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Thromb Haemost 2020; 120(06): 883-993
DOI: 10.1055/s-0040-1710013
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Role of Factor XIa and Plasma Kallikrein in Arterial and Venous Thrombosis

Mayken Visser
1   Laboratory for Clinical Thrombosis and Haemostasis, Departments of Biochemistry and Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
2   Research & Development, Cardiovascular Research, Bayer AG, Wuppertal, Germany
,
Stefan Heitmeier
2   Research & Development, Cardiovascular Research, Bayer AG, Wuppertal, Germany
,
Hugo ten Cate
1   Laboratory for Clinical Thrombosis and Haemostasis, Departments of Biochemistry and Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
,
Henri M. H. Spronk
1   Laboratory for Clinical Thrombosis and Haemostasis, Departments of Biochemistry and Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
› Author Affiliations Funding None.
Further Information

Publication History

15 January 2020

17 March 2020

Publication Date:
06 May 2020 (online)

Also available at
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Abstract

Cardiovascular disease, including stroke, myocardial infarction, and venous thromboembolism, is one of the leading causes of morbidity and mortality worldwide. Excessive coagulation may cause vascular occlusion in arteries and veins eventually leading to thrombotic diseases. Studies in recent years suggest that coagulation factors are involved in these pathological mechanisms. Factors XIa (FXIa), XIIa (FXIIa), and plasma kallikrein (PKa) of the contact system of coagulation appear to contribute to thrombosis while playing a limited role in hemostasis. Contact activation is initiated upon autoactivation of FXII on negatively charged surfaces. FXIIa activates plasma prekallikrein (PK) to PKa, which in turn activates FXII and initiates the kallikrein–kinin pathway. FXI is also activated by FXIIa, leading to activation of FIX and finally to thrombin formation, which in turn activates FXI in an amplification loop. Animal studies have shown that arterial and venous thrombosis can be reduced by the inhibition of FXI(a) or PKa. Furthermore, data from human studies suggest that these enzymes may be valuable targets to reduce thrombosis risk. In this review, we discuss the structure and function of FXI(a) and PK(a), their involvement in the development of venous and arterial thrombosis in animal models and human studies, and current therapeutic strategies.

Keywords

factor XI - plasma kallikrein - thrombosis - animal models - clinical studies
 

  • References

  • 1 Roth GA, Johnson C, Abajobir A. , et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol 2017; 70 (01) 1-25
    CrossrefPubMedSearch in Google Scholar
  • 2 Furie B, Furie BC. Mechanisms of thrombus formation. N Engl J Med 2008; 359 (09) 938-949
    CrossrefPubMedSearch in Google Scholar
  • 3 MacFarlane RG. An enzyme cascade in the blood clotting mechanism, and its function as a biochemical amplifier. Nature 1964; 202: 498-499
    CrossrefPubMedSearch in Google Scholar
  • 4 Davie EW, Ratnoff OD. Waterfall sequence for intrinsic blood clotting. Science 1964; 145 (3638): 1310-1312
    CrossrefPubMedSearch in Google Scholar
  • 5 Smith SA, Mutch NJ, Baskar D, Rohloff P, Docampo R, Morrissey JH. Polyphosphate modulates blood coagulation and fibrinolysis. Proc Natl Acad Sci U S A 2006; 103 (04) 903-908
    CrossrefPubMedSearch in Google Scholar
  • 6 van der Meijden PEJ, Munnix ICA, Auger JM. , et al. Dual role of collagen in factor XII-dependent thrombus formation. Blood 2009; 114 (04) 881-890
    PubMedSearch in Google Scholar
  • 7 Grover SP, Mackman N. Tissue factor: an essential mediator of hemostasis and trigger of thrombosis. Arterioscler Thromb Vasc Biol 2018; 38 (04) 709-725
    CrossrefPubMedSearch in Google Scholar
  • 8 Wheeler AP, Gailani D. The intrinsic pathway of coagulation as a target for antithrombotic therapy. Hematol Oncol Clin North Am 2016; 30 (05) 1099-1114
    CrossrefPubMedSearch in Google Scholar
  • 9 Duga S, Salomon O. Congenital factor XI deficiency: an update. Semin Thromb Hemost 2013; 39 (06) 621-631
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 He R, Chen D, He S, Factor XI. Factor XI: hemostasis, thrombosis, and antithrombosis. Thromb Res 2012; 129 (05) 541-550
    CrossrefPubMedSearch in Google Scholar
  • 11 Thompson RE, Mandle Jr R, Kaplan AP. Association of factor XI and high molecular weight kininogen in human plasma. J Clin Invest 1977; 60 (06) 1376-1380
    CrossrefPubMedSearch in Google Scholar
  • 12 Wiggins RC, Bouma BN, Cochrane CG, Griffin JH. Role of high-molecular-weight kininogen in surface-binding and activation of coagulation Factor XI and prekallikrein. Proc Natl Acad Sci U S A 1977; 74 (10) 4636-4640
    CrossrefPubMedSearch in Google Scholar
  • 13 Tarumi T, Kravtsov DV, Zhao M, Williams SM, Gailani D. Cloning and characterization of the human factor XI gene promoter: transcription factor hepatocyte nuclear factor 4alpha (HNF-4alpha ) is required for hepatocyte-specific expression of factor XI. J Biol Chem 2002; 277 (21) 18510-18516
    CrossrefPubMedSearch in Google Scholar
  • 14 Zucker M, Hauschner H, Seligsohn U, Rosenberg N. Platelet factor XI: intracellular localization and mRNA splicing following platelet activation. Blood Cells Mol Dis 2018; 69: 30-37
    CrossrefPubMedSearch in Google Scholar
  • 15 Papagrigoriou E, McEwan PA, Walsh PN, Emsley J. Crystal structure of the factor XI zymogen reveals a pathway for transactivation. Nat Struct Mol Biol 2006; 13 (06) 557-558
    CrossrefPubMedSearch in Google Scholar
  • 16 Seligsohn U. Factor XI in haemostasis and thrombosis: past, present and future. Thromb Haemost 2007; 98 (01) 84-89
    Thieme ConnectPubMedSearch in Google Scholar
  • 17 Fujikawa K, Chung DW, Hendrickson LE, Davie EW. Amino acid sequence of human factor XI, a blood coagulation factor with four tandem repeats that are highly homologous with plasma prekallikrein. Biochemistry 1986; 25 (09) 2417-2424
    CrossrefPubMedSearch in Google Scholar
  • 18 Baglia FA, Walsh PN. A binding site for thrombin in the apple 1 domain of factor XI. J Biol Chem 1996; 271 (07) 3652-3658
    CrossrefPubMedSearch in Google Scholar
  • 19 Renné T, Gailani D, Meijers JC, Müller-Esterl W. Characterization of the H-kininogen-binding site on factor XI: a comparison of factor XI and plasma prekallikrein. J Biol Chem 2002; 277 (07) 4892-4899
    CrossrefPubMedSearch in Google Scholar
  • 20 Sun Y, Gailani D. Identification of a factor IX binding site on the third apple domain of activated factor XI. J Biol Chem 1996; 271 (46) 29023-29028
    CrossrefPubMedSearch in Google Scholar
  • 21 Baglia FA, Gailani D, López JA, Walsh PN. Identification of a binding site for glycoprotein Ibalpha in the Apple 3 domain of factor XI. J Biol Chem 2004; 279 (44) 45470-45476
    CrossrefPubMedSearch in Google Scholar
  • 22 Ho DH, Badellino K, Baglia FA, Walsh PN. A binding site for heparin in the apple 3 domain of factor XI. J Biol Chem 1998; 273 (26) 16382-16390
    CrossrefPubMedSearch in Google Scholar
  • 23 Baglia FA, Jameson BA, Walsh PN. Identification and characterization of a binding site for factor XIIa in the Apple 4 domain of coagulation factor XI. J Biol Chem 1993; 268 (06) 3838-3844
    CrossrefPubMedSearch in Google Scholar
  • 24 Meijers JC, Mulvihill ER, Davie EW, Chung DW. Apple four in human blood coagulation factor XI mediates dimer formation. Biochemistry 1992; 31 (19) 4680-4684
    CrossrefPubMedSearch in Google Scholar
  • 25 Bouma BN, Griffin JH. Human blood coagulation factor XI. Purification, properties, and mechanism of activation by activated factor XII. J Biol Chem 1977; 252 (18) 6432-6437
    CrossrefPubMedSearch in Google Scholar
  • 26 Gailani D, Broze Jr GJJ. Factor XI activation in a revised model of blood coagulation. Science 1991; 253 (5022): 909-912
    CrossrefPubMedSearch in Google Scholar
  • 27 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 (12) 7353-7358
    CrossrefPubMedSearch in Google Scholar
  • 28 Lane DA, Philippou H, Huntington JA. Directing thrombin. Blood 2005; 106 (08) 2605-2612
    PubMedSearch in Google Scholar
  • 29 Kannemeier C, Shibamiya A, Nakazawa F. , et al. Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation. Proc Natl Acad Sci U S A 2007; 104 (15) 6388-6393
    CrossrefPubMedSearch in Google Scholar
  • 30 Geng Y, Verhamme IM, Smith SB. , et al. The dimeric structure of factor XI and zymogen activation. Blood 2013; 121 (19) 3962-3969
    CrossrefPubMedSearch in Google Scholar
  • 31 Aktimur A, Gabriel MA, Gailani D, Toomey JR. The factor IX gamma-carboxyglutamic acid (Gla) domain is involved in interactions between factor IX and factor XIa. J Biol Chem 2003; 278 (10) 7981-7987
    CrossrefPubMedSearch in Google Scholar
  • 32 Whelihan MF, Orfeo T, Gissel MT, Mann KG. Coagulation procofactor activation by factor XIa. J Thromb Haemost 2010; 8 (07) 1532-1539
    CrossrefPubMedSearch in Google Scholar
  • 33 Matafonov A, Cheng Q, Geng Y. , et al. Evidence for factor IX-independent roles for factor XIa in blood coagulation. J Thromb Haemost 2013; 11 (12) 2118-2127
    CrossrefPubMedSearch in Google Scholar
  • 34 Puy C, Tucker EI, Matafonov A. , et al. Activated factor XI increases the procoagulant activity of the extrinsic pathway by inactivating tissue factor pathway inhibitor. Blood 2015; 125 (09) 1488-1496
    CrossrefPubMedSearch in Google Scholar
  • 35 Ge X, Yamaguchi Y, Zhao L. , et al. Prochemerin cleavage by factor XIa links coagulation and inflammation. Blood 2018; 131 (03) 353-364
    CrossrefPubMedSearch in Google Scholar
  • 36 Kossmann S, Lagrange J, Jäckel S. , et al. Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension. Sci Transl Med 2017; 9 (375) 9
    PubMedSearch in Google Scholar
  • 37 ten Cate H, Biemond BJ, Levi M. , et al. Factor XIa induced activation of the intrinsic cascade in vivo. Thromb Haemost 1996; 75 (03) 445-449
    Thieme ConnectPubMedSearch in Google Scholar
  • 38 Minnema MC, Friederich PW, Levi M. , et al. Enhancement of rabbit jugular vein thrombolysis by neutralization of factor XI. In vivo evidence for a role of factor XI as an anti-fibrinolytic factor. J Clin Invest 1998; 101 (01) 10-14
    CrossrefPubMedSearch in Google Scholar
  • 39 Mohammed BM, Cheng Q, Matafonov A, Monroe DM, Meijers JCM, Gailani D. Factor XI promotes hemostasis in factor IX-deficient mice. J Thromb Haemost 2018; 16 (10) 2044-2049
    CrossrefPubMedSearch in Google Scholar
  • 40 Wuillemin WA, Hack CE, Bleeker WK, Biemond BJ, Levi M, ten Cate H. Inactivation of factor Xia in vivo: studies in chimpanzees and in humans. Thromb Haemost 1996; 76 (04) 549-555
    Thieme ConnectPubMedSearch in Google Scholar
  • 41 Puy C, Ngo ATP, Pang J. , et al. Endothelial PAI-1 (plasminogen activator inhibitor-1) blocks the intrinsic pathway of coagulation, inducing the clearance and degradation of FXIa (activated factor XI). Arterioscler Thromb Vasc Biol 2019; 39 (07) 1390-1401
    CrossrefPubMedSearch in Google Scholar
  • 42 Björkqvist J, Jämsä A, Renné T. Plasma kallikrein: the bradykinin-producing enzyme. Thromb Haemost 2013; 110 (03) 399-407
    Thieme ConnectPubMedSearch in Google Scholar
  • 43 Fink E, Bhoola KD, Snyman C, Neth P, Figueroa CD. Cellular expression of plasma prekallikrein in human tissues. Biol Chem 2007; 388 (09) 957-963
    PubMedSearch in Google Scholar
  • 44 Hermann A, Arnhold M, Kresse H, Neth P, Fink E. Expression of plasma prekallikrein mRNA in human nonhepatic tissues and cell lineages suggests special local functions of the enzyme. Biol Chem 1999; 380 (09) 1097-1102
    PubMedSearch in Google Scholar
  • 45 McMullen BA, Fujikawa K, Davie EW. Location of the disulfide bonds in human plasma prekallikrein: the presence of four novel apple domains in the amino-terminal portion of the molecule. Biochemistry 1991; 30 (08) 2050-2056
    CrossrefPubMedSearch in Google Scholar
  • 46 Mandle RJ, Colman RW, Kaplan AP. Identification of prekallikrein and high-molecular-weight kininogen as a complex in human plasma. Proc Natl Acad Sci U S A 1976; 73 (11) 4179-4183
    CrossrefPubMedSearch in Google Scholar
  • 47 Motta G, Rojkjaer R, Hasan AA, Cines DB, Schmaier AH. High molecular weight kininogen regulates prekallikrein assembly and activation on endothelial cells: a novel mechanism for contact activation. Blood 1998; 91 (02) 516-528
    CrossrefPubMedSearch in Google Scholar
  • 48 Meloni FJ, Gustafson EJ, Schmaier AH. High molecular weight kininogen binds to platelets by its heavy and light chains and when bound has altered susceptibility to kallikrein cleavage. Blood 1992; 79 (05) 1233-1244
    CrossrefPubMedSearch in Google Scholar
  • 49 Henderson LM, Figueroa CD, Müller-Esterl W, Bhoola KD. Assembly of contact-phase factors on the surface of the human neutrophil membrane. Blood 1994; 84 (02) 474-482
    CrossrefPubMedSearch in Google Scholar
  • 50 Renné T, Dedio J, Meijers JC, Chung D, Müller-Esterl W. Mapping of the discontinuous H-kininogen binding site of plasma prekallikrein. Evidence for a critical role of apple domain-2. J Biol Chem 1999; 274 (36) 25777-25784
    CrossrefPubMedSearch in Google Scholar
  • 51 Li C, Voos KM, Pathak M. , et al. Plasma kallikrein structure reveals apple domain disc rotated conformation compared to factor XI. J Thromb Haemost 2019; 17 (05) 759-770
    CrossrefPubMedSearch in Google Scholar
  • 52 Shariat-Madar Z, Mahdi F, Schmaier AH. Recombinant prolylcarboxypeptidase activates plasma prekallikrein. Blood 2004; 103 (12) 4554-4561
    CrossrefPubMedSearch in Google Scholar
  • 53 Shariat-Madar Z, Mahdi F, Schmaier AH. Identification and characterization of prolylcarboxypeptidase as an endothelial cell prekallikrein activator. J Biol Chem 2002; 277 (20) 17962-17969
    CrossrefPubMedSearch in Google Scholar
  • 54 Joseph K, Tholanikunnel BG, Bygum A, Ghebrehiwet B, Kaplan AP. Factor XII-independent activation of the bradykinin-forming cascade: implications for the pathogenesis of hereditary angioedema types I and II. J Allergy Clin Immunol 2013; 132 (02) 470-475
    CrossrefPubMedSearch in Google Scholar
  • 55 Visser M, van Oerle R, Ten Cate H. , et al. Plasma kallikrein contributes to coagulation in the absence of factor XI by activating factor IX. Arterioscler Thromb Vasc Biol 2020; 40 (01) 103-111
    CrossrefPubMedSearch in Google Scholar
  • 56 Shigematsu S, Ishida S, Gute DC, Korthuis RJ. Bradykinin-induced proinflammatory signaling mechanisms. Am J Physiol Heart Circ Physiol 2002; 283 (06) H2676-H2686
    CrossrefPubMedSearch in Google Scholar
  • 57 Derkx FH, Bouma BN, Schalekamp MP, Schalekamp MA. An intrinsic factor XII- prekallikrein-dependent pathway activates the human plasma renin-angiotensin system. Nature 1979; 280 (5720): 315-316
    CrossrefPubMedSearch in Google Scholar
  • 58 Ichinose A, Fujikawa K, Suyama T. The activation of pro-urokinase by plasma kallikrein and its inactivation by thrombin. J Biol Chem 1986; 261 (08) 3486-3489
    CrossrefPubMedSearch in Google Scholar
  • 59 Irmscher S, Döring N, Halder LD. , et al. Kallikrein cleaves C3 and activates complement. J Innate Immun 2018; 10 (02) 94-105
    CrossrefPubMedSearch in Google Scholar
  • 60 Kaplan AP, Joseph K. The bradykinin-forming cascade and its role in hereditary angioedema. Ann Allergy Asthma Immunol 2010; 104 (03) 193-204
    CrossrefPubMedSearch in Google Scholar
  • 61 Aygören-Pürsün E, Bygum A, Grivcheva-Panovska V. , et al. Oral plasma kallikrein inhibitor for prophylaxis in hereditary angioedema. N Engl J Med 2018; 379 (04) 352-362
    CrossrefPubMedSearch in Google Scholar
  • 62 Banerji A, Busse P, Shennak M. , et al. Inhibiting plasma kallikrein for hereditary angioedema prophylaxis. N Engl J Med 2017; 376 (08) 717-728
    CrossrefPubMedSearch in Google Scholar
  • 63 Federspil G, Vettor R, De Palo E, Padovan D, Sicolo N, Scandellari C. Plasma kallikrein activity in human diabetes mellitus. Metabolism 1983; 32 (06) 540-542
    CrossrefPubMedSearch in Google Scholar
  • 64 Abdulaal M, Haddad NMN, Sun JK, Silva PS. The role of plasma kallikrein-kinin pathway in the development of diabetic retinopathy: pathophysiology and therapeutic approaches. Semin Ophthalmol 2016; 31 (1-2): 19-24
    CrossrefPubMedSearch in Google Scholar
  • 65 Göbel K, Asaridou CM, Merker M. , et al. Plasma kallikrein modulates immune cell trafficking during neuroinflammation via PAR2 and bradykinin release. Proc Natl Acad Sci U S A 2019; 116 (01) 271-276
    CrossrefPubMedSearch in Google Scholar
  • 66 Ottaiano TF, Andrade SS, de Oliveira C. , et al. Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP. Biochimie 2017; 135: 72-81
    CrossrefPubMedSearch in Google Scholar
  • 67 Schapira M, Scott CF, Colman RW. Contribution of plasma protease inhibitors to the inactivation of kallikrein in plasma. J Clin Invest 1982; 69 (02) 462-468
    CrossrefPubMedSearch in Google Scholar
  • 68 Gailani D, Lasky NM, Broze Jr GJJ. A murine model of factor XI deficiency. Blood Coagul Fibrinolysis 1997; 8 (02) 134-144
    CrossrefPubMedSearch in Google Scholar
  • 69 Rosen ED, Gailani D, Castellino FJ. FXI is essential for thrombus formation following FeCl3-induced injury of the carotid artery in the mouse. Thromb Haemost 2002; 87 (04) 774-776
    Thieme ConnectPubMedSearch in Google Scholar
  • 70 Wang X, Cheng Q, Xu L. , et al. Effects of factor IX or factor XI deficiency on ferric chloride-induced carotid artery occlusion in mice. J Thromb Haemost 2005; 3 (04) 695-702
    CrossrefPubMedSearch in Google Scholar
  • 71 Grover SP, Schmedes CM, Auriemma AC. , et al. Differential roles of factors IX and XI in murine placenta and hemostasis under conditions of low tissue factor. Blood Adv 2020; 4 (01) 207-216
    CrossrefPubMedSearch in Google Scholar
  • 72 Wang X, Smith PL, Hsu MY. , et al. Effects of factor XI deficiency on ferric chloride-induced vena cava thrombosis in mice. J Thromb Haemost 2006; 4 (09) 1982-1988
    CrossrefPubMedSearch in Google Scholar
  • 73 Tucker EI, Marzec UM, White TC. , et al. Prevention of vascular graft occlusion and thrombus-associated thrombin generation by inhibition of factor XI. Blood 2009; 113 (04) 936-944
    CrossrefPubMedSearch in Google Scholar
  • 74 Crosby JR, Marzec U, Revenko AS. , et al. Antithrombotic effect of antisense factor XI oligonucleotide treatment in primates. Arterioscler Thromb Vasc Biol 2013; 33 (07) 1670-1678
    CrossrefPubMedSearch in Google Scholar
  • 75 Bird JE, Smith PL, Wang X. , et al. Effects of plasma kallikrein deficiency on haemostasis and thrombosis in mice: murine ortholog of the Fletcher trait. Thromb Haemost 2012; 107 (06) 1141-1150
    Thieme ConnectPubMedSearch in Google Scholar
  • 76 Kokoye Y, Ivanov I, Cheng Q. , et al. A comparison of the effects of factor XII deficiency and prekallikrein deficiency on thrombus formation. Thromb Res 2016; 140: 118-124
    CrossrefPubMedSearch in Google Scholar
  • 77 Göb E, Reymann S, Langhauser F. , et al. Blocking of plasma kallikrein ameliorates stroke by reducing thromboinflammation. Ann Neurol 2015; 77 (05) 784-803
    CrossrefPubMedSearch in Google Scholar
  • 78 Stavrou EX, Fang C, Merkulova A. , et al. Reduced thrombosis in Klkb1-/- mice is mediated by increased Mas receptor, prostacyclin, Sirt1, and KLF4 and decreased tissue factor. Blood 2015; 125 (04) 710-719
    CrossrefPubMedSearch in Google Scholar
  • 79 Revenko AS, Gao D, Crosby JR. , et al. Selective depletion of plasma prekallikrein or coagulation factor XII inhibits thrombosis in mice without increased risk of bleeding. Blood 2011; 118 (19) 5302-5311
    PubMedSearch in Google Scholar
  • 80 Adams GN, LaRusch GA, Stavrou E. , et al. Murine prolylcarboxypeptidase depletion induces vascular dysfunction with hypertension and faster arterial thrombosis. Blood 2011; 117 (14) 3929-3937
    CrossrefPubMedSearch in Google Scholar
  • 81 Rosenthal RL, Dreskin OH, Rosenthal N. New hemophilia-like disease caused by deficiency of a third plasma thromboplastin factor. Proc Soc Exp Biol Med 1953; 82 (01) 171-174
    CrossrefPubMedSearch in Google Scholar
  • 82 Santoro C, Di Mauro R, Baldacci E. , et al. Bleeding phenotype and correlation with factor XI (FXI) activity in congenital FXI deficiency: results of a retrospective study from a single centre. Haemophilia 2015; 21 (04) 496-501
    CrossrefPubMedSearch in Google Scholar
  • 83 Bolton-Maggs PH, Patterson DA, Wensley RT, Tuddenham EG. Definition of the bleeding tendency in factor XI-deficient kindreds--a clinical and laboratory study. Thromb Haemost 1995; 73 (02) 194-202
    Thieme ConnectPubMedSearch in Google Scholar
  • 84 Yang DT, Flanders MM, Kim H, Rodgers GM. Elevated factor XI activity levels are associated with an increased odds ratio for cerebrovascular events. Am J Clin Pathol 2006; 126 (03) 411-415
    CrossrefPubMedSearch in Google Scholar
  • 85 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 (10) 696-701
    CrossrefPubMedSearch in Google Scholar
  • 86 Siegerink B, Govers-Riemslag JW, Rosendaal FR, Ten Cate H, Algra A. Intrinsic coagulation activation and the risk of arterial thrombosis in young women: results from the risk of arterial thrombosis in relation to oral contraceptives (RATIO) case-control study. Circulation 2010; 122 (18) 1854-1861
    CrossrefPubMedSearch in Google Scholar
  • 87 Salomon O, Steinberg DM, Koren-Morag N, Tanne D, Seligsohn U. Reduced incidence of ischemic stroke in patients with severe factor XI deficiency. Blood 2008; 111 (08) 4113-4117
    CrossrefPubMedSearch in Google Scholar
  • 88 Salomon O, Steinberg DM, Zucker M, Varon D, Zivelin A, Seligsohn U. Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis. Thromb Haemost 2011; 105 (02) 269-273
    Thieme ConnectPubMedSearch in Google Scholar
  • 89 Preis M, Hirsch J, Kotler A. , et al. Factor XI deficiency is associated with lower risk for cardiovascular and venous thromboembolism events. Blood 2017; 129 (09) 1210-1215
    CrossrefPubMedSearch in Google Scholar
  • 90 Kyrle PA, Eischer L, Šinkovec H, Eichinger S. Factor XI and recurrent venous thrombosis: an observational cohort study. J Thromb Haemost 2019; 17 (05) 782-786
    CrossrefPubMedSearch in Google Scholar
  • 91 Salomon O, Steinberg DM, Dardik R. , et al. Inherited factor XI deficiency confers no protection against acute myocardial infarction. J Thromb Haemost 2003; 1 (04) 658-661
    CrossrefPubMedSearch in Google Scholar
  • 92 Doggen CJ, Rosendaal FR, Meijers JC. Levels of intrinsic coagulation factors and the risk of myocardial infarction among men: opposite and synergistic effects of factors XI and XII. Blood 2006; 108 (13) 4045-4051
    PubMedSearch in Google Scholar
  • 93 Minnema MC, Peters RJ, de Winter R. , et al. Activation of clotting factors XI and IX in patients with acute myocardial infarction. Arterioscler Thromb Vasc Biol 2000; 20 (11) 2489-2493
    CrossrefPubMedSearch in Google Scholar
  • 94 Govers-Riemslag JWP, Smid M, Cooper JA. , et al. The plasma kallikrein-kinin system and risk of cardiovascular disease in men. J Thromb Haemost 2007; 5 (09) 1896-1903
    CrossrefPubMedSearch in Google Scholar
  • 95 Loeffen R, van Oerle R, de Groot PG. , et al. Increased factor XIa levels in patients with a first acute myocardial infarction: the introduction of a new thrombin generation based factor XIa assay. Thromb Res 2014; 134 (06) 1328-1334
    CrossrefPubMedSearch in Google Scholar
  • 96 Hathaway WE, Belhasen LP, Hathaway HS. Evidence for a new plasma thromboplastin factor. I. Case report, coagulation studies and physicochemical properties. Blood 1965; 26 (05) 521-532
    CrossrefPubMedSearch in Google Scholar
  • 97 Girolami A, Scarparo P, Candeo N, Lombardi AM. Congenital prekallikrein deficiency. Expert Rev Hematol 2010; 3 (06) 685-695
    CrossrefPubMedSearch in Google Scholar
  • 98 Girolami A, Candeo N, De Marinis GB, Bonamigo E, Girolami B. Comparative incidence of thrombosis in reported cases of deficiencies of factors of the contact phase of blood coagulation. J Thromb Thrombolysis 2011; 31 (01) 57-63
    CrossrefPubMedSearch in Google Scholar
  • 99 Girolami A, Ferrari S, Cosi E, Girolami B. Cardiovascular diseases in congenital prekallikrein deficiency: comparison with other chance-associated morbidities. Blood Coagul Fibrinolysis 2018; 29 (05) 423-428
    CrossrefPubMedSearch in Google Scholar
  • 100 Merlo C, Wuillemin WA, Redondo M. , et al. Elevated levels of plasma prekallikrein, high molecular weight kininogen and factor XI in coronary heart disease. Atherosclerosis 2002; 161 (02) 261-267
    CrossrefPubMedSearch in Google Scholar
  • 101 Folsom AR, Tang W, Basu S. , et al. Plasma concentrations of high molecular weight kininogen and prekallikrein and venous thromboembolism incidence in the general population. Thromb Haemost 2019; 119 (05) 834-843
    Thieme ConnectPubMedSearch in Google Scholar
  • 102 Mackman N, Bergmeier W, Stouffer GA, Weitz JI. Therapeutic strategies for thrombosis: new targets and approaches. Nat Rev Drug Discov 2020; 19 (05) 333-352
    CrossrefPubMedSearch in Google Scholar
  • 103 Thomas D, Thelen K, Kraff S. , et al. BAY 1213790, a fully human IgG1 antibody targeting coagulation factor XIa: first evaluation of safety, pharmacodynamics, and pharmacokinetics. Res Pract Thromb Haemost 2019; 3 (02) 242-253
    CrossrefPubMedSearch in Google Scholar
  • 104 Koch AW, Schiering N, Melkko S. , et al. MAA868, a novel FXI antibody with a unique binding mode, shows durable effects on markers of anticoagulation in humans. Blood 2019; 133 (13) 1507-1516
    CrossrefPubMedSearch in Google Scholar
  • 105 van Montfoort ML, Knaup VL, Marquart JA. , et al. Two novel inhibitory anti-human factor XI antibodies prevent cessation of blood flow in a murine venous thrombosis model. Thromb Haemost 2013; 110 (05) 1065-1073
    Thieme ConnectPubMedSearch in Google Scholar
  • 106 Bennett CF, Swayze EE. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu Rev Pharmacol Toxicol 2010; 50: 259-293
    CrossrefPubMedSearch in Google Scholar
  • 107 Büller HR, Bethune C, Bhanot S. , et al; FXI-ASO TKA Investigators. Factor XI antisense oligonucleotide for prevention of venous thrombosis. N Engl J Med 2015; 372 (03) 232-240
    CrossrefPubMedSearch in Google Scholar
  • 108 Zhang H, Löwenberg EC, Crosby JR. , et al. Inhibition of the intrinsic coagulation pathway factor XI by antisense oligonucleotides: a novel antithrombotic strategy with lowered bleeding risk. Blood 2010; 116 (22) 4684-4692
    PubMedSearch in Google Scholar
  • 109 Perera V, Luettgen JM, Wang Z. , et al. First-in-human study to assess the safety, pharmacokinetics and pharmacodynamics of BMS-962212, a direct, reversible, small molecule factor XIa inhibitor in non-Japanese and Japanese healthy subjects. Br J Clin Pharmacol 2018; 84 (05) 876-887
    CrossrefPubMedSearch in Google Scholar
  • 110 U.S. National Library of Medicine. A two-part study to assess the safety, tolerability, PK and PD of ONO-7684 in healthy adult volunteers. 2019 . Available at: https://clinicaltrials.gov/ct2/show/NCT03919890 . Accessed January 6, 2020
    PubMedSearch in Google Scholar
  • 111 U.S. National Library of Medicine. A study on BMS-986177 for the prevention of a stroke in patients receiving aspirin and clopidogrel (AXIOMATIC-SSP). 2018 . Available at: https://clinicaltrials.gov/ct2/show/NCT03766581 . Accessed January 6, 2020
    PubMedSearch in Google Scholar
  • 112 U.S. National Library of Medicine. A study of JNJ-70033093 (BMS-986177) versus subcutaneous enoxaparin in participants undergoing elective total knee replacement surgery (AXIOMATIC-TKR). 2019 . Available at: https://clinicaltrials.gov/ct2/show/NCT03891524 . Accessed January 6, 2020
    PubMedSearch in Google Scholar
  • 113 Medicine USNLo. Study to gather information about the proper dosing of the oral FXIa inhibitor BAY 2433334 and to compare the safety of the study drug to apixaban, a non-vitamin K oral anticoagulant (NOAC) in patients with irregular heartbeat (atrial fibrillation) that can lead to heart-related complications. (PACIFIC-AF). 2020 . Available at: https://www.clinicaltrials.gov/ct2/show/NCT04218266 . Accessed January 14, 2020
    PubMedSearch in Google Scholar
  • 114 Cicardi M, Levy RJ, McNeil DL. , et al. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med 2010; 363 (06) 523-531
    CrossrefPubMedSearch in Google Scholar
  • 115 Weitz JI, Bauersachs R, Becker B. , et al. Effect of osocimab in preventing venous thromboembolism among patients undergoing knee arthroplasty: the FOXTROT randomized clinical trial. JAMA 2020; 323 (02) 130-139
    CrossrefPubMedSearch in Google Scholar