CC BY 4.0 · TH Open 2018; 02(02): e218-e228
DOI: 10.1055/s-0038-1660505
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Effects of Plasmin on von Willebrand Factor and Platelets: A Narrative Review

Lisa N. van der Vorm
1   Synapse Research Institute, Maastricht, The Netherlands
2   Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands
3   Department of Clinical Chemistry and Hematology, Gelre Hospitals, Apeldoorn, The Netherlands
,
Jasper A. Remijn
2   Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands
3   Department of Clinical Chemistry and Hematology, Gelre Hospitals, Apeldoorn, The Netherlands
,
Bas de Laat
1   Synapse Research Institute, Maastricht, The Netherlands
2   Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands
3   Department of Clinical Chemistry and Hematology, Gelre Hospitals, Apeldoorn, The Netherlands
,
Dana Huskens
1   Synapse Research Institute, Maastricht, The Netherlands
2   Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands
› Institutsangaben
Weitere Informationen

Publikationsverlauf

28. Februar 2018

03. Mai 2018

Publikationsdatum:
07. Juni 2018 (online)

Abstract

Plasmin is the major fibrinolytic protease responsible for dissolving thrombi by cleavage of its primary substrate fibrin. In addition, emerging evidence points to other roles of plasmin: (1) as a back-up for ADAMTS13 in proteolysis of ultra-large von Willebrand factor (VWF) multimers and (2) as an activator of platelets. Although the molecular mechanisms of fibrinolysis are well defined, insights on the effects of plasmin on VWF and platelets are relatively scarce and sometimes conflicting. Hence, this review provides an overview of the literature on the effects of plasmin on VWF multimeric structures, on VWF binding to platelets, and on platelet activation. This information is placed in the context of possible applications of thrombolytic therapy for the condition thrombotic thrombocytopenic purpura.

 
  • References

  • 1 Longstaff C, Kolev K. Basic mechanisms and regulation of fibrinolysis. J Thromb Haemost 2015; 13 (Suppl. 01) S98-S105
  • 2 Cesarman-Maus G, Hajjar KA. Molecular mechanisms of fibrinolysis. Br J Haematol 2005; 129 (03) 307-321
  • 3 Brophy TM, Ward SE, McGimsey TR. , et al. Plasmin cleaves von Willebrand factor at K1491-R1492 in the A1-A2 linker region in a shear- and glycan-dependent manner in vitro. Arterioscler Thromb Vasc Biol 2017; 37 (05) 845-855
  • 4 Tersteeg C, de Maat S, De Meyer SF. , et al. Plasmin cleavage of von Willebrand factor as an emergency bypass for ADAMTS13 deficiency in thrombotic microangiopathy. Circulation 2014; 129 (12) 1320-1331
  • 5 Raum D, Marcus D, Alper CA, Levey R, Taylor PD, Starzl TE. Synthesis of human plasminogen by the liver. Science 1980; 208 (4447): 1036-1037
  • 6 Hajjar KA. The molecular basis of fibrinolysis. In: Nathan DG, Orkin SH, Ginsburg D, Look AT. , eds. Hematology of Infancy and Childhood. Philadelphia, PA: WB Saunders Co; 2003: 1497-1514
  • 7 Forsgren M, Råden B, Israelsson M, Larsson K, Hedén LO. Molecular cloning and characterization of a full-length cDNA clone for human plasminogen. FEBS Lett 1987; 213 (02) 254-260
  • 8 Holvoet P, Lijnen HR, Collen D. A monoclonal antibody specific for Lys-plasminogen. Application to the study of the activation pathways of plasminogen in vivo. J Biol Chem 1985; 260 (22) 12106-12111
  • 9 Ny T, Sawdey M, Lawrence D, Millan JL, Loskutoff DJ. Cloning and sequence of a cDNA coding for the human beta-migrating endothelial-cell-type plasminogen activator inhibitor. Proc Natl Acad Sci U S A 1986; 83 (18) 6776-6780
  • 10 Ye RD, Wun TC, Sadler JE. cDNA cloning and expression in Escherichia coli of a plasminogen activator inhibitor from human placenta. J Biol Chem 1987; 262 (08) 3718-3725
  • 11 Thorsen S, Clemmensen I, Sottrup-Jensen L, Magnusson S. Adsorption to fibrin of native fragments of known primary structure from human plasminogen. Biochim Biophys Acta 1981; 668 (03) 377-387
  • 12 Medved L, Nieuwenhuizen W. Molecular mechanisms of initiation of fibrinolysis by fibrin. Thromb Haemost 2003; 89 (03) 409-419
  • 13 Redlitz A, Tan AK, Eaton DL, Plow EF. Plasma carboxypeptidases as regulators of the plasminogen system. J Clin Invest 1995; 96 (05) 2534-2538
  • 14 Aoki N, Moroi M, Tachiya K. Effects of alpha2-plasmin inhibitor on fibrin clot lysis. Its comparison with alpha2-macroglobulin. Thromb Haemost 1978; 39 (01) 22-31
  • 15 Omar MN, Mann KG. Inactivation of factor Va by plasmin. J Biol Chem 1987; 262 (20) 9750-9755
  • 16 Ogiwara K, Nogami K, Nishiya K, Shima M. Plasmin-induced procoagulant effects in the blood coagulation: a crucial role of coagulation factors V and VIII. Blood Coagul Fibrinolysis 2010; 21 (06) 568-576
  • 17 Samis JA, Ramsey GD, Walker JB, Nesheim ME, Giles AR. Proteolytic processing of human coagulation factor IX by plasmin. Blood 2000; 95 (03) 943-951
  • 18 Pryzdial EL, Lavigne N, Dupuis N, Kessler GE. Plasmin converts factor X from coagulation zymogen to fibrinolysis cofactor. J Biol Chem 1999; 274 (13) 8500-8505
  • 19 Li A, Wun TC. Proteolysis of tissue factor pathway inhibitor (TFPI) by plasmin: effect on TFPI activity. Thromb Haemost 1998; 80 (03) 423-427
  • 20 Collen D, Lijnen HR. Basic and clinical aspects of fibrinolysis and thrombolysis. Blood 1991; 78 (12) 3114-3124
  • 21 Crawley JT, Lam JK, Rance JB, Mollica LR, O'Donnell JS, Lane DA. Proteolytic inactivation of ADAMTS13 by thrombin and plasmin. Blood 2005; 105 (03) 1085-1093
  • 22 Peyvandi F, Garagiola I, Baronciani L. Role of von Willebrand factor in the haemostasis. Blood Transfus 2011; 9 (Suppl. 02) s3-s8
  • 23 Wagner DD. Cell biology of von Willebrand factor. Annu Rev Cell Biol 1990; 6: 217-246
  • 24 Furlan M. Von Willebrand factor: molecular size and functional activity. Ann Hematol 1996; 72 (06) 341-348
  • 25 Zhou YF, Eng ET, Zhu J, Lu C, Walz T, Springer TA. Sequence and structure relationships within von Willebrand factor. Blood 2012; 120 (02) 449-458
  • 26 Schneider SW, Nuschele S, Wixforth A. , et al. Shear-induced unfolding triggers adhesion of von Willebrand factor fibers. Proc Natl Acad Sci U S A 2007; 104 (19) 7899-7903
  • 27 Ruggeri ZM. Role of von Willebrand factor in platelet thrombus formation. Ann Med 2000; 32 (Suppl. 01) 2-9
  • 28 Owen WG, Wagner RH. Antihemophilic factor: separation of an active fragment following dissociation by salts or detergents. Thromb Diath Haemorrh 1972; 27 (03) 502-515
  • 29 Dong JF, Moake JL, Nolasco L. , et al. ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions. Blood 2002; 100 (12) 4033-4039
  • 30 Liu L, Choi H, Bernardo A. , et al. Platelet-derived VWF-cleaving metalloprotease ADAMTS-13. J Thromb Haemost 2005; 3 (11) 2536-2544
  • 31 Savage B, Sixma JJ, Ruggeri ZM. Functional self-association of von Willebrand factor during platelet adhesion under flow. Proc Natl Acad Sci U S A 2002; 99 (01) 425-430
  • 32 Savage B, Saldívar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell 1996; 84 (02) 289-297
  • 33 Vicente V, Kostel PJ, Ruggeri ZM. Isolation and functional characterization of the von Willebrand factor-binding domain located between residues His1-Arg293 of the alpha-chain of glycoprotein Ib. J Biol Chem 1988; 263 (34) 18473-18479
  • 34 Fujimura Y, Titani K, Holland LZ. , et al. von Willebrand factor. A reduced and alkylated 52/48-kDa fragment beginning at amino acid residue 449 contains the domain interacting with platelet glycoprotein Ib. J Biol Chem 1986; 261 (01) 381-385
  • 35 Plow EF, Pierschbacher MD, Ruoslahti E, Marguerie GA, Ginsberg MH. The effect of Arg-Gly-Asp-containing peptides on fibrinogen and von Willebrand factor binding to platelets. Proc Natl Acad Sci U S A 1985; 82 (23) 8057-8061
  • 36 Tsai HM, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 1998; 339 (22) 1585-1594
  • 37 van Mourik JA, Boertjes R, Huisveld IA. , et al. von Willebrand factor propeptide in vascular disorders: a tool to distinguish between acute and chronic endothelial cell perturbation. Blood 1999; 94 (01) 179-185
  • 38 Crawley JT, Scully MA. Thrombotic thrombocytopenic purpura: basic pathophysiology and therapeutic strategies. Hematology (Am Soc Hematol Educ Program) 2013; 2013: 292-299
  • 39 Zheng XL, Kaufman RM, Goodnough LT, Sadler JE. Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura. Blood 2004; 103 (11) 4043-4049
  • 40 Furlan M, Robles R, Galbusera M. , et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med 1998; 339 (22) 1578-1584
  • 41 Jin M, Casper TC, Cataland SR. , et al. Relationship between ADAMTS13 activity in clinical remission and the risk of TTP relapse. Br J Haematol 2008; 141 (05) 651-658
  • 42 Peyvandi F, Lavoretano S, Palla R. , et al. ADAMTS13 and anti-ADAMTS13 antibodies as markers for recurrence of acquired thrombotic thrombocytopenic purpura during remission. Haematologica 2008; 93 (02) 232-239
  • 43 Kolev K, Léránt I, Tenekejiev K, Machovich R. Regulation of fibrinolytic activity of neutrophil leukocyte elastase, plasmin, and miniplasmin by plasma protease inhibitors. J Biol Chem 1994; 269 (25) 17030-17034
  • 44 Switzer ME, McKee PA. Immunologic studies of native and modified human factor VIII/von Willebrand factor. Blood 1979; 54 (02) 310-321
  • 45 Hamilton KK, Fretto LJ, Grierson DS, McKee PA. Effects of plasmin on von Willebrand factor multimers. Degradation in vitro and stimulation of release in vivo. J Clin Invest 1985; 76 (01) 261-270
  • 46 Atichartakarn V, Marder VJ, Kirby EP, Budzynski AZ. Effects of enzymatic degradation on the subunit composition and biologic properties of human factor VIII. Blood 1978; 51 (02) 281-297
  • 47 Henriksson P, Nilsson IM. Effects of leukocytes, plasmin and thrombin on clotting factors. A comparative in vitro study. Thromb Res 1979; 16 (3-4): 301-312
  • 48 Bonnefoy A, Legrand C. Proteolysis of subendothelial adhesive glycoproteins (fibronectin, thrombospondin, and von Willebrand factor) by plasmin, leukocyte cathepsin G, and elastase. Thromb Res 2000; 98 (04) 323-332
  • 49 Tanka-Salamon A, Kolev K, Machovich R, Komorowicz E. Proteolytic resistance conferred to fibrinogen by von Willebrand factor. Thromb Haemost 2010; 103 (02) 291-298
  • 50 Wohner N, Kovács A, Machovich R, Kolev K. Modulation of the von Willebrand factor-dependent platelet adhesion through alternative proteolytic pathways. Thromb Res 2012; 129 (04) e41-e46
  • 51 Federici AB, Elder JH, De Marco L, Ruggeri ZM, Zimmerman TS. Carbohydrate moiety of von Willebrand factor is not necessary for maintaining multimeric structure and ristocetin cofactor activity but protects from proteolytic degradation. J Clin Invest 1984; 74 (06) 2049-2055
  • 52 McGrath RT, McKinnon TA, Byrne B. , et al. Expression of terminal alpha2-6-linked sialic acid on von Willebrand factor specifically enhances proteolysis by ADAMTS13. Blood 2010; 115 (13) 2666-2673
  • 53 Berkowitz SD, Federici AB. Sialic acid prevents loss of large von Willebrand factor multimers by protecting against amino-terminal proteolytic cleavage. Blood 1988; 72 (05) 1790-1796
  • 54 McKinnon TA, Chion AC, Millington AJ, Lane DA, Laffan MA. N-linked glycosylation of VWF modulates its interaction with ADAMTS13. Blood 2008; 111 (06) 3042-3049
  • 55 Nowak AA, Canis K, Riddell A, Laffan MA, McKinnon TA. O-linked glycosylation of von Willebrand factor modulates the interaction with platelet receptor glycoprotein Ib under static and shear stress conditions. Blood 2012; 120 (01) 214-222
  • 56 Bowen DJ. An influence of ABO blood group on the rate of proteolysis of von Willebrand factor by ADAMTS13. J Thromb Haemost 2003; 1 (01) 33-40
  • 57 Graham CH, Fitzpatrick TE, McCrae KR. Hypoxia stimulates urokinase receptor expression through a heme protein-dependent pathway. Blood 1998; 91 (09) 3300-3307
  • 58 Broos K, Feys HB, De Meyer SF, Vanhoorelbeke K, Deckmyn H. Platelets at work in primary hemostasis. Blood Rev 2011; 25 (04) 155-167
  • 59 Califf RM, Fortin DF, Tenaglia AN, Sane DC. Clinical risks of thrombolytic therapy. Am J Cardiol 1992; 69 (02) 12A-20A
  • 60 Schweizer J, Kirch W, Koch R. , et al. Short- and long-term results after thrombolytic treatment of deep venous thrombosis. J Am Coll Cardiol 2000; 36 (04) 1336-1343
  • 61 Coller BS. Platelets and thrombolytic therapy. N Engl J Med 1990; 322 (01) 33-42
  • 62 Fitzgerald DJ, Catella F, Roy L, FitzGerald GA. Marked platelet activation in vivo after intravenous streptokinase in patients with acute myocardial infarction. Circulation 1988; 77 (01) 142-150
  • 63 Ohlstein EH, Storer B, Fujita T, Shebuski RJ. Tissue-type plasminogen activator and streptokinase induce platelet hyperaggregability in the rabbit. Thromb Res 1987; 46 (04) 575-585
  • 64 Kerins DM, Roy L, FitzGerald GA, Fitzgerald DJ. Platelet and vascular function during coronary thrombolysis with tissue-type plasminogen activator. Circulation 1989; 80 (06) 1718-1725
  • 65 Fitzgerald DJ, Wright F, FitzGerald GA. Increased thromboxane biosynthesis during coronary thrombolysis. Evidence that platelet activation and thromboxane A2 modulate the response to tissue-type plasminogen activator in vivo. Circ Res 1989; 65 (01) 83-94
  • 66 Watabe A, Ohta M, Matsuyama N. , et al. Characterization of plasmin-induced platelet aggregation. Res Commun Mol Pathol Pharmacol 1997; 96 (03) 341-352
  • 67 Niewiarowski S, Senyi AF, Gillies P. Plasmin-induced platelet aggregation and platelet release reaction. Effects on hemostasis. J Clin Invest 1973; 52 (07) 1647-1659
  • 68 Niewiarowski S, Gurewich V, Senyi AF, Mustard JF. The effect of fibrinolysis on platelet function. Thromb Diath Haemorrh Suppl 1971; 47: 99
  • 69 Miller JL, Katz AJ, Feinstein MB. Plasmin inhibition of thrombin-induced platelet aggregation. Thromb Diath Haemorrh 1975; 33 (02) 286-309
  • 70 Schafer AI, Maas AK, Ware JA, Johnson PC, Rittenhouse SE, Salzman EW. Platelet protein phosphorylation, elevation of cytosolic calcium, and inositol phospholipid breakdown in platelet activation induced by plasmin. J Clin Invest 1986; 78 (01) 73-79
  • 71 Nakamura K, Kimura M, Fenton II JW, Andersen TT, Aviv A. Duality of plasmin effect on cytosolic free calcium in human platelets. Am J Physiol 1995; 268 (4, Pt 1): C958-C967
  • 72 Ishii-Watabe A, Uchida E, Mizuguchi H, Hayakawa T. On the mechanism of plasmin-induced platelet aggregation. Implications of the dual role of granule ADP. Biochem Pharmacol 2000; 59 (11) 1345-1355
  • 73 Pasche B, Loscalzo J. Platelets and fibrinolysis. Platelets 1991; 2 (03) 125-134
  • 74 Loscalzo J, Pasche B, Ouimet H, Freedman JE. Platelets and plasminogen activation. Thromb Haemost 1995; 74 (01) 291-293
  • 75 Friberger P. Synthetic peptide substrate assays in coagulation and fibrinolysis and their application on automates. Semin Thromb Hemost 1983; 9 (04) 281-300
  • 76 Rudd MA, George D, Amarante P, Vaughan DE, Loscalzo J. Temporal effects of thrombolytic agents on platelet function in vivo and their modulation by prostaglandins. Circ Res 1990; 67 (05) 1175-1181
  • 77 Ervin AL, Peerschke EI. Platelet activation by sustained exposure to low-dose plasmin. Blood Coagul Fibrinolysis 2001; 12 (06) 415-425
  • 78 Lu H, Soria C, Cramer EM. , et al. Temperature dependence of plasmin-induced activation or inhibition of human platelets. Blood 1991; 77 (05) 996-1005
  • 79 Schafer AI, Adelman B. Plasmin inhibition of platelet function and of arachidonic acid metabolism. J Clin Invest 1985; 75 (02) 456-461
  • 80 Kinlough-Rathbone RL, Perry DW, Rand ML, Packham MA. Pretreatment of human platelets with plasmin inhibits responses to thrombin, but potentiates responses to low concentrations of aggregating agents, including the thrombin receptor activating peptide, SFLLRN. Thromb Haemost 1997; 77 (04) 741-747
  • 81 Adnot S, Ferry N, Hanoune J, Lacombe ML. Plasmin: a possible physiological modulator of the human platelet adenylate cyclase system. Clin Sci (Lond) 1987; 72 (04) 467-473
  • 82 Gresele P, Kleiman NS, Lopez JA, Page CP. Platelets in Thrombotic and Non-Thrombotic Disorders. 1st ed. Cham, Switzerland: Springer International Publishing; 2017
  • 83 Pasche B, Ouimet H, Francis S, Loscalzo J. Structural changes in platelet glycoprotein IIb/IIIa by plasmin: determinants and functional consequences. Blood 1994; 83 (02) 404-414
  • 84 Gouin I, Lecompte T, Morel MC. , et al. In vitro effect of plasmin on human platelet function in plasma. Inhibition of aggregation caused by fibrinogenolysis. Circulation 1992; 85 (03) 935-941
  • 85 de Haan J, Schönberger J, Haan J, van Oeveren W, Eijgelaar A. Tissue-type plasminogen activator and fibrin monomers synergistically cause platelet dysfunction during retransfusion of shed blood after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1993; 106 (06) 1017-1023
  • 86 Blockmans D, Deckmyn H, Hove LV, Vermylen J. The effect of plasmin on platelet function. Platelets 1996; 7 (03) 139-148
  • 87 Kuliopulos A, Covic L, Seeley SK, Sheridan PJ, Helin J, Costello CE. Plasmin desensitization of the PAR1 thrombin receptor: kinetics, sites of truncation, and implications for thrombolytic therapy. Biochemistry 1999; 38 (14) 4572-4585
  • 88 Quinton TM, Kim S, Derian CK, Jin J, Kunapuli SP. Plasmin-mediated activation of platelets occurs by cleavage of protease-activated receptor 4. J Biol Chem 2004; 279 (18) 18434-18439
  • 89 Kimura M, Andersen TT, Fenton II JW, Bahou WF, Aviv A. Plasmin-platelet interaction involves cleavage of functional thrombin receptor. Am J Physiol 1996; 271 (1, Pt 1): C54-C60
  • 90 Parry MA, Myles T, Tschopp J, Stone SR. Cleavage of the thrombin receptor: identification of potential activators and inactivators. Biochem J 1996; 320 (Pt 1): 335-341
  • 91 Adelman B, Michelson AD, Handin RI, Ault KA. Evaluation of platelet glycoprotein Ib by fluorescence flow cytometry. Blood 1985; 66 (02) 423-427
  • 92 Adelman B, Michelson AD, Loscalzo J, Greenberg J, Handin RI. Plasmin effect on platelet glycoprotein Ib-von Willebrand factor interactions. Blood 1985; 65 (01) 32-40
  • 93 Adelman B, Michelson AD, Greenberg J, Handin RI. Proteolysis of platelet glycoprotein Ib by plasmin is facilitated by plasmin lysine-binding regions. Blood 1986; 68 (06) 1280-1284
  • 94 Kamat SG, Michelson AD, Benoit SE. , et al. Fibrinolysis inhibits shear stress-induced platelet aggregation. Circulation 1995; 92 (06) 1399-1407
  • 95 Cramer EM, Lu H, Caen JP, Soria C, Berndt MC, Tenza D. Differential redistribution of platelet glycoproteins Ib and IIb-IIIa after plasmin stimulation. Blood 1991; 77 (04) 694-699
  • 96 Lu H, Soria C, Soria J. , et al. Reversible translocation of glycoprotein Ib in plasmin-treated platelets: consequences for platelet function. Eur J Clin Invest 1993; 23 (12) 785-793
  • 97 Rabhi-Sabile S, Pidard D. Exposure of human platelets to plasmin results in the expression of irreversibly active fibrinogen receptors. Thromb Haemost 1995; 73 (04) 693-701
  • 98 Peyvandi F, Callewaert F. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med 2016; 374 (25) 2497-2498
  • 99 Callewaert F, Roodt J, Ulrichts H. , et al. Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura. Blood 2012; 120 (17) 3603-3610
  • 100 Schaller J, Gerber SS. The plasmin-antiplasmin system: structural and functional aspects. Cell Mol Life Sci 2011; 68 (05) 785-801
  • 101 Walker JB, Nesheim ME. The molecular weights, mass distribution, chain composition, and structure of soluble fibrin degradation products released from a fibrin clot perfused with plasmin. J Biol Chem 1999; 274 (08) 5201-5212
  • 102 Wiman B. Primary structure of peptides released during activation of human plasminogen by urokinase. Eur J Biochem 1973; 39 (01) 1-9
  • 103 Wiman B, Wallén P. Activation of human plasminogen by an insoluble derivative of urokinase. Structural changes of plasminogen in the course of activation to plasmin and demonstration of a possible intermediate compound. Eur J Biochem 1973; 36 (01) 25-31
  • 104 Violand BN, Castellino FJ. Mechanism of the urokinase-catalyzed activation of human plasminogen. J Biol Chem 1976; 251 (13) 3906-3912
  • 105 Lee CD, Mann KG. Activation/inactivation of human factor V by plasmin. Blood 1989; 73 (01) 185-190
  • 106 Zeibdawi AR, Pryzdial EL. Mechanism of factor Va inactivation by plasmin. Loss of A2 and A3 domains from a Ca2+-dependent complex of fragments bound to phospholipid. J Biol Chem 2001; 276 (23) 19929-19936
  • 107 Pennica D, Holmes WE, Kohr WJ. , et al. Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. Nature 1983; 301 (5897): 214-221
  • 108 Johannessen M, Nielsen F, Petersen LC. Plasmin-catalysed cleavage of single chain tissue-type plasminogen activator in fibrin clots. Fibrinolysis 1989; 3 (04) 215-220
  • 109 Irigoyen JP, Muñoz-Cánoves P, Montero L, Koziczak M, Nagamine Y. The plasminogen activator system: biology and regulation. Cell Mol Life Sci 1999; 56 (1-2): 104-132
  • 110 Marx PF, Dawson PE, Bouma BN, Meijers JC. Plasmin-mediated activation and inactivation of thrombin-activatable fibrinolysis inhibitor. Biochemistry 2002; 41 (21) 6688-6696
  • 111 Nogami K, Shima M, Matsumoto T, Nishiya K, Tanaka I, Yoshioka A. Mechanisms of plasmin-catalyzed inactivation of factor VIII: a crucial role for proteolytic cleavage at Arg336 responsible for plasmin-catalyzed factor VIII inactivation. J Biol Chem 2007; 282 (08) 5287-5295
  • 112 Nishiya K, Nogami K, Okada K. , et al. Determination of a factor VIII-interactive region within plasmin responsible for plasmin-catalysed activation and inactivation of factor VIII(a). Thromb Haemost 2010; 104 (01) 105-117