Download PDF
Semin Thromb Hemost 2009; 35(5): 468-477
DOI: 10.1055/s-0029-1234142
© Thieme Medical Publishers

The Impact of the Fibrinolytic System on the Risk of Venous and Arterial Thrombosis

Mirjam E. Meltzer1 , 2 , Carine J. M Doggen2 , Philip G. de Groot1 , Frits R. Rosendaal2 , 3 , Ton Lisman1 , 4
  • 1Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht
  • 2Department of Clinical Epidemiology, University Medical Center Leiden, Leiden
  • 3Department of Thrombosis and Hemostasis, University Medical Center Leiden, Leiden
  • 4Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Gronigen, The Netherlands
Further Information

Publication History

Publication Date:
08 September 2009 (online)

    Permissions and Reprints

ABSTRACT

In this review we discuss the association of overall hypofibrinolysis and individual fibrinolytic protein levels with venous and arterial thrombosis. Decreased overall fibrinolytic potential and high plasma levels of thrombin-activatable fibrinolysis inhibitor have been consistently associated with risk of venous thrombosis, whereas little evidence exists for a role of plasminogen, α2-antiplasmin, tissue plasminogen activator, and plasminogen activator inhibitor 1. Overall fibrinolytic potential has been associated with arterial thrombosis in young individuals, but studies on the individual components gave conflicting results. These inconsistent results could be a consequence of nonfibrinolytic properties of fibrinolytic proteins, including roles in inflammation, vascular remodeling, atherosclerosis, and the metabolic syndrome. The nonfibrinolytic properties of these proteins may have opposing effects on development of arterial disease as compared with the lytic properties, which may explain opposite results in different studies with slightly different population characteristics. These properties may be more relevant in arterial than in venous thrombosis.

KEYWORDS

Fibrinolysis - arterial thrombosis - venous thrombosis

REFERENCES

  • 1 Rosendaal F R. Clotting and myocardial infarction: a cycle of insights.  J Thromb Haemost. 2003;  1(4) 640-642
    CrossrefPubMedGoogle Scholar
  • 2 Lisman T, de Groot P G, Meijers J CM, Rosendaal F R. Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis.  Blood. 2005;  105(3) 1102-1105
    CrossrefPubMedGoogle Scholar
  • 3 Meltzer M E, Doggen C JM, de Groot P G, Rosendaal F R, Lisman T. Reduced plasma fibrinolytic capacity as a potential risk factor for a first myocardial infarction in young men.  Br J Haematol. 2009;  145(1) 121-127
    CrossrefPubMedGoogle Scholar
  • 4 Meltzer M E, Lisman T, Doggen C JM, de Groot P G, Rosendaal F R. Synergistic effects of hypofibrinolysis and genetic and acquired risk factors on the risk of a first venous thrombosis.  PLoS Med. 2008;  5(5) e97
    CrossrefPubMedGoogle Scholar
  • 5 Lijnen H R. Plasmin and matrix metalloproteinases in vascular remodeling.  Thromb Haemost. 2001;  86(1) 324-333
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Kooistra T, Schrauwen Y, Arts J, Emeis J J. Regulation of endothelial cell t-PA synthesis and release.  Int J Hematol. 1994;  59(4) 233-255
    PubMedGoogle Scholar
  • 7 Hoylaerts M, Rijken D C, Lijnen H R, Collen D. Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin.  J Biol Chem. 1982;  257(6) 2912-2919
    PubMedGoogle Scholar
  • 8 Chmielewska J, Rånby M, Wiman B. Kinetics of the inhibition of plasminogen activators by the plasminogen-activator inhibitor. Evidence for ‘second-site’ interactions.  Biochem J. 1988;  251(2) 327-332
    PubMedGoogle Scholar
  • 9 Chmielewska J, Rånby M, Wiman B. Evidence for a rapid inhibitor to tissue plasminogen activator in plasma.  Thromb Res. 1983;  31 427-436
    CrossrefPubMedGoogle Scholar
  • 10 Rijken D C, Lijnen H R. New insights into the molecular mechanisms of the fibrinolytic system.  J Thromb Haemost. 2009;  7(1) 4-13
    CrossrefPubMedGoogle Scholar
  • 11 Collen D. Identification and some properties of a new fast-reacting plasmin inhibitor in human plasma.  Eur J Biochem. 1976;  69(1) 209-216
    CrossrefPubMedGoogle Scholar
  • 12 Rákóczi I, Wiman B, Collen D. On the biological significance of the specific interaction between fibrin, plasminogen and antiplasmin.  Biochim Biophys Acta. 1978;  540(2) 295-300
    PubMedGoogle Scholar
  • 13 Sakata Y, Aoki N. Significance of cross-linking of alpha 2-plasmin inhibitor to fibrin in inhibition of fibrinolysis and in hemostasis.  J Clin Invest. 1982;  69(3) 536-542
    CrossrefPubMedGoogle Scholar
  • 14 Mosnier L O, Bouma B N. Regulation of fibrinolysis by thrombin activatable fibrinolysis inhibitor, an unstable carboxypeptidase B that unites the pathways of coagulation and fibrinolysis.  Arterioscler Thromb Vasc Biol. 2006;  26(11) 2445-2453
    CrossrefPubMedGoogle Scholar
  • 15 Prins M H, Hirsh J. A critical review of the evidence supporting a relationship between impaired fibrinolytic activity and venous thromboembolism.  Arch Intern Med. 1991;  151(9) 1721-1731
    CrossrefPubMedGoogle Scholar
  • 16 Lisman T, Leebeek F WG, Mosnier L O et al.. Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis.  Gastroenterology. 2001;  121(1) 131-139
    CrossrefPubMedGoogle Scholar
  • 17 Guimaräes A H, de Bruijne E L, Lisman T et al.. Hypofibrinolysis as risk factor for arterial thrombosis at young age.  Br J Haematol. 2009;  145(1) 115-120
    CrossrefPubMedGoogle Scholar
  • 18 Meade T W, Ruddock V, Stirling Y, Chakrabarti R, Miller G J. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study.  Lancet. 1993;  342(8879) 1076-1079
    CrossrefPubMedGoogle Scholar
  • 19 Meade T W, Cooper J A, Chakrabarti R, Miller G J, Stirling Y, Howarth D J. Fibrinolytic activity and clotting factors in ischaemic heart disease in women.  BMJ. 1996;  312(7046) 1581
    PubMedGoogle Scholar
  • 20 Zorio E, Castelló R, Falcó C et al.. Thrombin-activatable fibrinolysis inhibitor in young patients with myocardial infarction and its relationship with the fibrinolytic function and the protein C system.  Br J Haematol. 2003;  122(6) 958-965
    CrossrefPubMedGoogle Scholar
  • 21 Juhan-Vague I, Pyke S D, Alessi M C, Jespersen J, Haverkate F, Thompson S G. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities.  Circulation. 1996;  94(9) 2057-2063
    CrossrefPubMedGoogle Scholar
  • 22 Cortellaro M, Cofrancesco E, Boschetti C The PLAT Group et al. Increased fibrin turnover and high PAI-1 activity as predictors of ischemic events in atherosclerotic patients. A case-control study.  Arterioscler Thromb. 1993;  13(10) 1412-1417
    PubMedGoogle Scholar
  • 23 Doggen C JM, Rosendaal F R, Meijers J CM. Levels of intrinsic coagulation factors and the risk of myocardial infarction among men: opposite and synergistic effects of factors XI and XII.  Blood. 2006;  108(13) 4045-4051
    CrossrefPubMedGoogle Scholar
  • 24 Segev A, Ellis M H, Segev F et al.. High prevalence of thrombophilia among young patients with myocardial infarction and few conventional risk factors.  Int J Cardiol. 2005;  98(3) 421-424
    CrossrefPubMedGoogle Scholar
  • 25 Mignatti P, Robbins E, Rifkin D B. Tumor invasion through the human amniotic membrane: requirement for a proteinase cascade.  Cell. 1986;  47(4) 487-498
    CrossrefPubMedGoogle Scholar
  • 26 Lijnen H R. Matrix metalloproteinases and cellular fibrinolytic activity.  Biochemistry (Mosc). 2002;  67(1) 92-98
    PubMedGoogle Scholar
  • 27 Shah P K, Galis Z S. Matrix metalloproteinase hypothesis of plaque rupture: players keep piling up but questions remain.  Circulation. 2001;  104(16) 1878-1880
    PubMedGoogle Scholar
  • 28 Carmeliet P, Moons L, Ploplis V, Plow E, Collen D. Impaired arterial neointima formation in mice with disruption of the plasminogen gene.  J Clin Invest. 1997;  99(2) 200-208
    CrossrefPubMedGoogle Scholar
  • 29 Xiao Q, Danton M J, Witte D P et al.. Plasminogen deficiency accelerates vessel wall disease in mice predisposed to atherosclerosis.  Proc Natl Acad Sci U S A. 1997;  94(19) 10335-10340
    CrossrefPubMedGoogle Scholar
  • 30 Matsushima K, Taguchi M, Kovacs E J, Young H A, Oppenheim J J. Intracellular localization of human monocyte associated interleukin 1 (IL 1) activity and release of biologically active IL 1 from monocytes by trypsin and plasmin.  J Immunol. 1986;  136(8) 2883-2891
    PubMedGoogle Scholar
  • 31 Lyons R M, Gentry L E, Purchio A F, Moses H L. Mechanism of activation of latent recombinant transforming growth factor beta 1 by plasmin.  J Cell Biol. 1990;  110(4) 1361-1367
    CrossrefPubMedGoogle Scholar
  • 32 Degen J L, Bugge T H, Goguen J D. Fibrin and fibrinolysis in infection and host defense.  J Thromb Haemost. 2007;  5(Suppl 1) 24-31
    CrossrefPubMedGoogle Scholar
  • 33 Epstein S E. The multiple mechanisms by which infection may contribute to atherosclerosis development and course.  Circ Res. 2002;  90(1) 2-4
    PubMedGoogle Scholar
  • 34 Favier R, Aoki N, de Moerloose P. Congenital alpha(2)-plasmin inhibitor deficiencies: a review.  Br J Haematol. 2001;  114(1) 4-10
    CrossrefPubMedGoogle Scholar
  • 35 Brandt J T. Plasminogen and tissue-type plasminogen activator deficiency as risk factors for thromboembolic disease.  Arch Pathol Lab Med. 2002;  126(11) 1376-1381
    PubMedGoogle Scholar
  • 36 Okamoto A, Sakata T, Mannami T et al.. Population-based distribution of plasminogen activity and estimated prevalence and relevance to thrombotic diseases of plasminogen deficiency in the Japanese: the Suita Study.  J Thromb Haemost. 2003;  1(11) 2397-2403
    CrossrefPubMedGoogle Scholar
  • 37 Hamsten A, Blombäck M, Wiman B et al.. Haemostatic function in myocardial infarction.  Br Heart J. 1986;  55(1) 58-66
    CrossrefPubMedGoogle Scholar
  • 38 Folsom A R, Aleksic N, Park E, Salomaa V, Juneja H, Wu K K. Prospective study of fibrinolytic factors and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study.  Arterioscler Thromb Vasc Biol. 2001;  21(4) 611-617
    CrossrefPubMedGoogle Scholar
  • 39 Jenkins G R, Seiffert D, Parmer R J, Miles L A. Regulation of plasminogen gene expression by interleukin-6.  Blood. 1997;  89(7) 2394-2403
    PubMedGoogle Scholar
  • 40 Alessi M C, Poggi M, Juhan-Vague I. Plasminogen activator inhibitor-1, adipose tissue and insulin resistance.  Curr Opin Lipidol. 2007;  18(3) 240-245
    CrossrefPubMedGoogle Scholar
  • 41 Samad F, Pandey M, Bell P A, Loskutoff D J. Insulin continues to induce plasminogen activator inhibitor 1 gene expression in insulin-resistant mice and adipocytes.  Mol Med. 2000;  6(8) 680-692
    PubMedGoogle Scholar
  • 42 Peraldi P, Spiegelman B M. Studies of the mechanism of inhibition of insulin signaling by tumor necrosis factor-alpha.  J Endocrinol. 1997;  155(2) 219-220
    CrossrefPubMedGoogle Scholar
  • 43 Samad F, Yamamoto K, Loskutoff D J. Distribution and regulation of plasminogen activator inhibitor-1 in murine adipose tissue in vivo. Induction by tumor necrosis factor-alpha and lipopolysaccharide.  J Clin Invest. 1996;  97(1) 37-46
    CrossrefPubMedGoogle Scholar
  • 44 Sakamoto T, Woodcock-Mitchell J, Marutsuka K, Mitchell J J, Sobel B E, Fujii S. TNF-alpha and insulin, alone and synergistically, induce plasminogen activator inhibitor-1 expression in adipocytes.  Am J Physiol. 1999;  276(6 Pt 1) C1391-C1397
    PubMedGoogle Scholar
  • 45 Festa A, D’Agostino Jr R, Tracy R P, Haffner S M. Insulin Resistance Atherosclerosis Study . Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study.  Diabetes. 2002;  51(4) 1131-1137
    CrossrefPubMedGoogle Scholar
  • 46 Morange P E, Alessi M C, Verdier M, Casanova D, Magalon G, Juhan-Vague I. PAI-1 produced ex vivo by human adipose tissue is relevant to PAI-1 blood level.  Arterioscler Thromb Vasc Biol. 1999;  19(5) 1361-1365
    PubMedGoogle Scholar
  • 47 De Taeye B M, Novitskaya T, Gleaves L, Covington J W, Vaughan D E. Bone marrow plasminogen activator inhibitor-1 influences the development of obesity.  J Biol Chem. 2006;  281(43) 32796-32805
    CrossrefPubMedGoogle Scholar
  • 48 Schäfer K, Fujisawa K, Konstantinides S, Loskutoff D J. Disruption of the plasminogen activator inhibitor 1 gene reduces the adiposity and improves the metabolic profile of genetically obese and diabetic ob/ob mice.  FASEB J. 2001;  15(10) 1840-1842
    PubMedGoogle Scholar
  • 49 Skurk T, Lee Y M, Hauner H. Angiotensin II and its metabolites stimulate PAI-1 protein release from human adipocytes in primary culture.  Hypertension. 2001;  37(5) 1336-1340
    CrossrefPubMedGoogle Scholar
  • 50 Birgel M, Gottschling-Zeller H, Röhrig K, Hauner H. Role of cytokines in the regulation of plasminogen activator inhibitor-1 expression and secretion in newly differentiated subcutaneous human adipocytes.  Arterioscler Thromb Vasc Biol. 2000;  20(6) 1682-1687
    PubMedGoogle Scholar
  • 51 Felmeden D C, Lip G Y. The renin-angiotensin-aldosterone system and fibrinolysis.  J Renin Angiotensin Aldosterone Syst. 2000;  1(3) 240-244
    CrossrefPubMedGoogle Scholar
  • 52 Schneiderman J, Sawdey M S, Keeton M R et al.. Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries.  Proc Natl Acad Sci U S A. 1992;  89(15) 6998-7002
    CrossrefPubMedGoogle Scholar
  • 53 Lupu F, Bergonzelli G E, Heim D A et al.. Localization and production of plasminogen activator inhibitor-1 in human healthy and atherosclerotic arteries.  Arterioscler Thromb. 1993;  13(7) 1090-1100
    CrossrefPubMedGoogle Scholar
  • 54 Sjöland H, Eitzman D T, Gordon D, Westrick R, Nabel E G, Ginsburg D. Atherosclerosis progression in LDL receptor-deficient and apolipoprotein E-deficient mice is independent of genetic alterations in plasminogen activator inhibitor-1.  Arterioscler Thromb Vasc Biol. 2000;  20(3) 846-852
    PubMedGoogle Scholar
  • 55 Eitzman D T, Westrick R J, Xu Z, Tyson J, Ginsburg D. Plasminogen activator inhibitor-1 deficiency protects against atherosclerosis progression in the mouse carotid artery.  Blood. 2000;  96(13) 4212-4215
    PubMedGoogle Scholar
  • 56 Luttun A, Lupu F, Storkebaum E et al.. Lack of plasminogen activator inhibitor-1 promotes growth and abnormal matrix remodeling of advanced atherosclerotic plaques in apolipoprotein E-deficient mice.  Arterioscler Thromb Vasc Biol. 2002;  22(3) 499-505
    CrossrefPubMedGoogle Scholar
  • 57 Kienast J, Padró T, Steins M et al.. Relation of urokinase-type plasminogen activator expression to presence and severity of atherosclerotic lesions in human coronary arteries.  Thromb Haemost. 1998;  79(3) 579-586
    PubMedGoogle Scholar
  • 58 Degryse B, Sier C F, Resnati M, Conese M, Blasi F. PAI-1 inhibits urokinase-induced chemotaxis by internalizing the urokinase receptor.  FEBS Lett. 2001;  505(2) 249-254
    CrossrefPubMedGoogle Scholar
  • 59 Meltzer M E, Doggen C JM, de Groot P G, Rosendaal F R, Lisman T. Fibrinolysis and the risk of venous and arterial thrombosis.  Curr Opin Hematol. 2007;  14(3) 242-248
    CrossrefPubMedGoogle Scholar
  • 60 Grimaudo V, Hauert J, Bachmann F, Kruithof E K. Diurnal variation of the fibrinolytic system.  Thromb Haemost. 1988;  59(3) 495-499
    PubMedGoogle Scholar
  • 61 Mannucci P M, Bernardinelli L, Foco L et al.. Tissue plasminogen activator antigen is strongly associated with myocardial infarction in young women.  J Thromb Haemost. 2005;  3(2) 280-286
    CrossrefPubMedGoogle Scholar
  • 62 Thögersen A M, Jansson J H, Boman K et al.. High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor.  Circulation. 1998;  98(21) 2241-2247
    CrossrefPubMedGoogle Scholar
  • 63 Scarabin P Y, Aillaud M F, Amouyel P Prospective Epidemiological Study of Myocardial Infarction et al. Associations of fibrinogen, factor VII and PAI-1 with baseline findings among 10,500 male participants in a prospective study of myocardial infarction—the PRIME Study.  Thromb Haemost. 1998;  80(5) 749-756
    PubMedGoogle Scholar
  • 64 Lundblad D, Dinesen B, Rautio A, Røder M E, Eliasson M. Low level of tissue plasminogen activator activity in non-diabetic patients with a first myocardial infarction.  J Intern Med. 2005;  258(1) 13-20
    CrossrefPubMedGoogle Scholar
  • 65 Smith A, Patterson C, Yarnell J, Rumley A, Ben-Shlomo Y, Lowe G. Which hemostatic markers add to the predictive value of conventional risk factors for coronary heart disease and ischemic stroke? The Caerphilly Study.  Circulation. 2005;  112(20) 3080-3087
    CrossrefPubMedGoogle Scholar
  • 66 Verheugt F W, ten Cate J W, Sturk A et al.. Tissue plasminogen activator activity and inhibition in acute myocardial infarction and angiographically normal coronary arteries.  Am J Cardiol. 1987;  59(12) 1075-1079
    CrossrefPubMedGoogle Scholar
  • 67 Båvenholm P, de Faire U, Landou C et al.. Progression of coronary artery disease in young male post-infarction patients is linked to disturbances of carbohydrate and lipoprotein metabolism and to impaired fibrinolytic function.  Eur Heart J. 1998;  19(3) 402-410
    CrossrefPubMedGoogle Scholar
  • 68 Juhan-Vague I, Morange P E, Frere C HIFMECH Study Group et al. The plasminogen activator inhibitor-1 -675 4G/5G genotype influences the risk of myocardial infarction associated with elevated plasma proinsulin and insulin concentrations in men from Europe: the HIFMECH study.  J Thromb Haemost. 2003;  1(11) 2322-2329
    CrossrefPubMedGoogle Scholar
  • 69 Munkvad S, Gram J, Jespersen J. A depression of active tissue plasminogen activator in plasma characterizes patients with unstable angina pectoris who develop myocardial infarction.  Eur Heart J. 1990;  11(6) 525-528
    PubMedGoogle Scholar
  • 70 Robinson S D, Ludlam C A, Boon N A, Newby D E. Endothelial fibrinolytic capacity predicts future adverse cardiovascular events in patients with coronary heart disease.  Arterioscler Thromb Vasc Biol. 2007;  27(7) 1651-1656
    CrossrefPubMedGoogle Scholar
  • 71 Jansson J H, Nilsson T K, Olofsson B O. Tissue plasminogen activator and other risk factors as predictors of cardiovascular events in patients with severe angina pectoris.  Eur Heart J. 1991;  12(2) 157-161
    PubMedGoogle Scholar
  • 72 Cushman M, Lemaitre R N, Kuller L H et al.. Fibrinolytic activation markers predict myocardial infarction in the elderly. The Cardiovascular Health Study.  Arterioscler Thromb Vasc Biol. 1999;  19(3) 493-498
    CrossrefPubMedGoogle Scholar
  • 73 Itakura H, Sobel B E, Boothroyd D Atherosclerotic Disease, Vascular Function and Genetic Epidemiology Advance (ADVANCE) Study et al. Do plasma biomarkers of coagulation and fibrinolysis differ between patients who have experienced an acute myocardial infarction versus stable exertional angina?.  Am Heart J. 2007;  154(6) 1059-1064
    CrossrefPubMedGoogle Scholar
  • 74 Ridker P M, Vaughan D E, Stampfer M J et al.. Baseline fibrinolytic state and the risk of future venous thrombosis. A prospective study of endogenous tissue-type plasminogen activator and plasminogen activator inhibitor.  Circulation. 1992;  85(5) 1822-1827
    PubMedGoogle Scholar
  • 75 Ladenvall P, Johansson L, Jansson J H et al.. Tissue-type plasminogen activator -7,351C/T enhancer polymorphism is associated with a first myocardial infarction.  Thromb Haemost. 2002;  87(1) 105-109
    PubMedGoogle Scholar
  • 76 Tzoulaki I, Murray G D, Lee A J, Rumley A, Lowe G D, Fowkes F G. Relative value of inflammatory, hemostatic, and rheological factors for incident myocardial infarction and stroke: the Edinburgh Artery Study.  Circulation. 2007;  115(16) 2119-2127
    CrossrefPubMedGoogle Scholar
  • 77 van der Bom J G, de Knijff P, Haverkate F et al.. Tissue plasminogen activator and risk of myocardial infarction. The Rotterdam Study.  Circulation. 1997;  95(12) 2623-2627
    PubMedGoogle Scholar
  • 78 Lowe G D, Danesh J, Lewington S et al.. Tissue plasminogen activator antigen and coronary heart disease. Prospective study and meta-analysis.  Eur Heart J. 2004;  25(3) 252-259
    CrossrefPubMedGoogle Scholar
  • 79 Gram J, Bladbjerg E M, Møller L, Sjøl A, Jespersen J. Tissue-type plasminogen activator and C-reactive protein in acute coronary heart disease. A nested case-control study.  J Intern Med. 2000;  247(2) 205-212
    CrossrefPubMedGoogle Scholar
  • 80 Pineda J, Marin F, Marco P et al.. Premature coronary artery disease in young (age <45) subjects: Interactions of lipid profile, thrombophilic and haemostatic markers.  Int J Cardiol. 2008 July 12;  , (Epub ahead of print)
    PubMedGoogle Scholar
  • 81 MacCallum P K, Cooper J A, Howarth D J, Meade T W, Miller G J. Sex differences in the determinants of fibrinolytic activity.  Thromb Haemost. 1998;  79(3) 587-590
    PubMedGoogle Scholar
  • 82 Crowther M A, Roberts J, Roberts R et al.. Fibrinolytic variables in patients with recurrent venous thrombosis: a prospective cohort study.  Thromb Haemost. 2001;  85(3) 390-394
    PubMedGoogle Scholar
  • 83 Bajzar L, Manuel R, Nesheim M E. Purification and characterization of TAFI, a thrombin-activatable fibrinolysis inhibitor.  J Biol Chem. 1995;  270(24) 14477-14484
    CrossrefPubMedGoogle Scholar
  • 84 Boffa M B, Koschinsky M L. Curiouser and curiouser: recent advances in measurement of thrombin-activatable fibrinolysis inhibitor (TAFI) and in understanding its molecular genetics, gene regulation, and biological roles.  Clin Biochem. 2007;  40(7) 431-442
    CrossrefPubMedGoogle Scholar
  • 85 Campbell W D, Lazoura E, Okada N, Okada H. Inactivation of C3a and C5a octapeptides by carboxypeptidase R and carboxypeptidase N.  Microbiol Immunol. 2002;  46(2) 131-134
    PubMedGoogle Scholar
  • 86 Myles T, Nishimura T, Yun T H et al.. Thrombin activatable fibrinolysis inhibitor, a potential regulator of vascular inflammation.  J Biol Chem. 2003;  278(51) 51059-51067
    CrossrefPubMedGoogle Scholar
  • 87 Swaisgood C M, Schmitt D, Eaton D, Plow E F. In vivo regulation of plasminogen function by plasma carboxypeptidase B.  J Clin Invest. 2002;  110(9) 1275-1282
    CrossrefPubMedGoogle Scholar
  • 88 Asai S, Sato T, Tada T et al.. Absence of procarboxypeptidase R induces complement-mediated lethal inflammation in lipopolysaccharide-primed mice.  J Immunol. 2004;  173(7) 4669-4674
    PubMedGoogle Scholar
  • 89 Sato T, Miwa T, Akatsu H et al.. Pro-carboxypeptidase R is an acute phase protein in the mouse, whereas carboxypeptidase N is not.  J Immunol. 2000;  165(2) 1053-1058
    PubMedGoogle Scholar
  • 90 te Velde E A, Wagenaar G T, Reijerkerk A et al.. Impaired healing of cutaneous wounds and colonic anastomoses in mice lacking thrombin-activatable fibrinolysis inhibitor.  J Thromb Haemost. 2003;  1(10) 2087-2096
    CrossrefPubMedGoogle Scholar
  • 91 van Tilburg N H, Rosendaal F R, Bertina R M. Thrombin activatable fibrinolysis inhibitor and the risk for deep vein thrombosis.  Blood. 2000;  95(9) 2855-2859
    PubMedGoogle Scholar
  • 92 Eichinger S, Schönauer V, Weltermann A et al.. Thrombin-activatable fibrinolysis inhibitor and the risk for recurrent venous thromboembolism.  Blood. 2004;  103(10) 3773-3776
    CrossrefPubMedGoogle Scholar
  • 93 Libourel E J, Bank I, Meinardi J R et al.. Co-segregation of thrombophilic disorders in factor V Leiden carriers; the contributions of factor VIII, factor XI, thrombin activatable fibrinolysis inhibitor and lipoprotein(a) to the absolute risk of venous thromboembolism.  Haematologica. 2002;  87(10) 1068-1073
    PubMedGoogle Scholar
  • 94 Silveira A, Schatteman K, Goossens F et al.. Plasma procarboxypeptidase U in men with symptomatic coronary artery disease.  Thromb Haemost. 2000;  84(3) 364-368
    PubMedGoogle Scholar
  • 95 Santamaría A, Martínez-Rubio A, Borrell M, Mateo J, Ortín R, Fontcuberta J. Risk of acute coronary artery disease associated with functional thrombin activatable fibrinolysis inhibitor plasma level.  Haematologica. 2004;  89(7) 880-881
    PubMedGoogle Scholar
  • 96 Schroeder V, Wilmer M, Buehler B, Kohler H P. TAFI activity in coronary artery disease: a contribution to the current discussion on TAFI assays.  Thromb Haemost. 2006;  96(2) 236-237
    PubMedGoogle Scholar
  • 97 Morange P E, Tregouet D A, Frere C The Prime Study Group et al. TAFI gene haplotypes, TAFI plasma levels and future risk of coronary heart disease: the PRIME Study.  J Thromb Haemost. 2005;  3(7) 1503-1510
    CrossrefPubMedGoogle Scholar
  • 98 Meltzer M E, Doggen C J, de Groot P G, Meijers J C, Rosendaal F R, Lisman T. Low thrombin activatable fibrinolysis inhibitor activity levels are associated with an increased risk of a first myocardial infarction in men.  Haematologica. 2009;  94(6) 811-818
    CrossrefPubMedGoogle Scholar

Ton LismanPh.D. 

Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen

University of Groningen, the Netherlands

Email: J.A.Lisman@chir.umcg.nl