Thrombosis and Haemostasis, Table of Contents Thromb Haemost 2002; 87(04): 563-574DOI: 10.1055/s-0037-1613050 Review Article Schattauer GmbH Mouse Models in Coagulation Kelly A. Hogan 1 Department of Pathology and Laboratory Medicine , Harmut Weiler 2 The Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, Wisconsin, USA , Susan T. Lord 1 Department of Pathology and Laboratory Medicine 3 Curriculum in Genetics and Molecular Biology, Chapel Hill, NC 4 Department of Chemistry, University of North Carolina, Chapel Hill, NC › Author Affiliations Recommend Article Abstract Buy Article Keywords KeywordsGene-targeting - mice - hemostasis - thrombosis - vasculogenesis Full Text References References 1 O’Reilly MS, Pirie-Shepherd S, Lane WS, Folkman J. Antiangiogenic activity of the cleaved conformation of the serpin antithrombin. Science 1999; 285: 1926-8. 2 Hogan B, Beddington R, Costantini F, Lacy E. Manipulating the Mouse Embryo. A laboratory Manual. Plainview, NY: Cold Spring Harbor Laboratory Press; 1994 3 Bugge TH, Xiao Q, Kombrinck KW, Flick MJ, Holmback K, Danton MJ, Colbert MC, Witte DP, Fujikawa K, Davie EW. Fatal embryonic bleeding events in mice lacking tissue factor, the cell-associated initiator of blood coagulation. Proc Natl Acad Sci USA 1996; 93: 6258-63. 4 Carmeliet P, Mackman N, Moons L, Luther T, Gressens P, Van Vlaenderen I, Demunck H, Kasper M, Breier G, Evrard P, Muller M, Risau W, Edgington T, Collen D. Role of tissue factor in embryonic blood vessel development. Nature 1996; 383: 73-5. 5 Toomey JR, Kratzer KE, Lasky NM, Stanton JJ, Broze Jr GJ. Targeted disruption of the murine tissue factor gene results in embryonic lethality. Blood 1996; 88: 1583-7. 6 Parry GCN, Erlich JH, Carmeliet P, Luther T, Mackman N. Low levels of tissue factor are compatible with development and hemostasis in mice. J Clin Invest 1998; 101: 560-9. 7 Chen J, Bierhaus A, Schiekofer S, Andrassy M, Chen B, Stern DM, Nawroth PP. Tissue factor – a receptor involved in the control of cellular properties, including angiogenesis. Thromb Haemost 2001; 86: 334-45. 8 Ruf W, Mueller BM. Tissue factor signaling. Thromb Haemost 1999; 82: 175-82. 9 Parry GCN, Mackman N. Mouse embryogenesis requires the tissue factor extracellular domain but not the cytoplasmic domain. J Clin Invest 2000; 105: 1547-54. 10 Ruf W, Fischer EG, Huang HY, Miyagi Y, Ott I, Riewald M, Mueller BM. Diverse functions of protease receptor tissue factor in inflammation and metastasis. Immunol Res 2000; 21: 289-92. 11 Mackman N. Regulation of the tissue factor gene. Thromb Haemost 1997; 78: 747-54. 12 Ott I, Fischer EG, Miyagi Y, Mueller BM, Ruf W. A role for tissue factor in cell adhesion and migration mediated by interaction with actin-binding protein 280. J Cell Biol 1998; 140: 1241-53. 13 Rosen ED, Chan JC, Idusogie E, Clotman F, Vlasuk G, Luther T, Jalbert LR, Albrecht S, Zhong L, Lissens A, Schoonjans L, Moons L, Collen D, Castellino FJ, Carmeliet P. Mice lacking factor VII develop normally but suffer fatal perinatal bleeding. Nature 1997; 390: 290-4. 14 Yang TL, Cui J, Taylor JM, Yang A, Gruber SB, Ginsburg D. Rescue of fatal neonatal hemorrhage in factor V deficient mice by low level transgene expression. Thromb Haemost 2001; 83: 70-7. 15 Luther T, Flossel C, Mackman N, Bierhaus A, Kasper M, Albrecht S, Sage EH, Iruela-Arispe L, Grossmann H, Strohlein A, Zhang Y, Nawroth PP, Carmeliet P, Loskutoff DJ, Muller M. Tissue factor expression during human and mouse development. Am J Pathol 1996; 149: 101-13. 16 Cooper DN, Millar DS, Wacey A, Banner DW, Tuddenham EG. Inherited factor VII deficiency: molecular genetics and pathophysiology. Thromb Haemost 1997; 78: 151-60. 17 Dewerchin M, Liang Z, Moons L, Carmeliet P, Castellino FJ, Collen D, Rosen ED. Blood coagulation factor X deficiency causes partial embryonic lethality and fatal neonatal bleeding in mice. Thromb Haemost 2000; 83: 185-90. 18 Cui J, O’Shea KS, Purkayastha A, Saunders TL, Ginsburg D. Fatal haemorrhage and incomplete block to embryogenesis in mice lacking coagulation factor V. Nature 1996; 384: 66-8. 19 Sun WY, Witte DP, Degen JL, Colbert MC, Burkart MC, Holmback K, Xiao Q, Bugge TH, Degen SJ. Prothrombin deficiency results in embryonic and neonatal lethality in mice. Proc Natl Acad Sci USA 1998; 95: 7597-602. 20 Xue J, Wu Q, Westfield LA, Tuley EA, Lu D, Zhang Q, Shim K, Zheng X, Sadler JE. Incomplete embryonic lethality and fatal neonatal hemorrhage caused by prothrombin deficiency in mice. Proc Natl Acad Sci USA 1998; 95: 7603-7. 21 Ong K, Horsfall W, Conway EM, Schuh AC. Early embryonic expression of murine coagulation system components. Thromb Haemost 2000; 84: 1023-30. 22 Lin HF, Maeda N, Smithies O, Straight DL, Stafford DW. A coagulation factor IX-deficient mouse model for human hemophilia B. Blood 1997; 90: 3962-6. 23 Bi L, Lawler AM, Antonarakis SE, High KA, Gearhart JD, Kazazian Jr HH. Targeted disruption of the mouse factor VIII gene produces a model of haemophilia A. Nat Genet 1995; 10: 119-21. 24 Bi L, Sarkar R, Naas T, Lawler AM, Pain J, Shumaker SL, Bedian V, Kazazian Jr HH. Further characterization of factor VIII-deficient mice created by gene targeting: RNA and protein studies. Blood 1996; 88: 3446-50. 25 High KA, Roberts HR. FIX. In: Molecular Basis of Thrombosis and Hemostasis. High KA, Roberts HR. eds. New York: Marcel Dekker, Inc; 1995: 215-37. 26 Fakharzadeh SS, Zhang Y, Sarkar R, Kazazian Jr HH. Correction of the coagulation defect in hemophilia A mice through factor VIII expression in skin. Blood 2000; 95: 2799-805. 27 Kung SH, Hagstrom JN, Cass D, Tai SJ, Lin HF, Stafford DW, High KA. Human factor IX corrects the bleeding diathesis of mice with hemophilia B. Blood 1998; 91: 784-90. 28 Chuah MK, Collen D, VandenDriessche T. Gene therapy for hemophilia. J Gene Med 2001; 03: 3-20. 29 Hassan HJ, Leonardi A, Chelucci C, Mattia G, Macioce G, Guerriero R, Russo G, Mannucci PM, Peschle C. Blood coagulation factors in human embryonic-fetal development: preferential expression of the FVII/tissue factor pathway. Blood 1990; 76: 1158-64. 30 Gailani D, Lasky NM, Broze Jr GJ. A murine model of factor XI deficiency. Blood Coagul Fibrinol 1997; 08: 134-44. 31 Gailani D, Sun MF, Sun Y. A comparison of murine and human factor XI. Blood 1997; 90: 1055-64. 32 Bloom AL. Inherited disorders of blood coagulation. In: Haemostasis and Thrombosis. Bloom AL, Thomas DP. eds. New York: Churchill Livingstone; 1981: 321-70. 33 Bouma BN, Meijers JC. Role of blood coagulation factor XI in downregulation of fibrinolysis. Curr Opin Hematol 2000; 07: 266-72. 34 von dem Borne PA, Meijers JC, Bouma BN. Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis. Blood 1995; 86: 3035-42. 35 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: 696-701. 36 Roberts HR, White Jr GC. Inherited disorders of prothrombin conversion. In: Hemostasis and Thrombosis Basic Principles and Clinical Practice. Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN. eds. Philadelphia: Lippincott Williams and Wilkins; 2001: 839-53. 37 Degen SJF. Prothrombin. In: Molecular Basis of Thrombosis and Hemostasis. High KA, Roberts HR. eds. New York: Marcel Dekker, Inc; 1995: 75-99. 38 Suh TT, Holmback K, Jensen NJ, Daugherty CC, Small K, Simon DI, Potter S, Degen JL. Resolution of spontaneous bleeding events but failure of pregnancy in fibrinogen-deficient mice. Genes Dev 1995; 09: 2020-33. 39 Ploplis VA, Wilberding J, McLennan L, Liang Z, Cornelissen I, DeFord ME, Rosen ED, Castellino FJ. A total fibrinogen deficiency is compatible with the development of pulmonary fibrosis in mice. Am J Pathol 2000; 157: 703-8. 40 Shivdasani RA, Rosenblatt MF, Zucker-Franklin D, Jackson CW, Hunt P, Saris CJ, Orkin SH. Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development. Cell 1995; 81: 695-704. 41 Coughlin SR. How the protease thrombin talks to cells. Proc Natl Acad Sci USA 1999; 96: 11023-7. 42 Connolly AJ, Ishihara H, Kahn ML, Farese RVJ, Coughlin SR. Role of the thrombin receptor in development and evidence for a second receptor. Nature 1996; 381: 516-9. 43 Griffen CT, Srinivasan Y, Zheng YW, Huang W, Coughlin SR. A role for thrombin receptor signaling in endothelial cells during embryonic development. Science 2001; 293: 1666-70. 44 Coughlin SR. Thrombin signalling and protease-activated receptors. Nature 2000; 407: 258-64. 45 Soifer SJ, Peters KG, O’Keefe J, Coughlin SR. Disparate temporal expression of the prothrombin and thrombin receptor genes during mouse development. Am J Pathol 1994; 144: 60-9. 46 Camerer E, Huang W, Coughlin SR. Tissue factor-and factor X-dependent activation of protease-activated receptor 2 by factor VIIa. Proc Natl Acad Sci USA 2000; 97: 5255-60. 47 Ollivier V, Chabbat J, Herbert JM, Hakim J, de Prost D. Vascular endothelial growth factor production by fibroblasts in response to factor VIIa binding to tissue factor involves thrombin and factor Xa. Arterioscler Thromb Vasc Biol 2000; 20: 1374-81. 48 Clauss M, Grell M, Fangmann C, Fiers W, Scheurich P, Risau W. Synergistic induction of endothelial tissue factor by tumor necrosis factor and vascular endothelial growth factor: functional analysis of the tumor necrosis factor receptors. FEBS Letters 1996; 390: 334-8. 49 Clauss M, Gerlach M, Gerlach H, Brett J, Wang F, Familletti PC, Pan YC, Olander JV, Connolly DT, Stern D. Vascular permeability factor: a tumorderived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med 1990; 172: 1535-45. 50 Zucker S, Mirza H, Conner CE, Lorenz AF, Drews MH, Bahou WF, Jesty J. Vascular endothelial growth factor induces tissue factor and matrix metalloproteinase production in endothelial cells: conversion of prothrombin to thrombin results in progelatinase A activation and cell proliferation. Int J Cancer 1998; 75: 780-6. 51 Takano S, Tsuboi K, Tomono Y, Mitsui Y, Nose T. Tissue factor, osteopontin, alphavbeta3 integrin expression in microvasculature of gliomas associated with vascular endothelial growth factor expression. Br J Cancer 1967; 82: 1967-73. 52 Abe K, Shoji M, Chen J, Bierhaus A, Danave I, Micko C, Casper K, Dillehay DL, Nawroth PP, Rickles FR. Regulation of vascular endothelial growth factor production and angiogenesis by the cytoplasmic tail of tissue factor. Proc Natl Acad Sci USA 1999; 96: 8663-8. 53 Zhang Y, Deng Y, Luther T, Muller M, Ziegler R, Waldherr R, Stern DM, Nawroth PP. Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. J Clin Invest 1994; 94: 1320-7. 54 Tsopanoglou NE, Maragoudakis ME. On the mechanism of thrombininduced angiogenesis. Potentiation of vascular endothelial growth factor activity on endothelial cells by up-regulation of its receptors. J Biol Chem 1999; 274: 23969-76. 55 Ni H, Denis CV, Subbarao S, Degen JL, Sato TN, Hynes RO, Wagner DD. Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen. J Clin Invest 2000; 106: 385-92. 56 Bugge TH, Flick MJ, Daugherty CC, Degen JL. Plasminogen deficiency causes severe thrombosis but is compatible with development and reproduction. Genes Dev 1995; 09: 794-807. 57 Ploplis VA, Carmeliet P, Vazirzadeh S, Van Vlaenderen I, Moons L, Plow EF, Collen D. Effects of disruption of the plasminogen gene on thrombosis, growth, and health in mice. Circulation 1995; 92: 2585-93. 58 Ploplis VA. Gene targeting in hemostasis. Plasminogen. Front Biosci 2001; 06: D555-69. 59 Carmeliet P, Moons L, Ploplis VA, Plow E, Collen D. Impaired arterial neointima formation in mice with disruption of the plasminogen gene. J Clin Invest 1997; 99: 200-8. 60 Romer J, Bugge TH, Pyke C, Lund LR, Flick MJ, Degen JL, Dano K. Impaired wound healing in mice with a disrupted plasminogen gene. Nat Med 1996; 02: 287-92. 61 Drew AF, Kaufman AH, Kombrinck KW, Danton MJS, Daugherty CC, Degen JL, Bugge TH. Ligneous conjunctivitis in plasminogen-deficient mice. Blood 1998; 91: 1616-24. 62 Bugge TH, Kombrinck KW, Flick MJ, Daugherty CC, Danton MJ, Degen JL. Loss of fibrinogen rescues mice from the pleiotropic effects of plasminogen deficiency. Cell 1996; 87: 709-19. 63 Bezerra JA, Bugge TH, Melin-Aldana H, Sabla G, Kombrinck KW, Witte DP, Degen JL. Plasminogen deficiency leads to impaired remodeling after a toxic injury to the liver. Proc Natl Acad Sci USA 1999; 96: 15143-8. 64 Holmback K, Danton MJ, Suh TT, Daugherty CC, Degen JL. Impaired platelet aggregation and sustained bleeding in mice lacking the fibrinogen motif bound by integrin alpha IIb beta 3. EMBO J 1996; 15: 5760-71. 65 Hogan KA, Maeda N, Kluckman KD, Lord ST. Synthesis of a mouse model of the dysfibrinogen Vlissingen/Frankfurt IV. Ann NY Acad Sci 2001; 936: 117-21. 66 Gulledge AA, Rezaee F, Verheijen JH, Lord ST. A novel transgenic mouse model of hyperfibrinogenemia. Thromb Haemost 2001; 86: 511-6. 67 Denis C, Methia N, Frenette PS, Rayburn H, Ullman-Cullere M, Hynes RO, Wagner DD. A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis. Proc Natl Acad Sci USA 1998; 95: 9524-9. 68 Subramaniam M, Frenette PS, Saffaripour S, Johnson RC, Hynes RO, Wagner DD. Defects in hemostasis in P-selectin-deficient mice. Blood 1996; 87: 1238-42. 69 Frenette PS, Johnson RC, Hynes RO, Wagner DD. Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci USA 1995; 92: 7450-4. 70 Romo GM, Dong JF, Schade AJ, Gardiner EE, Kansas GS, Li CQ, McIntire LV, Berndt MC, Lopez JA. The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin. J Exp Med 1999; 190: 803-14. 71 Denis CV, Andre P, Saffaripour S, Wagner DD. Defect in regulated secretion of P-selectin affects leukocyte recruitment in von Willebrand factordeficient mice. Proc Natl Acad Sci USA 2001; 98: 4072-7. 72 Methia N, Andre P, Denis CV, Economopoulos M, Wagner DD. Localized reduction of atherosclerosis in von Willebrand factor-deficient mice. Blood 2001; 98: 1424-8. 73 Duga S, Asselta R, Santagostino E, Zeinali S, Simonic T, Malcovati M, Mannucci PM, Tenchini ML. Missense mutations in the human f3 fibrinogen gene cause congenital afibrinogenemia by impairing fibrinogen secretion. Blood 2000; 95: 1336-41. 74 Neerman-Arbez M, Honsberger A, Antonarakis SE, Morris MA. Deletion of the fibrinogen alpha-chain gene (FGA) causes congenital afibrinogenemia. J Clin Invest 1999; 103: 215-8. 75 Lak M, Keihani M, Elahi F, Peyvandi F, Mannucci PM. Bleeding and thrombosis in 55 patients with inherited afibrinogenaemia. Br J Haematol 1999; 107: 204-6. 76 Montgomery RR. Structure and function of von Willebrand Factor. In: Hemostasis and Thrombosis Basic Principles and Clinical Practices. Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN. eds. Philadelphia: Lippincott Williams and Wilkins; 2001: 250-74. 77 Cronin C, Fitzpatrick D, Temperley I. Multiple pulmonary emboli in a patient with afibrinogenaemia. Acta Haematol 1988; 79: 53-4. 78 Ingram GI, McBrien DJ, Spencer H. Fatal pulmonary embolus in congenital fibropenia. Report of two cases. Acta Haematol 1966; 35: 56-62. 79 Hodivala-Dilke KM, McHugh KP, Tsakiris DA, Rayburn H, Crowley D, Ullman-Cullere M, Ross FP, Coller BS, Teitelbaum S, Hynes RO. Beta3-integrin deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival. J Clin Invest 1999; 103: 229-38. 80 Ni H, Ramakrishnan V, Ruggeri ZM, Papalia JM, Phillips DR, Wagner DD. Increased thrombogenesis and embolus formation in mice lacking glycoprotein V. Blood 2001; 98: 368-73. 81 Green FR. Taking the hype out of hyperfibrinogenemia. Thromb Haemost 2001; 86: 509-10. 82 Xiao Q, Danton MS, Witte DP, Kowala MC, Valentine MT, Degen JL. Fibrinogen deficiency is compatible with the development of atherosclerosis in mice. J Clin Invest 1998; 101: 1184-94. 83 Lou XJ, Boonmark NW, Horrigan FT, Degen JL, Lawn RM. Fibrinogen deficiency reduces vascular accumulation of apolipoprotein(a) and developmentof atherosclerosis in apolipoprotein (a) transgenic mice. Proc Natl Acad Sci USA 1998; 95: 12591-5. 84 Huang ZF, Higuchi D, Lasky N, Broze Jr GJ. Tissue factor pathway inhibitor gene disruption produces intrauterine lethality in mice. Blood 1997; 90: 944-51. 85 Huang ZF, Broze Jr G. Consequences of tissue factor pathway inhibitor gene-disruption in mice. Thromb Haemost 1997; 78: 699-704. 86 Chan JC, Carmeliet P, Moons L, Rosen ED, Huang ZF, Broze Jr GJ, Collen D, Castellino FJ. Factor VII deficiency rescues the intrauterine lethality in mice associated with a tissue factor pathway inhibitor deficit. J Clin Invest 1999; 103: 475-82. 87 Healy AM, Rayburn HB, Rosenberg RD, Weiler H. Absence of the bloodclotting regulator thrombomodulin causes embryonic lethality in mice before development of a functional cardiovascular system. Proc Natl Acad Sci USA 1995; 92: 850-4. 88 Rosenberg RD. Thrombomodulin gene disruption and mutation in mice. Thromb Haemost 1997; 78: 705-9. 89 Conway EM, Pollefeyt S, Cornelissen J, DeBaere I, Steiner-Mosonyi M, Weitz JI, Weiler-Guettler H, Carmeliet P, Collen D. Structure-function analyses of thrombomodulin by gene-targeting in mice: the cytoplasmic domain is not required for normal fetal development. Blood 1999; 93: 3442-50. 90 Isermann B, Hendrickson SB, Hutley K, Wing M, Weiler H. Tissuerestricted expression of thrombomodulin in the placenta rescues thrombo-modulin-deficient mice from early lethality and reveals a secondary developmental block. Development 2001; 128: 827-38. 91 Weiler-Guettler H, Christie PD, Beeler DL, Healy AM, Hancock WW, Rayburn H, Edelberg JM, Rosenberg RD. A targeted point mutation in thrombomodulin generates viable mice with a prethrombotic state. J Clin Invest 1998; 101: 1983-91. 92 Weiler H, Lindner V, Kerlin B, Isermann BH, Hendrickson SB, Cooley BC, Meh DA, Mosesson MW, Shworak NW, Post MJ, Conway EM, Ulf-man LH, von Andrian UH, Weitz JI. Characterization of a mouse model for thrombomodulin deficiency. Arterioscler Thromb Vasc Biol 2001; 21: 1531-7. 93 Isermann B, Hendrickson SB, Zogg M, Wing M, Cummiskey M, Kisanuki YY, Yanagisawa M, Weiler H. Endothelium-specific loss of murine thrombomodulin disrupts the protein C anticoagulant pathway and causes juvenile-onset thrombosis. J Clin Invest 2001; 108: 537-46. 94 Jalbert LR, Rosen ED, Moons L, Chan JC, Carmeliet P, Collen D, Castellino FJ. Inactivation of the gene for anticoagulant protein C causes lethal perinatal consumptive coagulopathy in mice. J Clin Invest 1998; 102: 1481-8. 95 Chan JC, Cornelissen I, Collen D, Ploplis VA, Castellino FJ. Combined factor VII/protein C deficiency results in intrauterine coagulopathy in mice. J Clin Invest 2000; 105: 897-903. 96 Chan JC, Ganopolsky JG, Cornelissen I, Suckow MA, Sandoval-Coope MJ, Brown EC, Noria F, Gailani D, Rosen ED, Ploplis VA, Castellino F. The characterization of mice with a targeted combined deficiency of protein C and factor XI. Am J Pathol 2001; 158: 469-79. 97 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: 64-7. 98 van der Meer FJ, Koster T, Vandenbroucke JP, Briet E, Rosendaal FR. The Leiden Thrombophilia Study (LETS). Thromb Haemost 1997; 78: 631-5. 99 Cui J, Eitzman DT, Westrick RJ, Christie PD, Xu ZJ, Yang AY, Purkayastha AATLY, Metz AL, Gallagher KP, Tyson JA, Rosenverg RD, Ginsburg D. Spontaneous thrombosis in mice carrying the factor V Leiden mutation. Blood 2000; 96: 4222-6. 100 Ishiguro K, Kojima T, Kadomatsu K, Nakayama Y, Takagi A, Suzuki M, Takeda N, Ito M, Yamamoto K, Matsushita T, Kusugami K, Muramatsu T, Saito H. Complete antithrombin deficiency in mice results in embryonic lethality. J Clin Invest 2000; 106: 873-8. 101 Yin ZF, Huang ZF, Cui J, Fiehler R, Lasky N, Ginsburg D, GJ Jr. Prothrombotic phenotype of protein Z deficiency. Proc Natl Acad Sci USA 2000; 97: 6734-8. 102 Broze Jr GJ. Protein-Z and thrombosis. Lancet 2001; 357: 900-1. 103 Vasse M, Guegan-Massardier E, Borg JY, Woimant F, Soria C. Frequency of protein Z deficiency in patients with ischaemic stroke. Lancet 2001; 357: 933-4. 104 Berdeaux DH, Abshire TC, Marlar RA. Dysfunctional protein C deficiency (type II). A report of 11 cases in 3 American families and review of the literature. Am J Clin Pathol 1993; 99: 677-86. 105 Nizzi Jr FA, Kaplan HS. Protein C and S deficiency. Semin Thromb Hemost 1999; 25: 265-72. 106 Ohlin AK, Marlar RA. The first mutation identified in the thrombomodulin gene in a 45-year-old man presenting with thromboembolic disease. Blood 1995; 85: 330-6. 107 Ohlin AK, Marlar RA. Thrombomodulin gene defects in families with thromboembolic disease – a report on four families. Thromb Haemost 1999; 81: 338-44. 108 Salomaa V, Matei C, Aleksic N, Sansores-Garcia L, Folsom AR, Juneja H, Chambless LE, Wu KK. Soluble thrombomodulin as a predictor of incident coronary heart disease and symptomless carotid artery atherosclerosis in the Atherosclerosis Risk in Communities (ARIC) Study: a case-cohort study. Lancet 1999; 353: 1729-34. 109 Norlund L, Zoller B, Ohlin AK. A novel thrombomodulin gene mutation in a patient suffering from sagittal sinus thrombosis. Thromb Haemost 1997; 78: 1164-6. 110 Kunz G, Ireland HA, Stubbs PJ, Kahan M, Coulton GC, Lane DA. Identification and characterization of a thrombomodulin gene mutation coding for an elongated protein with reduced expression in a kindred with myocardial infarction. Blood 2000; 95: 569-76. 111 Christie PD, Edelberg JM, Picard MH, Foulkes AS, Mamuya W, Weiler-Guettler H, Rubin RH, Gilbert P, Rosenberg RD. A murine model of myocardial microvascular thrombosis. J Clin Invest 1999; 104: 533-9. 112 Rosenberg RD, Aird WC. Mechanisms of disease: vascular-bed-specific hemostasis and hypercoagulable states. N Engl J Med 1999; 340: 1555-64. 113 Erlich J, Parry GC, Fearns C, Muller M, Carmeliet P, Luther T, Mackman N. Tissue factor is required for uterine hemostasis and maintenance of the placental labyrinth during gestation. Proc Natl Acad Sci USA 1999; 96: 8138-43. 114 Tsakiris DA, Scudder L, Hodivala-Dilke K, Hynes RO, Coller BS. Hemostasis in the mouse (mus musculus): a review. Thromb Haemost 1999; 81: 177-88. 115 Mackman N. Gene targeting in hemostasis. Tissue factor. Front Biosci 2001; 06: D208-15. 116 Chan JC. Gene targeting in hemostasis. Factor VII. Front Biosci 2001; 06: D98-104. 117 Sun WY, Degen SJ. Gene targeting in hemostasis. Prothrombin. Front Biosci 2001; 06: D222-38. 118 Gailani D. Gene targeting in hemostasis. FXI. Front Biosci 2001; 06: D201-7. 119 Drew AF, Liu H, Davidson JM, Daugherty CC, Degen JL. Wound-healing defects in mice lacking fibrinogen. Blood 2001; 97: 3691-8. 120 Degen JL. Genetic interactions between the coagulation and fibrinolytic system. Thromb Haemost 2001; 86: 130-7. 121 Ariens RAS, Alberio G, Moia M, Mannucci PM. Low levels of heparinreleaseable tissue factor pathway inhibitor in young patients with thrombosis. Thromb Haemost 1999; 81: 203-7. 122 Chan JC. Gene targeting in hemostasis. Tissue factor pathway inhibitor. Front Biosci 2001; 06: D216-21. 123 Bock SC. Antithrombin III and Heparin Cofactor II. In: Thrombosis and Hemostasis Basic Principles and clinical Practice. Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN. eds. Philadelphia: Lippincott Williams and Wilkins; 2001: 321-33.
