• 1
    Mackman N. Triggers, targets and treatments for thrombosis. Nature 2008; 451: 9148.
  • 2
    Rosendaal FR. Thrombosis in the young: epidemiology and risk factors. A focus on venous thrombosis. Thromb Haemost 1997; 78: 16.
  • 3
    Oger E. Incidence of venous thromboembolism: a community-based study in Western France. EPI-GETBP Study Group. Groupe d'Etude de la Thrombose de Bretagne Occidentale. Thromb Haemost 2000; 83: 65760.
  • 4
    Heit JA. The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol 2008; 28: 3702.
  • 5
    Larsen TB, Sorensen HT, Skytthe A, Johnsen SP, Vaupel JW, Christensen K. Major genetic susceptibility for venous thromboembolism in men: a study of Danish twins. Epidemiology 2003; 14: 32832.
  • 6
    Souto JC, Almasy L, Borrell M, Gari M, Martinez E, Mateo J, Stone WH, Blangero J, Fontcuberta J. Genetic determinants of hemostasis phenotypes in Spanish families. Circulation 2000; 101: 154651.
  • 7
    Zoller B, Li X, Sundquist J, Sundquist K. Age- and gender-specific familial risks for venous thromboembolism: a nationwide epidemiological study based on hospitalizations in Sweden. Circulation 2012; 124: 101220.
  • 8
    Germain M, Saut N, Greliche N, Dina C, Lambert JC, Perret C, Cohen W, Oudot-Mellakh T, Antoni G, Alessi MC, Zelenika D, Cambien F, Tiret L, Bertrand M, Dupuy AM, Letenneur L, Lathrop M, Emmerich J, Amouyel P, Tregouet DA, et al. Genetics of venous thrombosis: insights from a new genome wide association study. PLoS ONE 2011; 6: e25581.
  • 9
    Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thromb Diath Haemorrh 1965; 13: 51630.
  • 10
    Rau JC, Beaulieu LM, Huntington JA, Church FC. Serpins in thrombosis, hemostasis and fibrinolysis. J Thromb Haemost 2007; 5(Suppl. 1): 10215.
  • 11
    Seligsohn U, Lubetsky A. Genetic susceptibility to venous thrombosis. N Engl J Med 2001; 344: 122231.
  • 12
    Bucciarelli P, Passamonti SM, Biguzzi E, Gianniello F, Franchi F, Mannucci PM, Martinelli I. Low borderline plasma levels of antithrombin, protein C and protein S are risk factors for venous thromboembolism. J Thromb Haemost 2012; 10: 178391.
  • 13
    Anton AI, Teruel R, Corral J, Minano A, Martinez-Martinez I, Ordonez A, Vicente V, Sanchez-Vega B. Functional consequences of the prothrombotic SERPINC1 rs2227589 polymorphism on antithrombin levels. Haematologica 2009; 94: 58992.
  • 14
    Bezemer ID, Bare LA, Doggen CJ, Arellano AR, Tong C, Rowland CM, Catanese J, Young BA, Reitsma PH, Devlin JJ, Rosendaal FR. Gene variants associated with deep vein thrombosis. JAMA 2008; 299: 130614.
  • 15
    Oudot-Mellakh T, Cohen W, Germain M, Saut N, Kallel C, Zelenika D, Lathrop M, Tregouet DA, Morange PE. Genome wide association study for plasma levels of natural anticoagulant inhibitors and protein C anticoagulant pathway: the MARTHA project. Br J Haematol 2012; 157: 2309.
  • 16
    Jick H, Slone D, Westerholm B, Inman WH, Vessey MP, Shapiro S, Lewis GP, Worcester J. Venous thromboembolic disease and ABO blood type. A cooperative study. Lancet 1969; 1: 53942.
  • 17
    Wu O, Bayoumi N, Vickers MA, Clark P. ABO(H) blood groups and vascular disease: a systematic review and meta-analysis. J Thromb Haemost 2008; 6: 629.
  • 18
    Tregouet DA, Heath S, Saut N, Biron-Andreani C, Schved JF, Pernod G, Galan P, Drouet L, Zelenika D, Juhan-Vague I, Alessi MC, Tiret L, Lathrop M, Emmerich J, Morange PE. Common susceptibility alleles are unlikely to contribute as strongly as the FV and ABO loci to VTE risk: results from a GWAS approach. Blood 2009; 113: 5298303.
  • 19
    Heit JA, Armasu SM, Asmann YW, Cunningham JM, Matsumoto ME, Petterson TM, De Andrade M. A genome-wide association study of venous thromboembolism identifies risk variants in chromosomes 1q24.2 and 9q. J Thromb Haemost 2012; 10: 152131.
  • 20
    Yamamoto F, McNeill PD, Hakomori S. Human histo-blood group A2 transferase coded by A2 allele, one of the A subtypes, is characterized by a single base deletion in the coding sequence, which results in an additional domain at the carboxyl terminal. Biochem Biophys Res Commun 1992; 187: 36674.
  • 21
    Heit JA, Cunningham JM, Petterson TM, Armasu SM, Rider DN, De Andrade M. Genetic variation within the anticoagulant, procoagulant, fibrinolytic and innate immunity pathways as risk factors for venous thromboembolism. J Thromb Haemost 2011; 9: 113342.
  • 22
    Jenkins PV, O'Donnell JS. ABO blood group determines plasma von Willebrand factor levels: a biologic function after all? Transfusion 2006; 46: 183644.
  • 23
    McGrath RT, McKinnon TA, Byrne B, O'Kennedy R, Terraube V, McRae E, Preston RJ, Laffan MA, O'Donnell JS. Expression of terminal alpha2-6-linked sialic acid on von Willebrand factor specifically enhances proteolysis by ADAMTS13. Blood 2010; 115: 266673.
  • 24
    Ohira T, Cushman M, Tsai MY, Zhang Y, Heckbert SR, Zakai NA, Rosamond WD, Folsom AR. ABO blood group, other risk factors and incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE). J Thromb Haemost 2007; 5: 145561.
  • 25
    Cohen W, Castelli C, Alessi MC, Aillaud MF, Bouvet S, Saut N, Brunet D, Barthet MC, Tregouet DA, Lavigne G, Morange PE. ABO blood group and von Willebrand factor levels partially explained the incomplete penetrance of congenital thrombophilia. Arterioscler Thromb Vasc Biol 2012; 32: 20218.
  • 26
    Kiechl S, Pare G, Barbalic M, Qi L, Dupuis J, Dehghan A, Bis JC, Laxton RC, Xiao Q, Bonora E, Willeit J, Xu Q, Witteman JC, Chasman D, Tracy RP, Ballantyne CM, Ridker PM, Benjamin EJ, Ye S. Association of Variation at the ABO Locus with Circulating Levels of sICAM-1, sP-selectin and sE-selectin: a meta-analysis. Circ Cardiovasc Genet 2011; 4: 6816.
  • 27
    Schunkert H, Konig IR, Kathiresan S, Reilly MP, Assimes TL, Holm H, Preuss M, Stewart AF, Barbalic M, Gieger C, Absher D, Aherrahrou Z, Allayee H, Altshuler D, Anand SS, Andersen K, Anderson JL, Ardissino D, Ball SG, Balmforth AJ, et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet 2011; 43: 3338.
  • 28
    Amundadottir L, Kraft P, Stolzenberg-Solomon RZ, Fuchs CS, Petersen GM, Arslan AA, Bueno-de-Mesquita HB, Gross M, Helzlsouer K, Jacobs EJ, LaCroix A, Zheng W, Albanes D, Bamlet W, Berg CD, Berrino F, Bingham S, Buring JE, Bracci PM, Canzian F, et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet 2009; 41: 98690.
  • 29
    Koster T, Blann AD, Briet E, Vandenbroucke JP, Rosendaal FR. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep vein thrombosis. Lancet 1995; 345: 1525.
  • 30
    Smith NL, Rice KM, Bovill EG, Cushman M, Bis JC, McKnight B, Lumley T, Glazer NL, van Hylckama Vlieg A, Tang W, Dehghan A, Strachan DP, O'Donnell CJ, Rotter JI, Heckbert SR, Psaty BM, Rosendaal FR. Genetic variation associated with plasma von Willebrand factor levels and the risk of incident venous thrombosis. Blood 2011; 117: 600711.
  • 31
    Smith NL, Chen MH, Dehghan A, Strachan DP, Basu S, Soranzo N, Hayward C, Rudan I, Sabater-Lleal M, Bis JC, de Maat MP, Rumley A, Kong X, Yang Q, Williams FM, Vitart V, Campbell H, Malarstig A, Wiggins KL, van Duijn CM, et al. Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium. Circulation 2010; 121: 138292.
  • 32
    Antoni G, Morange PE, Luo Y, Saut N, Burgos G, Heath S, Germain M, Biron-Andreani C, Schved JF, Pernod G, Galan P, Zelenika D, Alessi MC, Drouet L, Visvikis-Siest S, Wells PS, Lathrop M, Emmerich J, Tregouet DA, Gagnon F. A multi-stage multi-design strategy provides strong evidence that the BAI3 locus is associated with early-onset venous thromboembolism. J Thromb Haemost 2010; 8: 26719.
  • 33
    Morange PE, Saut N, Antoni G, Emmerich J, Tregouet DA. Impact on venous thrombosis risk of newly discovered gene variants associated with FVIII and VWF plasma levels. J Thromb Haemost 2011; 9: 22931.
  • 34
    van Loon JE, Sanders YV, de Wee EM, Kruip MJ, de Maat MP, Leebeek FW. Effect of genetic variation in STXBP5 and STX2 on von Willebrand factor and bleeding phenotype in type 1 von Willebrand disease patients. PLoS ONE 2012; 7: e40624.
  • 35
    van Loon JE, Leebeek FW, Deckers JW, Dippel DW, Poldermans D, Strachan DP, Tang W, O'Donnell CJ, Smith NL, de Maat MP. Effect of genetic variations in syntaxin-binding protein-5 and syntaxin-2 on von Willebrand factor concentration and cardiovascular risk. Circ Cardiovasc Genet 2012; 3: 50712.
  • 36
    Lowenstein CJ, Morrell CN, Yamakuchi M. Regulation of Weibel-Palade body exocytosis. Trends Cardiovasc Med 2005; 15: 3028.
  • 37
    Widberg CH, Bryant NJ, Girotti M, Rea S, James DE. Tomosyn interacts with the t-SNAREs syntaxin4 and SNAP23 and plays a role in insulin-stimulated GLUT4 translocation. J Biol Chem 2003; 278: 35093101.
  • 38
    Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Investig 1981; 68: 13703.
  • 39
    Dahlback B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood 2008; 112: 1927.
  • 40
    Folsom AR, Aleksic N, Wang L, Cushman M, Wu KK, White RH. Protein C, antithrombin, and venous thromboembolism incidence: a prospective population-based study. Arterioscler Thromb Vasc Biol 2002; 22: 101822.
  • 41
    Spek CA, Koster T, Rosendaal FR, Bertina RM, Reitsma PH. Genotypic variation in the promoter region of the protein C gene is associated with plasma protein C levels and thrombotic risk. Arterioscler Thromb Vasc Biol 1995; 15: 2148.
  • 42
    Aiach M, Nicaud V, Alhenc-Gelas M, Gandrille S, Arnaud E, Amiral J, Guize L, Fiessinger JN, Emmerich J. Complex association of protein C gene promoter polymorphism with circulating protein C levels and thrombotic risk. Arterioscler Thromb Vasc Biol 1999; 19: 15736.
  • 43
    Reiner AP, Carty CL, Jenny NS, Nievergelt C, Cushman M, Stearns-Kurosawa DJ, Kurosawa S, Kuller LH, Lange LA. PROC, PROCR and PROS1 polymorphisms, plasma anticoagulant phenotypes, and risk of cardiovascular disease and mortality in older adults: the Cardiovascular Health Study. J Thromb Haemost 2008; 6: 162532.
  • 44
    Tang W, Basu S, Kong X, Pankow JS, Aleksic N, Tan A, Cushman M, Boerwinkle E, Folsom AR. Genome-wide association study identifies novel loci for plasma levels of protein C: the ARIC study. Blood 2010; 116: 50326.
  • 45
    Stearns-Kurosawa DJ, Kurosawa S, Mollica JS, Ferrell GL, Esmon CT. The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc Natl Acad Sci USA 1996; 93: 102126.
  • 46
    Saposnik B, Reny JL, Gaussem P, Emmerich J, Aiach M, Gandrille S. A haplotype of the EPCR gene is associated with increased plasma levels of sEPCR and is a candidate risk factor for thrombosis. Blood 2004; 103: 13118.
  • 47
    Uitte de Willige S, van Marion V, Rosendaal FR, Vos HL, de Visser MC, Bertina RM. Haplotypes of the EPCR gene, plasma sEPCR levels and the risk of deep venous thrombosis. J Thromb Haemost 2004; 2: 130510.
  • 48
    Medina P, Navarro S, Estelles A, Vaya A, Woodhams B, Mira Y, Villa P, Migaud-Fressart M, Ferrando F, Aznar J, Bertina RM, Espana F. Contribution of polymorphisms in the endothelial protein C receptor gene to soluble endothelial protein C receptor and circulating activated protein C levels, and thrombotic risk. Thromb Haemost 2004; 91: 90511.
  • 49
    Ireland H, Konstantoulas CJ, Cooper JA, Hawe E, Humphries SE, Mather H, Goodall AH, Hogwood J, Juhan-Vague I, Yudkin JS, di Minno G, Margaglione M, Hamsten A, Miller GJ, Bauer KA, Kim YT, Stearns-Kurosawa DJ, Kurosawa S. EPCR Ser219Gly: elevated sEPCR, prothrombin F1 + 2, risk for coronary heart disease, and increased sEPCR shedding in vitro. Atherosclerosis 2005; 183: 28392.
  • 50
    Chinthammitr Y, Vos HL, Rosendaal FR, Doggen CJ. The association of prothrombin A19911G polymorphism with plasma prothrombin activity and venous thrombosis: results of the MEGA study, a large population-based case-control study. J Thromb Haemost 2006; 4: 258792.
  • 51
    Saposnik B, Lesteven E, Lokajczyk A, Esmon CT, Aiach M, Gandrille S. Alternative mRNA is favored by the A3 haplotype of the EPCR gene PROCR and generates a novel soluble form of EPCR in plasma. Blood 2008; 111: 344251.
  • 52
    Ireland HA, Cooper JA, Drenos F, Acharya J, Mitchell JP, Bauer KA, Morrissey JH, Esnouf MP, Humphries SE. FVII, FVIIa, and downstream markers of extrinsic pathway activation differ by EPCR Ser219Gly variant in healthy men. Arterioscler Thromb Vasc Biol 2009; 29: 196874.
  • 53
    Ghosh S, Pendurthi UR, Steinoe A, Esmon CT, Rao LV. Endothelial cell protein C receptor acts as a cellular receptor for factor VIIa on endothelium. J Biol Chem 2007; 282: 1184957.
  • 54
    Tang W, Schwienbacher C, Lopez LM, Ben-Shlomo Y, Oudot-Mellakh T, Johnson AD, Samani NJ, Basu S, Gogele M, Davies G, Lowe GD, Tregouet DA, Tan A, Pankow JS, Tenesa A, Levy D, Volpato CB, Rumley A, Gow AJ, Minelli C, et al. Genetic associations for activated partial thromboplastin time and prothrombin time, their gene expression profiles, and risk of coronary artery disease. Am J Hum Genet 2012; 91: 15262.
  • 55
    Dennis J, Johnson CY, Adediran AS, de Andrade M, Heit JA, Morange PE, Tregouet DA, Gagnon F. 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. Blood 2012; 119: 2392400.
  • 56
    Comp PC, Esmon CT. Recurrent venous thromboembolism in patients with a partial deficiency of protein S. N Engl J Med 1984; 311: 15258.
  • 57
    Beauchamp NJ, Dykes AC, Parikh N, Campbell Tait R, Daly ME. The prevalence of, and molecular defects underlying, inherited protein S deficiency in the general population. Br J Haematol 2004; 125: 64754.
  • 58
    Athanasiadis G, Buil A, Souto JC, Borrell M, Lopez S, Martinez-Perez A, Lathrop M, Fontcuberta J, Almasy L, Soria JM. A genome-wide association study of the Protein C anticoagulant pathway. PLoS ONE 2011; 6: e29168.
  • 59
    Buil A, Tregouet DA, Souto JC, Saut N, Germain M, Rotival M, Tiret L, Cambien F, Lathrop M, Zeller T, Alessi MC, Rodriguez de Cordoba S, Munzel T, Wild P, Fontcuberta J, Gagnon F, Emmerich J, Almasy L, Blankenberg S, Soria JM, Morange PE. C4BPB/C4BPA is a new susceptibility locus for venous thrombosis with unknown protein S-independent mechanism: results from genome-wide association and gene expression analyses followed by case-control studies. Blood 2010; 115: 464450.
  • 60
    van de Poel RH, Meijers JC, Rosing J, Tans G, Bouma BN. C4b-binding protein protects coagulation factor Va from inactivation by activated protein C. Biochemistry 2000; 39: 145438.
  • 61
    Esmon CT. Inflammation and thrombosis. J Thromb Haemost 2003; 1: 13438. 261 [pii].
  • 62
    Dahlback B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 10048.
  • 63
    Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 647.
  • 64
    Smith NL, Hindorff LA, Heckbert SR, Lemaitre RN, Marciante KD, Rice K, Lumley T, Bis JC, Wiggins KL, Rosendaal FR, Psaty BM. Association of genetic variations with nonfatal venous thrombosis in postmenopausal women. JAMA 2007; 297: 48998.
  • 65
    Bezemer ID, Bare LA, Arellano AR, Reitsma PH, Rosendaal FR. Updated analysis of gene variants associated with deep vein thrombosis. JAMA 2010; 303: 4212.
  • 66
    Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698703.
  • 67
    Castoldi E, Rosing J. APC resistance: biological basis and acquired influences. J Thromb Haemost 2010; 8: 44553.
  • 68
    Martinelli I, Battaglioli T, Tosetto A, Legnani C, Sottile L, Ghiotto R, Mannucci PM. Prothrombin A19911G polymorphism and the risk of venous thromboembolism. J Thromb Haemost 2006; 4: 25826.
  • 69
    von Ahsen N, Oellerich M. The intronic prothrombin 19911A>G polymorphism influences splicing efficiency and modulates effects of the 20210G>A polymorphism on mRNA amount and expression in a stable reporter gene assay system. Blood 2004; 103: 58693.
  • 70
    Weisel JW. Fibrinogen and fibrin. Adv Protein Chem 2005; 70: 24799.
  • 71
    Kant JA, Fornace AJ Jr, Saxe D, Simon MI, McBride OW, Crabtree GR. Evolution and organization of the fibrinogen locus on chromosome 4: gene duplication accompanied by transposition and inversion. Proc Natl Acad Sci USA 1985; 82: 23448.
  • 72
    Chung DW, Davie EW. gamma and gamma' chains of human fibrinogen are produced by alternative mRNA processing. Biochemistry 1984; 23: 42326.
  • 73
    Drouet L, Paolucci F, Pasqualini N, Laprade M, Ripoll L, Mazoyer E, Bal dit Sollier C, Vanhove N. Plasma gamma'/gamma fibrinogen ratio, a marker of arterial thrombotic activity: a new potential cardiovascular risk factor? Blood Coagul Fibrinolysis 1999; 10(Suppl. 1): S359.
  • 74
    Uitte de Willige S, de Visser MC, Houwing-Duistermaat JJ, Rosendaal FR, Vos HL, Bertina RM. Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen gamma' levels. Blood 2005; 106: 417683.
  • 75
    Lovely RS, Yang Q, Massaro JM, Wang J, D'Agostino RB Sr, O'Donnell CJ, Shannon J, Farrell DH. Assessment of genetic determinants of the association of gamma' fibrinogen in relation to cardiovascular disease. Arterioscler Thromb Vasc Biol 2012; 31: 234552.
  • 76
    Meijers JC, Tekelenburg WL, Bouma BN, Bertina RM, Rosendaal FR. High levels of coagulation factor XI as a risk factor for venous thrombosis. N Engl J Med 2000; 342: 696701.
  • 77
    Gailani D, Broze GJ Jr. Factor XI activation in a revised model of blood coagulation. Science 1991; 253: 90912.
  • 78
    Naito K, Fujikawa K. Activation of human blood coagulation factor XI independent of factor XII. Factor XI is activated by thrombin and factor XIa in the presence of negatively charged surfaces. J Biol Chem 1991; 266: 73538.
  • 79
    Austin H, De Staercke C, Lally C, Bezemer ID, Rosendaal FR, Craig Hooper W. New gene variants associated with venous thrombosis - a replication study in United States whites and blacks. J Thromb Haemost 2011; 9: 48995.
  • 80
    Snoep JD, Gaussem P, Eikenboom JC, Emmerich J, Zwaginga JJ, Holmes CE, Vos HL, de Groot PG, Herrington DM, Bray PF, Rosendaal FR, van der Bom JG. The minor allele of GP6 T13254C is associated with decreased platelet activation and a reduced risk of recurrent cardiovascular events and mortality: results from the SMILE-Platelets project. J Thromb Haemost 2010; 8: 237784.
  • 81
    Vanschoonbeek K, Feijge MA, van Kampen RJ, Kenis H, Hemker HC, Giesen PL, Heemskerk JW. Initiating and potentiating role of platelets in tissue factor-induced thrombin generation in the presence of plasma: subject-dependent variation in thrombogram characteristics. J Thromb Haemost 2004; 2: 47684.
  • 82
    Becattini C, Agnelli G, Schenone A, Eichinger S, Bucherini E, Silingardi M, Bianchi M, Moia M, Ageno W, Vandelli MR, Grandone E, Prandoni P. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med 2012; 366: 195967.
  • 83
    Brighton TA, Eikelboom JW, Mann K, Mister R, Gallus A, Ockelford P, Gibbs H, Hague W, Xavier D, Diaz R, Kirby A, Simes J. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med 2012; 367: 197987.
  • 84
    Morange PE, Bezemer I, Saut N, Bare L, Burgos G, Brocheton J, Durand H, Biron-Andreani C, Schved JF, Pernod G, Galan P, Drouet L, Zelenika D, Germain M, Nicaud V, Heath S, Ninio E, Delluc A, Munzel T, Zeller T, et al. A follow-up study of a genome-wide association scan identifies a susceptibility locus for venous thrombosis on chromosome 6p24.1. Am J Hum Genet 2010; 86: 5925.
  • 85
    Baldwin AS Jr, LeClair KP, Singh H, Sharp PA. A large protein containing zinc finger domains binds to related sequence elements in the enhancers of the class I major histocompatibility complex and kappa immunoglobulin genes. Mol Cell Biol 1990; 10: 140614.
  • 86
    Fan CM, Maniatis T. A DNA-binding protein containing two widely separated zinc finger motifs that recognize the same DNA sequence. Genes Dev 1990; 4: 2942.
  • 87
    Muchardt C, Seeler JS, Nirula A, Shurland DL, Gaynor RB. Regulation of human immunodeficiency virus enhancer function by PRDII-BF1 and c-rel gene products. J Virol 1992; 66: 24450.
  • 88
    Seeler JS, Muchardt C, Suessle A, Gaynor RB. Transcription factor PRDII-BF1 activates human immunodeficiency virus type 1 gene expression. J Virol 1994; 68: 10029.
  • 89
    Tripodi A, Chantarangkul V, Martinelli I, Bucciarelli P, Mannucci PM. A shortened activated partial thromboplastin time is associated with the risk of venous thromboembolism. Blood 2004; 104: 36314.
  • 90
    Houlihan LM, Davies G, Tenesa A, Harris SE, Luciano M, Gow AJ, McGhee KA, Liewald DC, Porteous DJ, Starr JM, Lowe GD, Visscher PM, Deary IJ. Common variants of large effect in F12, KNG1, and HRG are associated with activated partial thromboplastin time. Am J Hum Genet 2010; 86: 62631.
  • 91
    Morange PE, Oudot-Mellakh T, Cohen W, Germain M, Saut N, Antoni G, Alessi MC, Bertrand M, Dupuy AM, Letenneur L, Lathrop M, Lopez LM, Lambert JC, Emmerich J, Amouyel P, Tregouet DA. KNG1 Ile581Thr and susceptibility to venous thrombosis. Blood 2011; 117: 36924.
  • 92
    Gailani D, Renne T. The intrinsic pathway of coagulation: a target for treating thromboembolic disease? J Thromb Haemost 2007; 5: 110612.
  • 93
    Merkulov S, Zhang WM, Komar AA, Schmaier AH, Barnes E, Zhou Y, Lu X, Iwaki T, Castellino FJ, Luo G, McCrae KR. Deletion of murine kininogen gene 1 (mKng1) causes loss of plasma kininogen and delays thrombosis. Blood 2008; 111: 127481.
  • 94
    Cheng Q, Tucker EI, Pine MS, Sisler I, Matafonov A, Sun MF, White-Adams TC, Smith SA, Hanson SR, McCarty OJ, Renne T, Gruber A, Gailani D. A role for factor XIIa-mediated factor XI activation in thrombus formation in vivo. Blood 2010; 116: 39819.
  • 95
    Sabater-Lleal M, Martinez-Perez A, Buil A, Folkersen L, Souto JC, Bruzelius M, Borrell M, Odeberg J, Silveira A, Eriksson P, Almasy L, Hamsten A, Soria JM. A genome-wide association study identifies KNG1 as a genetic determinant of plasma factor XI Level and activated partial thromboplastin time. Arterioscler Thromb Vasc Biol 2012; 32: 200816.
  • 96
    Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, Thompson JR, Ingelsson E, Saleheen D, Erdmann J, Goldstein BA, Stirrups K, Konig IR, Cazier JB, Johansson A, Hall AS, Lee JY, Willer CJ, Chambers JC, Esko T, Folkersen L, et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet 2012; 45: 2533.
  • 97
    Nejentsev S, Walker N, Riches D, Egholm M, Todd JA. Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science 2009; 324: 3879.
  • 98
    Rivas MA, Beaudoin M, Gardet A, Stevens C, Sharma Y, Zhang CK, Boucher G, Ripke S, Ellinghaus D, Burtt N, Fennell T, Kirby A, Latiano A, Goyette P, Green T, Halfvarson J, Haritunians T, Korn JM, Kuruvilla F, Lagace C, et al. Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat Genet 2011; 43: 106673.
  • 99
    Simioni P, Tormene D, Tognin G, Gavasso S, Bulato C, Iacobelli NP, Finn JD, Spiezia L, Radu C, Arruda VR. X-linked thrombophilia with a mutant factor IX (factor IX Padua). N Engl J Med 2009; 361: 16715.
  • 100
    Miyawaki Y, Suzuki A, Fujita J, Maki A, Okuyama E, Murata M, Takagi A, Murate T, Kunishima S, Sakai M, Okamoto K, Matsushita T, Naoe T, Saito H, Kojima T. Thrombosis from a prothrombin mutation conveying antithrombin resistance. N Engl J Med 2012; 366: 23906.
  • 101
    Lotta LA, Wang M, Yu J, Martinelli I, Yu F, Passamonti SM, Consonni D, Pappalardo E, Menegatti M, Scherer SE, Lewis LL, Akbar H, Wu Y, Bainbridge MN, Muzny DM, Mannucci PM, Gibbs RA, Peyvandi F. Identification of genetic risk variants for deep vein thrombosis by multiplexed next-generation sequencing of 186 hemostatic/pro-inflammatory genes. BMC Med Genomics 2012; 5: 7.
  • 102
    Kim DS, Burt AA, Crosslin DR, Robertson PD, Ranchalis JE, Boyko EJ, Nickerson DA, Furlong CE, Jarvik GP. Novel common and rare genetic determinants of paraoxonase activity: FTO, SERPINA12, and ITGAL. J Lipid Res 2013; 54: 55260.
  • 103
    Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, Shaffer T, Wong M, Bhattacharjee A, Eichler EE, Bamshad M, Nickerson DA, Shendure J. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 2009; 461: 2726.
  • 104
    Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR, Zumbo P, Nayir A, Bakkaloglu A, Ozen S, Sanjad S, Nelson-Williams C, Farhi A, Mane S, Lifton RP. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci USA 2009; 106: 19096101.
  • 105
    Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet 2010; 42: 305.
  • 106
    White RH, Zhou H, Murin S, Harvey D. Effect of ethnicity and gender on the incidence of venous thromboembolism in a diverse population in California in 1996. Thromb Haemost 2005; 93: 298305.
  • 107
    White RH, Keenan CR. Effects of race and ethnicity on the incidence of venous thromboembolism. Thromb Res 2009; 123(Suppl. 4): S117.
  • 108
    Zakai NA, McClure LA. Racial differences in venous thromboembolism. J Thromb Haemost 2011; 9: 187782.
  • 109
    Buckner TW, Key NS. Venous thrombosis in blacks. Circulation 2012; 125: 8379.
  • 110
    Lutsey PL, Cushman M, Steffen LM, Green D, Barr RG, Herrington D, Ouyang P, Folsom AR. Plasma hemostatic factors and endothelial markers in four racial/ethnic groups: the MESA study. J Thromb Haemost 2006; 4: 262935.
  • 111
    Khaleghi M, Saleem U, McBane RD, Mosley TH Jr, Kullo IJ. African-American ethnicity is associated with higher plasma levels of D-dimer in adults with hypertension. J Thromb Haemost 2009; 7: 3440.
  • 112
    Greliche N, Germain M, Lambert JC, Cohen W, Bertrand M, Dupuis AM, Letenneur L, Lathrop M, Amouyel P, Morange PE, Tregouet DA. A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis. BMC Med Genet 2013; 14: 36.
  • 113
    Kearon C, Crowther M, Hirsh J. Management of patients with hereditary hypercoagulable disorders. Annu Rev Med 2000; 51: 16985.
  • 114
    van Cott EM, Laposata M, Prins MH. Laboratory evaluation of hypercoagulability with venous or arterial thrombosis. Arch Pathol Lab Med 2002; 126: 128195.
  • 115
    Crowther MA, Kelton JG. Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system. Ann Intern Med 2003; 138: 12834.
  • 116
    Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation 2003; 107: I916.
  • 117
    Carraro P. Guidelines for the laboratory investigation of inherited thrombophilias. Recommendations for the first level clinical laboratories. Clin Chem Lab Med 2003; 41: 38291.
  • 118
    Lussana F, Dentali F, Abbate R, d'Aloja E, D'Angelo A, De Stefano V, Faioni EM, Grandone E, Legnani C, Martinelli I, Simioni P, Tormene D. Screening for thrombophilia and antithrombotic prophylaxis in pregnancy: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET). Thromb Res 2009; 124: e1925.
  • 119
    Pernod G, Biron-Andreani C, Morange PE, Boehlen F, Constans J, Couturaud F, Drouet L, Jude B, Lecompte T, Le Gal G, Trillot N, Wahl D. Recommendations on testing for thrombophilia in venous thromboembolic disease: a French consensus guideline. J Mal Vasc 2009; 34: 156203.
  • 120
    Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D, Machin S, Mackie I, Makris M, Nokes T, Perry D, Tait RC, Walker I, Watson H. Clinical guidelines for testing for heritable thrombophilia. Br J Haematol 2010; 149: 20920.
  • 121
    Baglin T, Luddington R, Brown K, Baglin C. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet 2003; 362: 5236.
  • 122
    Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR. Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA 2005; 293: 235261.
  • 123
    Lussana F, Coppens M, Cattaneo M, Middeldorp S. Pregnancy-related venous thromboembolism: risk and the effect of thromboprophylaxis. Thromb Res 2012; 129: 67380.
  • 124
    Jacobsen AF, Sandset PM. Venous thromboembolism associated with pregnancy and hormonal therapy. Best Practice & Research 2012; 25: 31932.
  • 125
    Bezemer ID, van der Meer FJ, Eikenboom JC, Rosendaal FR, Doggen CJ. The value of family history as a risk indicator for venous thrombosis. Arch Intern Med 2009; 169: 6105.
  • 126
    van Hylckama Vlieg A, Baglin CA, Bare LA, Rosendaal FR, Baglin TP. Proof of principle of potential clinical utility of multiple SNP analysis for prediction of recurrent venous thrombosis. J Thromb Haemost 2008; 6: 7514.
  • 127
    de Haan HG, Bezemer ID, Doggen CJ, Le Cessie S, Reitsma PH, Arellano AR, Tong CH, Devlin JJ, Bare LA, Rosendaal FR, Vossen CY. Multiple SNP testing improves risk prediction of first venous thrombosis. Blood 2012; 120: 65663.
  • 128
    van Langevelde K, Flinterman LE, van Hylckama Vlieg A, Rosendaal FR, Cannegieter SC. Broadening the factor V Leiden paradox: pulmonary embolism and deep vein thrombosis as 2 sides of the spectrum. Blood 2012; 120: 93346.
  • 129
    Rosendaal FR. Once and only once. Circulation 2010; 121: 168890.