Narrative Reviews
Vol. 4 No. 3 (2025)
https://doi.org/10.4081/btvb.2025.368

The key to fibrinolysis and thrombolysis

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tissue-type plasminogen activator, fibrinolysis, thrombolysis
Published: 9 September 2025
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Authors

Roger Lijnen
roger.lijnen@kuleuven.be
https://orcid.org/0000-0002-2401-1279
Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium.
Désiré Collen
Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium.
This narrative review was written at the occasion of the "Verstraete Centennial Memorial Lecture" organized on September 15, 2025 at NEUROMED (Pozzilli, Italy) by Giovanni de Gaetano and Maria Benedetta Donati. It represents a historical account of contributions by the Center for Molecular and Vascular Biology (CMVB), KU Leuven, Belgium, founded by Marc Verstraete, to our understanding of the regulation of fibrinolysis and the development of thrombolytic therapy. This review covers the long trajectory of events which, over almost half a century, have led from basic biochemical discoveries to the development of recombinant tissue-type plasminogen activator (rt-PA) and other clinically valuable drugs to treat thrombotic diseases.

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Crossref
Scopus
Google Scholar
Europe PMC
Verstraete M, Clark PA, Wright IS. Use of different tissue thromboplastins in the control of anticoagulant therapy. Circulation 1957;6: 213–26. DOI: https://doi.org/10.1161/01.CIR.16.2.213
Committee CS. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996; 348:1329–39. DOI: https://doi.org/10.1016/S0140-6736(96)09457-3
Collen D, Vermylen J. Metabolism of iodine-labeled plasminogen during streptokinase and reptilase therapy in man. Thromb Res 1973;2:239–49. DOI: https://doi.org/10.1016/0049-3848(73)90087-X
Wiman B, Collen D. Purification and characterization of human antiplasmin, the fast-acting plasmin inhibitor in plasma. Eur J Biochem 1977;78: 19–26. DOI: https://doi.org/10.1111/j.1432-1033.1977.tb11709.x
Collen D, Wiman B. Fast-acting plasmin inhibitor in human plasma. Blood 1978;51: 563–9. DOI: https://doi.org/10.1182/blood.V51.4.563.bloodjournal514563
Rijken DC, Lijnen HR. New insights into the molecular mechanisms of the fibrinolytic system. J Thromb Haemost 2009;7:4–13. DOI: https://doi.org/10.1111/j.1538-7836.2008.03220.x
Holmes WE, Nelles L, Lijnen HR, Collen D. Primary structure of human alpha 2-antiplasmin, a serine protease inhibitor (serpin). J Biol Chem 1987;262:1659–64. DOI: https://doi.org/10.1016/S0021-9258(19)75687-7
Lijnen HR, Holmes WE, Van Hoef B, at al. Amino-acid sequence of human alpha 2-antiplasmin. Eur J Biochem 1987;166:565–74. DOI: https://doi.org/10.1111/j.1432-1033.1987.tb13551.x
Wiman B, Collen D. On the mechanism of the reaction between human alpha 2-antiplasmin and plasmin. J Biol Chem 1979;254:9291–7. DOI: https://doi.org/10.1016/S0021-9258(19)86843-6
Wiman B, Lijnen HR, Collen D. On the specific interaction between the lysine-binding sites in plasmin and complementary sites in alpha2-antiplasmin and in fibrinogen. Biochim Biophys Acta 1979;579:142–54. DOI: https://doi.org/10.1016/0005-2795(79)90094-1
Rakoczi I, Wiman B, Collen D. On the biological significance of the specific interaction between fibrin, plasminogen and antiplasmin. Biochim Biophys Acta 1978;540:295–300. DOI: https://doi.org/10.1016/0304-4165(78)90142-3
Holmes WE, Lijnen HR, Nelles L, et al. Alpha 2-antiplasmin Enschede: alanine insertion and abolition of plasmin inhibitory activity. Science 1987;238:209–11. DOI: https://doi.org/10.1126/science.2958938
Astrup T, Permin PM. Fibrinolysis in the animal organism. Nature 1947;159: 81. DOI: https://doi.org/10.1038/159681b0
Collen D, Lijnen HR. The tissue-type plasminogen activator story. Arterioscler Thromb Vasc Biol 2009;29:1151–5. DOI: https://doi.org/10.1161/ATVBAHA.108.179655
Rijken DC, Wijngaards G, Zaal-de Jong M, Welbergen J. Purification and partial characterization of plasminogen activator from human uterine tissue. Biochim Biophys Acta 1979;580:140–53. DOI: https://doi.org/10.1016/0005-2795(79)90205-8
Rijken DC, Collen D. Purification and characterization of the plasminogen activator secreted by human melanoma cells in culture. J Biol Chem 1981;256:7035–41. DOI: https://doi.org/10.1016/S0021-9258(19)69095-2
Pennica D, Holmes WE, Kohr WJ, et al. Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. Nature 1983;301:214–21. DOI: https://doi.org/10.1038/301214a0
Rijken DC, Hoylaerts M, Collen D. Fibrinolytic properties of one-chain and two-chain human extrinsic (tissue-type) plasminogen activator. J Biol Chem 1982;257:2920–5. DOI: https://doi.org/10.1016/S0021-9258(19)81052-9
Lijnen HR, Collen D. Strategies for the improvement of thrombolytic agents. Thromb Haemost 1991;66:88–110. DOI: https://doi.org/10.1055/s-0038-1646377
Kohnert U, Rudolph R, Verheijen JH, et al. Biochemical properties of the kringle 2 and protease domains are maintained in the refolded t-PA deletion variant BM 06.022. Protein Eng 1992;5:93–100. DOI: https://doi.org/10.1093/protein/5.1.93
Paoni NF, Keyt BA, Refino CJ, et al. A slow clearing, fibrin-specific, PAI-1 resistant variant of t-PA (T103N, KHRR 296-299 AAAA). Thromb Haemost 1993;70:307–12. DOI: https://doi.org/10.1055/s-0038-1649571
Hoylaerts M, Rijken DC, Lijnen HR, Collen D. Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin. J Biol Chem 1982;257:2912–9. DOI: https://doi.org/10.1016/S0021-9258(19)81051-7
Hoylaerts M, Lijnen HR, Collen D. Studies on the mechanism of the antifibrinolytic action of tranexamic acid. Biochim Biophys Acta 1981 673:75–85. DOI: https://doi.org/10.1016/0304-4165(81)90312-3
Collen D. On the regulation and control of fibrinolysis. Edward Kowalski Memorial Lecture. Thromb Haemost 1980;43:77–89. DOI: https://doi.org/10.1055/s-0038-1650023
Juhan-Vague I, Moerman B, De Cock F, at al. Plasma levels of a specific inhibitor of tissue-type plasminogen activator (and urokinase) in normal and pathological conditions. Thromb Res 1984;33:523–30. DOI: https://doi.org/10.1016/0049-3848(84)90018-5
Declerck PJ, De Mol M, Alessi MC, et al. Purification and characterization of a plasminogen activator inhibitor 1 binding protein from human plasma. Identification as a multimeric form of S protein (vitronectin). J Biol Chem 1988;263:15454–61. DOI: https://doi.org/10.1016/S0021-9258(19)37610-0
Declerck PJ, De Mol M, Vaughan DE, Collen D. Identification of a conformationally distinct form of plasminogen activator inhibitor-1, acting as a noninhibitory substrate for tissue-type plasminogen activator. J Biol Chem 1992;267:11693–6. DOI: https://doi.org/10.1016/S0021-9258(19)49751-2
Alessi MC, Declerck PJ, De Mol M, at al. Purification and characterization of natural and recombinant human plasminogen activator inhibitor-1 (PAI-1). Eur J Biochem 1988;175:531–40. DOI: https://doi.org/10.1111/j.1432-1033.1988.tb14225.x
Vaughan DE, Declerck PJ, Van Houtte E, at al. Reactivated recombinant plasminogen activator inhibitor-1 (rPAI-1) effectively prevents thrombolysis in vivo. Thromb Haemost 1992;68:60–3. DOI: https://doi.org/10.1055/s-0038-1656318
Ploplis VA, Carmeliet P, Vazirzadeh S, et al. Effects of disruption of the plasminogen gene on thrombosis, growth, and health in mice. Circulation 1995;92:2585–93. DOI: https://doi.org/10.1161/01.CIR.92.9.2585
Lijnen HR, Carmeliet P, Bouche A, et al. Restoration of thrombolytic potential in plasminogen-deficient mice by bolus administration of plasminogen. Blood 1996;88:870–6. DOI: https://doi.org/10.1182/blood.V88.3.870.bloodjournal883870
Carmeliet P, Schoonjans L, Kieckens L, et al. Physiological consequences of loss of plasminogen activator gene function in mice. Nature 1994;368:419–24. DOI: https://doi.org/10.1038/368419a0
Carmeliet P, Moons L, Herbert JM, et al. Urokinase but not tissue plasminogen activator mediates arterial neointima formation in mice. Circ Res 1997;81:829-39. DOI: https://doi.org/10.1161/01.RES.81.5.829
Lijnen HR, Okada K, Matsuo O, et al. Alpha2-antiplasmin gene-deficiency in mice to associated with enhanced fibrinolytic potential without overt bleeding. Blood 1999;93:2274-81. DOI: https://doi.org/10.1182/blood.V93.7.2274.407a30_2274_2281
Carmeliet P, Stassen JM, Schoonjans L, et al. Plasminogen activator inhibitor-1 gene-deficient mice. II. Effects on hemostasis, thrombosis, and thrombolysis. J Clin Invest 1993 92:2756–60. DOI: https://doi.org/10.1172/JCI116893
Carmeliet P, Moons L, Lijnen R, et al. Inhibitory role of plasminogen activator inhibitor-1 in arterial wound healing and neointima formation: a gene targeting and gene transfer study in mice. Circulation 1997;96:3180–91. DOI: https://doi.org/10.1161/01.CIR.96.9.3180
Dewerchin M, Nuffelen AV, Wallays G, et al. Generation and characterization of urokinase receptor-deficient mice. J Clin Invest 1996;97:870–8. DOI: https://doi.org/10.1172/JCI118489
Carmeliet P, Collen D. Gene targeting and gene transfer studies of the plasminogen/plasmin system: implications in thrombosis, hemostasis, neointima formation, and atherosclerosis. FASEB J 1995;9:934–8. DOI: https://doi.org/10.1096/fasebj.9.10.7615162
Carmeliet P, Collen D. Gene manipulation and transfer of the plasminogen and coagulation system in mice. Semin Thromb Hemost 1996;22:525–42. DOI: https://doi.org/10.1055/s-2007-999055
Verstraete M, Amery A, Vermylen J. Feasibility of adequate thrombolytic therapy with streptokinase in peripheral arterial occlusions. I. Clinical and arteriographic results. Br Med J 1963;1:1499–504. DOI: https://doi.org/10.1136/bmj.1.5344.1499
European Working P. Streptokinase in recent myocardial infarction: a controlled multicentre trial. European working party. Br Med J 1971;3:325–31. DOI: https://doi.org/10.1136/bmj.3.5770.325
Streptokinase in Acute Myocardial Infarction. N Engl J Med 1979;301:797–802. DOI: https://doi.org/10.1056/NEJM197910113011501
Matsuo O, Rijken DC, Collen D. Thrombolysis by human tissue plasminogen activator and urokinase in rabbits with experimental pulmonary embolus. Nature 1981;291:590–1. DOI: https://doi.org/10.1038/291590a0
Bergmann SR, Fox KA, Ter-Pogossian MM, at al. Clot-selective coronary thrombolysis with tissue-type plasminogen activator. Science 1983;220:1181–3. DOI: https://doi.org/10.1126/science.6602378
Collen D. Human tissue-type plasminogen activator: from the laboratory to the bedside. Circulation 1985;72:18–20. DOI: https://doi.org/10.1161/01.CIR.72.1.18
Weimar W, Stibbe J, van Seyen AJ, at al. Specific lysis of an iliofemoral thrombus by administration of extrinsic (tissue-type) plasminogen activator. Lancet 1981;2:1018–20. DOI: https://doi.org/10.1016/S0140-6736(81)91217-4
Van de Werf F, Ludbrook PA, Bergmann SR, et al. Coronary thrombolysis with tissue-type plasminogen activator in patients with evolving myocardial infarction. N Engl J Med 1984;310:609–13. DOI: https://doi.org/10.1056/NEJM198403083101001
Collen D, Topol EJ, Tiefenbrunn AJ, et al. Coronary thrombolysis with recombinant human tissue-type plasminogen activator: a prospective, randomized, placebo-controlled trial. Circulation 1984;70:1012–7. DOI: https://doi.org/10.1161/01.CIR.70.6.1012
Verstraete M. Trials of the European Working Party on streptokinase and of the European Cooperative Study Group on alteplase in patients with acute myocardial infarction. European Investigators. J Interv Cardiol 1995;8:611–21. DOI: https://doi.org/10.1111/j.1540-8183.1995.tb00910.x
GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329:673–82. DOI: https://doi.org/10.1056/NEJM199309023291001
GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993;329:1615–22. DOI: https://doi.org/10.1056/NEJM199311253292204
Scheldeman L, Sinnaeve P, Albers GW, at al. Acute myocardial infarction and ischaemic stroke: differences and similarities in reperfusion therapies-a review. Eur Heart J 2024;45:2735–47. DOI: https://doi.org/10.1093/eurheartj/ehae371
Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581–7. DOI: https://doi.org/10.1056/NEJM199512143332401
Muir KW, Ford GA, Ford I, et al. Tenecteplase versus alteplase for acute stroke within 4.5 h of onset (ATTEST-2): a randomised, parallel group, open-label trial. Lancet Neurol 2024;23:1087–96. DOI: https://doi.org/10.1016/S1474-4422(24)00377-6
Li S, Gu HQ, Li H, et al. Reteplase versus alteplase for acute ischemic stroke. N Engl J Med 2024;390:2264–73. DOI: https://doi.org/10.1056/NEJMoa2400314
Verstraete M, Miller GA, Bounameaux H, et al. Intravenous and intrapulmonary recombinant tissue-type plasminogen activator in the treatment of acute massive pulmonary embolism. Circulation 1988;77:353–60. DOI: https://doi.org/10.1161/01.CIR.77.2.353
Lewis JH, Kerber CW, Wilson JH. Effects of fibrinolytic agents and heparin on intravascular clot lysis. Am J Physiol 1964;207:1044–8. DOI: https://doi.org/10.1152/ajplegacy.1964.207.5.1044
Collen D, Van Hoef B, Schlott B, et al. Mechanisms of activation of mammalian plasma fibrinolytic systems with streptokinase and with recombinant staphylokinase. Eur J Biochem 1993;216:307–14. DOI: https://doi.org/10.1111/j.1432-1033.1993.tb18147.x
Collen D, Lijnen HR. Staphylokinase, a fibrin-specific plasminogen activator with therapeutic potential? Blood 1994;84:680–6. DOI: https://doi.org/10.1182/blood.V84.3.680.680
Collen D. Staphylokinase: a potent, uniquely fibrin-selective thrombolytic agent. Nat Med 1998;4:279–84. DOI: https://doi.org/10.1038/nm0398-279
Lijnen HR, Van Hoef B, De Cock F, et al. On the mechanism of fibrin-specific plasminogen activation by staphylokinase. J Biol Chem 1991;266:11826–32. DOI: https://doi.org/10.1016/S0021-9258(18)99031-9
Sakharov DV, Lijnen HR, Rijken DC. Interactions between staphylokinase, plasmin(ogen), and fibrin. Staphylokinase discriminates between free plasminogen and plasminogen bound to partially degraded fibrin. J Biol Chem 1996;271:27912–8. DOI: https://doi.org/10.1074/jbc.271.44.27912
Collen D, De Cock F, Stassen JM. Comparative immunogenicity and thrombolytic properties toward arterial and venous thrombi of streptokinase and recombinant staphylokinase in baboons. Circulation 1993;87:996–1006. DOI: https://doi.org/10.1161/01.CIR.87.3.996
Collen D, Van de Werf F. Coronary thrombolysis with recombinant staphylokinase in patients with evolving myocardial infarction. Circulation 1993;87:1850–3. DOI: https://doi.org/10.1161/01.CIR.87.6.1850
Vanderschueren S, Barrios L, Kerdsinchai P, et al. A randomized trial of recombinant staphylokinase versus alteplase for coronary artery patency in acute myocardial infarction. The STAR Trial Group. Circulation 1995;92:2044–9. DOI: https://doi.org/10.1161/01.CIR.92.8.2044
Vanderschueren S, Collen D, van de Werf F. A pilot study on bolus administration of recombinant staphylokinase for coronary artery thrombolysis. Thromb Haemost 1996;76:541–4. DOI: https://doi.org/10.1055/s-0038-1650619
Vanderschueren S, Dens J, Kerdsinchai P, et al. Randomized coronary patency trial of double-bolus recombinant staphylokinase versus front-loaded alteplase in acute myocardial infarction. Am Heart J 1997;134:213–9. DOI: https://doi.org/10.1016/S0002-8703(97)70127-3
Vanderschueren S, Stockx L, Wilms G, et al. Thrombolytic therapy of peripheral arterial occlusion with recombinant staphylokinase. Circulation 1995;92:2050–7. DOI: https://doi.org/10.1161/01.CIR.92.8.2050
Collen D, Stockx L, Lacroix H, at al. Recombinant staphylokinase variants with altered immunoreactivity. IV: Identification of variants with reduced antibody induction but intact potency. Circulation 1997;95:463–72. DOI: https://doi.org/10.1161/01.CIR.95.2.463
Collen D, Sinnaeve P, Demarsin E, et al. Polyethylene glycol-derivatized cysteine-substitution variants of recombinant staphylokinase for single-bolus treatment of acute myocardial infarction. Circulation 2000;102:1766–72. DOI: https://doi.org/10.1161/01.CIR.102.15.1766
Markov VA, Duplyakov DV, Konstantinov SL, et al. Advanced results of Fortelyzin® use in the FRIDOM1 study and real clinical practice. Russian J Cardiol 2022;27:5178. DOI: https://doi.org/10.15829/1560-4071-2022-5178
Gusev EI, Martynov MY, Nikonov AA, et al. Non-immunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4.5 h after symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trial. Lancet Neurol 2021;20:721–8. DOI: https://doi.org/10.1016/S1474-4422(21)00210-6
Kirienko AI, Leontyev SG, Tereschenko SN, et al. Non-immunogenic recombinant staphylokinase versus alteplase for patients with massive pulmonary embolism: a randomized open-label, multicenter, parallel-group, non-inferiority trial, FORPE. J Thromb Haemost 2025;23:657–67. DOI: https://doi.org/10.1016/j.jtha.2024.09.035
Lijnen HR, Stump DC, Collen DC. Single-chain urokinase-type plasminogen activator: mechanism of action and thrombolytic properties. Semin Thromb Hemost 1987;13:152–9. DOI: https://doi.org/10.1055/s-2007-1003486
Lijnen HR, Van Hoef B, Nelles L, Collen D. Plasminogen activation with single-chain urokinase-type plasminogen activator (scu-PA). Studies with active site mutagenized plasminogen (Ser740----Ala) and plasmin-resistant scu-PA (Lys158----Glu). J Biol Chem 1990;265:5232–6. DOI: https://doi.org/10.1016/S0021-9258(19)34111-0
Fleury V, Lijnen HR, Angles-Cano E. Mechanism of the enhanced intrinsic activity of single-chain urokinase-type plasminogen activator during ongoing fibrinolysis. J Biol Chem 1993;268:18554–9. DOI: https://doi.org/10.1016/S0021-9258(17)46663-4
Declerck PJ, Lijnen HR, Verstreken M, at al. A monoclonal antibody specific for two-chain urokinase-type plasminogen activator. Application to the study of the mechanism of clot lysis with single-chain urokinase-type plasminogen activator in plasma. Blood 1990;75:1794–800. DOI: https://doi.org/10.1182/blood.V75.9.1794.bloodjournal7591794
Declerck PJ, Lijnen HR, Verstreken M, Collen D. Role of alpha 2-antiplasmin in fibrin-specific clot lysis with single-chain urokinase-type plasminogen activator in human plasma. Thromb Haemost 1991;65:394–8. DOI: https://doi.org/10.1055/s-0038-1648159
Van de Werf F, Nobuhara M, Collen D. Coronary thrombolysis with human single-chain, urokinase-type plasminogen activator (pro-urokinase) in patients with acute myocardial infarction. Ann Intern Med 1986;104:345–8. DOI: https://doi.org/10.7326/0003-4819-104-3-345
Van de Werf F, Vanhaecke J, de Geest H, at al. Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction. Circulation 1986;74:1066–70. DOI: https://doi.org/10.1161/01.CIR.74.5.1066
Moser M, Bode C. Pharmacology and clinical trial results of saruplase (scuPA) in acute myocardial infarction. Expert Opin Investig Drugs 1999;8:329–35. DOI: https://doi.org/10.1517/13543784.8.3.329
Li S, Gu HQ, Feng B, et al. Safety and efficacy of intravenous recombinant human prourokinase for acute ischaemic stroke within 4.5 h after stroke onset (PROST-2): a phase 3, open-label, non-inferiority, randomised controlled trial. Lancet Neurol 2025;24:33–41. DOI: https://doi.org/10.1016/S1474-4422(24)00436-8
Van de Werf F, Lijnen HR, Collen D. Coronary thrombolysis with K1K2Pu, a chimeric tissue-type and urokinase-type plasminogen activator: a feasibility study in six patients with acute myocardial infarction. Coron Artery Dis 1993;4:929–33. DOI: https://doi.org/10.1097/00019501-199310000-00013
Dewerchin M, Vandamme AM, Holvoet P, et al. Thrombolytic and pharmacokinetic properties of a recombinant chimeric plasminogen activator consisting of a fibrin fragment D-dimer specific humanized monoclonal antibody and a truncated single-chain urokinase. Thromb Haemost 1992;68:170–9. DOI: https://doi.org/10.1055/s-0038-1656344
Holvoet P, Laroche Y, Stassen JM, et al. Pharmacokinetic and thrombolytic properties of chimeric plasminogen activators consisting of a single-chain Fv fragment of a fibrin-specific antibody fused to single-chain urokinase. Blood 1993;81:696–703. DOI: https://doi.org/10.1182/blood.V81.3.696.696
Holvoet P, Laroche Y, Lijnen HR, et al. Characterization of a chimeric plasminogen activator consisting of a single-chain Fv fragment derived from a fibrin fragment D-dimer-specific antibody and a truncated single-chain urokinase. J Biol Chem 1991;266:19717–24. DOI: https://doi.org/10.1016/S0021-9258(18)55051-1
Nagai N, Demarsin E, Van Hoef B, et al. Recombinant human microplasmin: production and potential therapeutic properties. J Thromb Haemost 2003;1:307–13. DOI: https://doi.org/10.1046/j.1538-7836.2003.00078.x
Dommke C, Turschner O, Stassen JM, at al. Thrombolytic efficacy of recombinant human microplasmin in a canine model of copper coil-induced coronary artery thrombosis. J Thromb Thrombolysis 2010;30:46–54. DOI: https://doi.org/10.1007/s11239-009-0400-9
Thijs VN, Peeters A, Vosko M, et al. Randomized, placebo-controlled, dose-ranging clinical trial of intravenous microplasmin in patients with acute ischemic stroke. Stroke 2009;40:3789–95. DOI: https://doi.org/10.1161/STROKEAHA.109.560201
Verhamme P, Heye S, Peerlinck K, et al. Catheter-directed thrombolysis with microplasmin for acute peripheral arterial occlusion (PAO): an exploratory study. Int Angiol 2012;31:289–96.

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Lijnen R, Collen D. The key to fibrinolysis and thrombolysis. Bleeding Thromb Vascul Biol [Internet]. 2025 Sep. 9 [cited 2025 Oct. 7];4(3). Available from: https://www.btvb.org/btvb/article/view/368
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