The biochemical structure and interaction of the four components of the fibrinolytic enzyme system are described and the mechanisms for regulation and control are discussed.
The potential is defined for enhancement of thrombolysis at various levels by use of a variety of agents some of which have therapeutic potential in the human.
ÅstrupT. Fibrinolysis - An overview. In: DavidsonJFRowanRMSamamaMMDesnoyersPC, eds. Progress in Chemical Fibrinolysis and Thrombosis, vol 3, New York: Raven Press1978: 1–57.
2.
ReichE. Plamsinogen activator: secretion by neoplastic cells and macrophages. In: ReichERifkinDBShawE, eds. Proteases and Biological Control, Cold Spring Harbor Laboratory1975: 333–341.
3.
StricklandS. Studies on the role of plasminogen activator in ovulation and early embryogenesis. In: MagnussonSOttesenMFoltmanBDanøKNeurathH, eds. Regulatory Proteolytic Enzymes and their Inhibitors, Oxford: Pergamon Press1978: 181–185.
4.
Sottrup-JensenLClaeysHZajdelMPetersenTEMagnussonS. The primary structure of human plasminogen: isolation of two lysine-binding fragments and one ‘mini’-plasminogen (M.W. 38,000) by elastase-catalyzed-specific limited proteolysis. In: DavidsonJFRowanRMSamamaMMDesnoyersPC, eds. Progress in Chemical Fibrinolysis and Thrombolysis, vol 3, New York: Raven Press1978: 191–209.
5.
Sottrup-JensenLPetersenTEMagnussonS. In: Atlas of Protein Sequence and Structure, 1978; 5 (suppl. 3): 91.
6.
WimanB. Biochemistry of the plasminogen to plasmin conversion. In: GaffneyPJBalkuv-UlutinS, eds. Fibrinolysis. Current Fundamental and Clinical Aspects, London: Academic Press1978: 47–60.
7.
WallénPWimanB. Characterization of human plasminogen. II. Separation and partial characterization of different molecular forms of human plasminogen. Biochim Biophys Acta1972; 257: 122–134.
8.
MarkusGDe PasqualeJLWisslerFC. Quantitative determination of the binding of epsilon-aminocaproic acid to native plasminogen. J Biol Chem1978; 253: 727–732.
9.
RickliEEOtavskyWI. A new method of isolation and some properties of heavy chain of human plasmin. Eur J Biochem1975; 9: 441–447.
10.
RobbinsKCSummariaLHsiehBShahRJ. The peptide chains of human plasmin. Mechanism of activation of human plasminogen to plasmin. J Biol Chem1967; 242: 2333–2342.
11.
SummariaLArzadonLBernabePRobbinsKC. The activation of plasminogen to plasmin by urokinase in the presence of the plasmin inhibitor trasylol. The preparation of plasmin with the same NH2-terminal heavy (A) chain sequence as the parent zymogen. J Biol Chem1975; 250: 3988–3995.
12.
ViolandBNCastellinoFJ. Mechanism of the urokinase-catalyzed activation of human plasminogen. J Biol Chem1976; 251: 3906–3912.
13.
WimanBWallénP. Activation of human plasminogen by an insoluble derivative of urikinase. Structural changes of plasminogen in the course of activation to plasmin and demonstration of a possible intermediate compound. Eur J Biochem1973; 36: 25–31.
14.
KaplanAPCastellinoFJCollenDWimanBTaylorFB. Molecular mechanisms of fibrinolysis in man. Thrombos Haemostas1978; 39: 263–283.
15.
KluftC. An inventory of plasminogen activators in human plasma. Thrombos Haemostas1978; 38: 134.
16.
HednerUNilssonIM. Acquired anticoagulants against factors XI and XII in patients with severe thrombotic disease. 16th Internat Congr of Haematology, Kyoto, Japan 1976; Abstract no. 8–88: 341.
17.
WallénP. Activation of plasminogen with urokinase and tissue activator. In: PaolettiRSherryS, eds. Thrombosis and Urokinase, London: Academic Press1977: 91–102.
18.
ThorsenS. Human urokinase and porcine tissue plasminogen activator. Thesis, University of Copenhagen, Copenhagen: Laegeforeningens Forlag1977.
19.
RijkenDCWijngaardsGZaal-de JongMWelbergenJ. Purification and partial characterization of plasminogen activator from human uterine tissue. Biochim Biophys Acta1979; 580: 140–153.
20.
BrogdenRNSpeightTMAveryGS. Streptokinase: a review of its clinical pharmacology, mechanism of action and therapeutic uses. Drugs1973; 5: 357–445.
21.
CollenD. Identification and some properties of a new fast-reacting plasmin inhibitor in human plasma. Eur J Biochem1976; 69: 209–216.
22.
MoroiMAokiN. Isolation and characterization of alpha 2-plasmin inhibitor from human plasma. A novel proteinase inhibitor which inhibits activator-induced clot lysis. J Biol Chem1976; 251: 5956–5965.
23.
MüllertzSClemmensenI. The primary inhibitor of plasmin in human plasma. Biochem J1976; 159: 545–553.
24.
BaggeLBjörkISaldeenTWallinR. Purification and characterization of an inhibitor of plasminogen activation from post-traumatic patients. Forensic Sci1976; 7: 83–86.
25.
WimanBCollenD. Purification and characterization of human antiplasmin, the fast-acting plasmin inhibitor in plasma. Eur J Biochem1977; 78: 19–26.
26.
HednerUAbildgaardU. Report on the joint Meeting of the task forces on nomenclature and standards of inhibitors of coagulation and fibrinolysis. Thrombos Haemostas1978; 39: 524–525.
27.
ChristensenUClemmensenI. Kinetic properties of the primary inhibitor of plasmin from human plasma. Biochem J1977; 163: 389–391.
28.
WimanBCollenD. On the kinetics of the reaction between human antiplasmin and plasmin. Eur J Biochem1978; 84: 573–578.
29.
HednerU. Studies on an inhibitor of plasminogen activation. in human serum. Thrombos Diathes haemorrh1973; 30: 414–424.
30.
SteadNKaplanAPRosenbergRD. Inhibition of activated factor XII by antithrombin-heparin cofactor. J Biol Chem1976; 251: 6481–6488.
31.
McConnelDJ. Inhibitors of kallikrein in human plasma. J Clin Invest1972; 51: 1611–1623.
32.
MüllertzS. Mechanism of activation and effect of plasmin in blood. PhD Thesis, Copenhagen: Eijner Munksgaard1956.
33.
GurewichVHydeELipinskiB. The resistance of fibrinogen and soluble fibrin monomer in blood to degradation by a potent plasminogen activator from cadaver limbs. Blood1975; 46: 555–565.
34.
FletcherAPBiedermanOMooreDAlkjaersigNSherryS. Abnormal plasminogen-plasmin system activity (fibrinolysis) in patients with hepatic cirrhosis: its cause and consequences. J Clin Invest1964; 43: 681–695.
35.
TytgatGCollenDDe VrekerRA. Investigations on the fibrinolytic system in liver cirrhosis. Acta Haematol1968; 40: 265–274.
36.
ÅstrupT. Fibrinolysis in the organism. Blood1956; 11: 781–806.
37.
MüllertzS. Plasminogen activator in spontaneously active human blood. Proc Soc Exper Biol Med1953; 82: 291–295.
38.
PandolfiMIsacsonSNilssonIM. Low Fibrinolytic activity in the walls of veins of patients with thrombosis. Acta Med Scand1969; 186: 1–5.
39.
ChakrabartiRFearnleyGRHockingEDDelitheosAClarkeGM. Fibrinolytic activity related to age in survivors of myocardial infarction. Lancet1966; 1: 573–574.
40.
RosingDRRedwoodDRBrakmanPÅstrupT. Impairment of the diurnal fibrinolytic response in man. Effects of aging, type IV hyperlipoproteinemia, and coronary artery disease. Circ Res1973; 32: 752–758.
41.
McNicolGPFletcherAPAlkjaersigNSherryS. Impairment of hemostasis in the urinary tract: the role of urokinase. J Lab Clin Med1961; 58: 34–36.
42.
NilssonLRyboG. Treatment of menorrhagia with an antifibrinolytic agent, tranexamic acid (AMCA). A double-blind investigation. Acta Obstet Gynec Scand1967; 46: 572–580.
43.
NilssonIMKrookHSternbyNHSöderbergESoderströmN. Severe thrombotic disease in a young man with bone marrow and skeletal changes and with a high content of an inhibitor of the fibrinolytic system. Acta Med Scand1961; 169: 323–337.
44.
BrakmanPAlbrechtsenOKÅstrupT. A comparative study of coagulation and fibrinolysis in blood from normal men and women. Brit J Haemat1966; 12: 74–85.
AokiNMoroiMSakataYYoshidaN. Abnormal plasminogen. A hereditary molecular abnormality found in a patient with recurrent thrombosis. J Clin Invest1978; 61: 1186–1195.
47.
CollenDTytgatGNClaeysHPiessensR. Metabolism and distribution of fibrinogen. I. Fibrinogen turnover in physiological conditions in humans. Brit J Haemat1972; 22: 681–700.
48.
CollenD. Plasminogen and prothrombin metabolism in man. Thesis, University of Leuven, Belgium1974.
49.
CashJD. Control mechanisms of activator release. In: DavidsonJFRowanRMSamamaMMDesnoyersPC, eds. Progress in Chemical Fibrinolysis and Thrombolysis, vol 3, New York: Raven Press1978: 65–75.
50.
CashJD. Platelets, fibrinolysis and stress. In: BrinkhousKM, ed. Thrombosis-risk Factors and Diagnostic Approaches, Stuttgart: Schattauer Verlag1972: 93.
51.
MarkwardtFKlockingHP. Studies on the release of plasminogen activator. Thrombos Res1976; 8: 217–223.
HawkeyCMBrittonBJWoodWGPeeleMIrvingMH. Changes in blood catecholamine levels and blood coagulation and fibrinolytic activity in response to graded exercise in man. Br J Haematol1975; 29: 377–384.
54.
Pina-CabralJMRodriguesC. Blood catecholamine levels, factor VIII and fibrinolysis after therapeutic electroshock. Br J Haemat1974; 28: 371–380.
55.
NilssonIM. Effect of drugs on activator synthesis and release. In: DavidsonJFRowanRMSamamaMMDesnoyersPC, eds. Progress in Chemical Fibrinolysis and Thrombolysis, vol 3, New York: Raven Press1978: 77–89.
56.
DavidsonJFLochheadMMcDonaldGAMcNicolGP. Fibrinolytic enhancement by stanazolol: a double blind trial. Br J Haematol1972; 22: 543–559.
57.
NilssonIM. Phenformin and ethylestrenol in recurrent venous thrombosis. In: DavidsonJFSamamaMMDesnoyersPC, eds. Progress in Chemical Fibrinolysis and Thrombolysis, vol 1, New York: Raven Press1979: 1–12.
58.
ThorsenS. Differences in the binding to fibrin of native plasminogen and plasminogen modified by proteolytic degradation. Influence of omega-amino-carboxylic acids. Biochim Biophys Acta1975; 393: 55–65.
59.
RakocziIWimanBCollenD. On the biological significance of the specific interaction between fibrin, plasminogen and antiplasmin. Biochim Biophys Acta1978; 540: 295–300.
60.
WimanBWallénP. Structural relationship between ‘glutamic acid’ and ‘lysine’ forms of human plasminogen and their interaction with the NH2-terminal activation peptide as studied by affinity chromatography. Eur J Biochem1975; 50: 489–494.
61.
WimanBCollenD. On the role of α2-antiplasmin in the regulation of fibrinolysis. In: CollenDWimanBVerstraeteM, eds. The Physiological Inhibitors of Coagulation and Fibrinolysis, Elsevier/North-Holland1979: 177–185.
62.
CollenDVerstraeteM. α2-Antiplasmin consumption and fibrinogen breakdown during thrombolytic therapy. Thrombos Res1979; 14: 631–639.
63.
CamiloSMThorsenSÅstrupT. Fibrinogenolysis and fibrinolysis with tissue plasminogen activator, urokinase, streptokinase-activated human globulin, and plasmin. Proc Soc Exper Biol Med1971; 138: 277–280.
64.
WimanBCollenD. Molecular mechanism of physiological fibrinolysis. Nature1978; 272: 549–550.
65.
FearnleyGRChakrabartiRVincentCT. Effect of the sulphonylureas on fibrinolysis. Lancet1960; 2: 622–624.
66.
HockingEDChakrabartiREvansJ. Effect of diguanides and atromid on fibrinolysis. Atheroscler Res1967; 7: 121–130.
VerstraeteM. A far-reaching program: rapid, safe, and predictable thrombolysis in man. In: KlineDLReddyNN, eds. Fibrinolysis, CRC Press Inc, in press.
69.
CoccheriSDeRosaVCavallaroniK. Activation of fibrinolysis by means of sulfated polysaccharides: Present status and perspectives. In: DavidsonJFRowanRMSamamaMMDesnoyersPC, eds. Progress in Chemical Fibrinolysis and Thrombolysis, vol 3, New York: Raven Press1978: 461–75.
70.
KakkarVVSagarSLewisM. Treatment of deep-vein thrombosis with intermittent streptokinase and plasminogen infusion. Lancet1975; 2: 674–676.
71.
BrochierMPlaniolTGriguerPRaynaudPhFauchierJPCharbonnierBLatourFPelloisA. Intérêt du traitement séquentiel lysylplasminogène-urokinase et thérapeutique thrombolytique. Coeur Med Interne1977; 16: 513–521.
72.
MarbetGAWalterMSixPNymanDRüstOBilandLDuckertFMadarGDa SilvaAWidmerLKSchmittHEVokalJ. Vergleich verschiedener fibrinolytischer Methoden zur Behandlung venöser Thrombosen. In: NeuhausKDuckertF, eds. Blutgerinnung und Antikoagulation, Stuttgart: Schattauer Verlag1977: 87.
73.
LatalloZSLopaciukSMeissnerJ. A combined treatment with Defibrase and streptokinase. Akt Probl Angiol1975; 26: 181–190.
74.
HeimburgerNSchwickHG. Possible mechanism for activating the fibrinolytic system by synthetic agents. In: Von KaullaKNDavidsonJF, eds. Synthetic Fibrinolytic Thrombolytic Agents, Springfield, Ill: Charles C Thomas1975: 98.
75.
AokiNVon KaullaKN. Inactivation of human serum plasminogen antiactivator by synthetic fibrinolysis inducers. Thrombos Diathes haemorrh1969; 22: 251–262.
76.
AokiNVon KaullaKN. Human serum plasminogen antiactivator: Its distinction from antiplasmin. Amer J Physiol1971; 220: 1137–1145.
