2002","journal-title":"Am J Epidemiol"},{"key":"ref127","first-page":"1407183","article-title":"Apolipoprotein E \u03b54 polymorphism as a risk factor for ischemic stroke: a systematic review and meta-analysis","volume":"2022","author":"S Y Qiao","year":"2022","journal-title":"Dis Markers"},{"issue":"01","key":"ref128","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1007\/s11239-011-0639-9","article-title":"Association of ApoE genetic polymorphisms with proximal deep venous thrombosis","volume":"33","author":"L C Nagato","year":"2012","journal-title":"J Thromb Thrombolysis"},{"issue":"02","key":"ref129","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1177\/1076029609348646","article-title":"Association between ApoE4 allele and deep venous thrombosis: a pilot study","volume":"17","author":"N Katrancioglu","year":"2011","journal-title":"Clin Appl Thromb Hemost"},{"key":"ref130","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1476-511X-13-21","article-title":"Apolipoprotein E polymorphism is associated with lower extremity deep venous thrombosis: color-flow Doppler ultrasound evaluation","volume":"13","author":"S Zhu","year":"2014","journal-title":"Lipids Health Dis"},{"issue":"05","key":"ref131","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1177\/0268355518802693","article-title":"Thrombophilic risk factors are laterally associated with apolipoprotein E gene polymorphisms in deep vein thrombosis patients: an Indian study","volume":"34","author":"P Rastogi","year":"2019","journal-title":"Phlebology"},{"issue":"01","key":"ref132","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/jth.13898","article-title":"ADAMTS-13 and von Willebrand factor: a dynamic duo","volume":"16","author":"K South","year":"2018","journal-title":"J Thromb Haemost"},{"issue":"21","key":"ref133","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1182\/blood-2016-10-709857","article-title":"Thrombotic thrombocytopenic purpura","volume":"129","author":"B S Joly","year":"2017","journal-title":"Blood"},{"issue":"05","key":"ref134","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1177\/1076029610375815","article-title":"Polymorphisms and mutations in vWF and ADAMTS13 genes and their correlation with plasma levels of FVIII and vWF in patients with deep venous thrombosis","volume":"17","author":"L F Bittar","year":"2011","journal-title":"Clin Appl Thromb Hemost"},{"key":"ref135","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.thromres.2020.10.037","article-title":"ADAMTS13 activity, high VWF and FVIII levels in the pathogenesis of deep vein thrombosis","volume":"197","author":"M T Pagliari","year":"2021","journal-title":"Thromb Res"},{"issue":"07","key":"ref136","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1111\/jth.12291","article-title":"Next-generation sequencing study finds an excess of rare, coding single-nucleotide variants of ADAMTS13 in patients with deep vein thrombosis","volume":"11","author":"L A Lotta","year":"2013","journal-title":"J Thromb Haemost"},{"issue":"10","key":"ref137","doi-asserted-by":"crossref","first-page":"e0258675","DOI":"10.1371\/journal.pone.0258675","article-title":"Role of ADAMTS13, VWF and F8 genes in deep vein thrombosis","volume":"16","author":"M T Pagliari","year":"2021","journal-title":"PLoS 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