Biochemie und Physiologie der Blutgerinnung und Fibrinolyse

K. T. Preissner

doi:10.1055/s-0037-1619617

Hämostaseologie, Table of Contents

Hamostaseologie 2004; 24(02): 84-93
DOI: 10.1055/s-0037-1619617

In eigener Sache

Schattauer GmbH

Biochemie und Physiologie der Blutgerinnung und Fibrinolyse

Biochemistry and physiology of blood coagulation and fibrinolysis

K. T. Preissner

Abstract

Zusammenfassung

Die Prinzipien der Auslösemechanismen, Initiator- und Amplifikationsreaktionen der Blutgerinnung und Fibrinolyse werden dargestellt und in Zusammenhang mit Regulationskreisläufen der Hämostase diskutiert. Besonders der Charakter der Zelloberflächen-kontrollierten Aktivierungs- und Inhibierungsreaktionen in Form der Multikomponenten-Enzymkomplexe erlaubt eine endogene physiologische Kontrolle des Systems und ermöglicht im Falle von Störungen der Hämostase eine therapeutische Intervention mit unterschiedlichen pro- und antikoagulatorischen Substanzen.

Summary

The principles of initiator and amplification reactions of blood coagulation and fibrinolysis will be presented and discussed in relation to various regulatory pathways of haemostasis. In particular, cell surface-dependent activation and inhibition reactions are characteristics of multicomponent enzyme complexes that also allow the endogenous physiological control of the haemostasis system. The understanding of these relationships in complications of haemostasis has led to different available strategies for the therapeutic intervention with pro- and anticoagulant substances.

Schlüsselwörter

Multikomponenten-Enzymkomplexe - Thrombin - Feedback-Regulation - Oberflächenreaktionen - Enzymkaskade - Inhibitoren - Gendefekte

Keywords

Multicomponent enzyme complexes - thrombin - feedback regulation - surface reactions - enzyme cascade - inhibitors - gene defects

Full Text

References

Literatur
1 Bertina RM, Koeleman BPC, Koster T. et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
2 Bertina RM. Molecular risk factors for thrombosis. Thromb Haemost 1999; 82: 601-9.
3 Broze GJ, Gailani D. The role of factor XI in coagulation. Thromb Haemost 1993; 70: 72-4.
4 Broze GJ. Protein Z-dependent regulation of coagulation. Thromb Haemost 2001; 86: 8-13.
5 Broze GJ. Tissue factor pathway inhibitor and the revised hypothesis of blood coagulation. Trends Cardio Med 1992; 2: 72-7.
6 Carmeliet P, Mackman N, Moons L. et al. Role of tissue factor in embryonic blood vessel development. Nature 1996; 383: 73-5.
7 Carmeliet P, Collen D. Molecular genetics of the fibrinolytic and coagulation systems in haemostasis, thrombogenesis, restenosis and atherosclerosis. Curr Opin Lipidol 1997; 8: 118-25.
8 Cines DB, Pollak ES, Buck CA. et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998; 91: 3527-61.
9 Coughlin SR. Protease-activated receptors in vascular biology. Thromb Haemost 2001; 86: 298-307.
10 Dahlbäck B. Physiological anticoagulation. Resistance to activated protein C and venous thromboembolism. J Clin Invest 1994; 94: 923-7.
11 Davie EW, Ratnoff OD. Waterfall sequence for intrinsic blood clotting. Science 1964; 145: 1310-2.
12 Degen JL. Hemostatic factors and inflammatory disease. Thromb Haemost 1999; 82: 8858-64.
13 Esmon CT. The protein C pathway: New insights. Thromb Haemost 1997; 78: 70-4.
14 Esmon CT. Thrombomodulin as a model of molecular mechanisms that modulate protease specificity and function at the vessel surface. FASEB J 1995; 9: 946-55.
15 Esmon CT. Role of coagulation inhibitors in inflammation. Thromb Haemost 2001; 86: 51-6.
16 Fukudome K, Esmon CT. Identification, cloning, and regulation of a novel endothelial cell protein C/activated protein C receptor. J Biol Chem 1994; 269: 26486-91.
17 Herz J, Clouthier DE, Hammer RE. LDL receptor-related protein internalizes and degrades uPA-PAI-1 complexes and is essential for embryo implantation. Cell 1992; 71: 411-21.
18 Mann KG. Biochemistry and physiology of blood coagulation. Thromb Haemost 1999; 82: 165-74.
19 Müller-Berghaus G, ten Cate H, Levi M. Disseminated intravascular coagulation: Clinical spectrum and established as well as new diagnostic approaches. Thromb Haemost 1999; 82: 706-12.
20 Nesheim ME, Wang W, Boffa M. et al. Thrombin, thrombomodulin and TAFI in the molecular link between coagulation and fibrinolysis. Thromb Haemost 1997; 78: 386-91.
21 O’Reilly MS, Holmgren L, Shing Y. et al. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994; 79: 315-28.
22 O’Reilly MS, Pirie-Shepherd S, Lane WS. et al. Antiangiogenic activity of the cleaved conformation of the serpin antithrombin. Science 1999; 285: 1926-8.
23 Öhlin AK, Norlund L, Marlar RA. Thrombomodulin gene variations and thromboembolic disease. Thromb Haemost 1997; 78: 392-5.
24 Ossowski L, Clunie G, Masucci MT. et al. In vivo paracrine interaction between urokinase and its receptor: Effect on tumor cell invasion. J Cell Biol 1991; 115: 1107-12.
25 Parkinson JF, Koyama T, Bang NU. et al. Thrombomodulin: an anticoagulant cell surface proteoglycan with physiologically relevant glycosaminoglycan moiety. In: Lane DA, Björk I, Lindahl U. (eds). Heparin and Related Polysaccharides. New York: Plenum Press; 1992: 177-88.
26 Plow EF, Allampallam K, Redlitz A. The plasma carboxypeptidases and the regulation of the plasminogen system. Trends Cardiovas Med 1997; 7: 71-5.
27 Plow EF, Felez J, Miles LA. Cellular regulation of fibrinolysis. Thromb Haemost 1991; 66: 32-6.
28 Preissner KT, Seiffert D. Role of vitronectin and its receptors in haemostasis and vascular remodeling. Thromb Res 1998; 89: 1-21.
29 Preissner KT. Hemostatic protease receptors and entothelial cell function: insights from gene targeting in mice. Semin Thromb Hemost 2000; 5: 451-62.
30 Preissner KT. Physiological role of vessel wall related antithrombotic mechanisms: Contribution of endogenous and exogenous heparin-like components to the anticoagulant potential of the endothelium. Haemostasis 1990; 20: 30-49.
31 Rauch U, Nemerson Y. Circulating tissue factor and thrombosis. Curr Opin Hematol 2000; 7: 273-7.
32 Repke D, Gemmell CH, Guha A. et al. Hemophilia as a defect of the tissue factor pathway of blood coagulation: Effect of factors VIII and IX on factor X activation in a continuous-flow reactor. Proc Natl Acad Sci USA 1990; 87: 7623-7.
33 Rosing J, Tans G, Govers-Riemslag JWP. et al. The role of phospholipids and factor Va in the prothrombinase complex. J Biol Chem 1980; 255: 274-83.
34 Samad F, Loskutoff DJ. The fat mouse: a powerful genetic model to study elevated plasminogen activator inhibitor 1 in obesity/ NIDDM. Thromb Haemost 1997; 78: 652-5.
35 Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Eng J Med 1994; 330: 517-22.
36 Taylor FB, Chang A, Esmon CT. et al. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusions in the baboon. J Clin Invest 1987; 79: 918-25.
37 Zillmann A, Luther T, Muller I. et al. Platelet-associated tissue factor contributes to the collagen-triggered activation of blood coagulation. Biochem Biophys Res Commun 2001; 281: 603-9.
38 Zwaal RFA. Membrane and lipid involvement in blood coagulation. Biochim Biophys Acta 1978; 515: 163-87.