Subscribe to RSS
DOI: 10.1055/s-0038-1646877
Plasminogen Activators and Plasminogen Activator Inhibitors in Liver Deficiencies Caused by Chronic Alcoholism or Infectious Hepatitis
Publication History
Received 21 December 1988
Accepted after revision 17 March 1989
Publication Date:
30 June 2018 (online)
Summary
Plasma concentrations of tissue-type plasminogen activator (t-PA), urokinase (u-PA), plasminogen activator inhibitor 1 (PAI-1) and PAI-2 were studied in 53 patients with liver deficiency caused by chronic alcoholism (n = 40), viral hepatitis (n = 10) or malignant disease of the liver (n = 3) and compared to that of a control group (n = 20) of healthy subjects. u-PA and PAI-1 levels were significantly increased in all patients with chronic alcoholism, whereas high t-PA was only observed in combination with disturbed liver function tests or with liver cirrhosis (two and sixfold above control values, respectively). A good correlation was observed between t-PA and gamma glutamyl transferase (r = 0.615; p <0.001). In patients with infectious hepatitis or with malignant disease of the liver t-PA was normal whereas u-PA and PAI-1 were increased.
PAI-2 levels were close to or below the detection limit (15 ng/ml) in the control group and in most patients. However, in two patients with alcohol induced cirrhosis PAI-2 levels were approximately 45 ng/ml and in one patient with hepatocarcinoma even 66 ng/ml. Thus, in liver disease, marked elevations of t-PA, u-PA and PAI-1 levels may occur, with increased PAI-1 as an early marker of liver defects and t-PA a marker of severe liver defects.
-
References
- 1 Francis RB, Feinstein DI. Clinical significance of accelerated fibrinolysis in liver disease. Haemostasis 1984; 14: 460-465
- 2 Aoki N, Yamanaka T. The alpha 2 plasmin inhibitor levels in liver disease. Clin Chim Acta 1978; 84: 99-105
- 3 Fletcher AP, Biederman O, Moore D, Alkjaersig N, Sherry S. Abnormal plasminogen-plasmin system activity (fibrinolysis) in patients with hepatic cirrhosis: its cause and consequences. J Clin Invest 1964; 43: 681-695
- 4 Hersch SL, Kunelis T, Francis RB. The pathogenesis of accelerated fibrinolysis in liver cirrhosis: a critical role for tissue plasminogen activator inhibitor. Blood 1987; 69: 1315-1319
- 5 Juhan-Vague I, Moerman B, De Cock F, Aillaud MF, Collen D. Plasma levels of a specific inhibitor of tissue-type plasminogen activator (and urokinase) in normal and pathological conditions. Thromb Res 1984; 33: 523-530
- 6 Brommer EJ P, Verheijen JH, Chang GT G, Rijken DC. Masking of fibrinolytic response to stimulation by an inhibitor of tissue-type plasminogen activator in plasma. Thromb Haemostas 1984; 52: 154-156
- 7 Kruithof EK O, Gudinchet A, Bachmann F. Plasminogen activator inhibitor 1 and plasminogen activator inhibitor 2 in various disease states. Thromb Haemostas 1988; 59: 7-12
- 8 Boks AL, Brommer EJ P, Schalm SW, Van Vliet HH D M. Hemostasis and fibrinolysis in severe liver failure and their relation to hemorrhage. Hepatology 1986; 6: 79-86
- 9 Kruithof EK O, Tran-Thang C, Gudinchet A, Hauert J, Nicoloso G, Genton C, Welti H, Bachmann F. Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors. Blood 1987; 69: 460-466
- 10 Kruithof EK O, Nicoloso G, Bachmann F. Plasminogen activator inhibitor 1: development of a radioimmunoassay and observations on its plasma concentration during venous occlusion and after platelet aggregation. Blood 1987; 70: 1645-1653
- 11 Snedecor GW, Cochran WG. Statistical Methods. Seventh edition Iowa State University Press; 1982
- 12 Kluft C, Verheijen JH, Jie AF H, Rijken DC, Preston FE, Sue-Ling HM, Jespersen J, Aasen AO. The postoperative fibrinolytic shutdown: a rapidly reverting acute phase pattern for the fast-acting inhibitor of tissue-type plasminogen activator. Scand J Clin Lab Invest 1985; 45: 605-610
- 13 Juhan-Vague I, Aillaud MF, De Cock F, Philip-Joet C, Arnaud C, Serradimigni A, Collen D. The fast-acting inhibitor of tissue-type plasminogen activator is an acute phase reactant protein. In: Progress in Fibrinolysis. (; 7). Davidson JF, Donati MB, Coccheri S. (eds) Churchill Livingstone; Edinburgh: 1985: 146-149
- 14 Bounameaux H, Stassen JM, Seghers C, Collen D. Influence of fibrin and liver blood flow on the turnover and the systemic fibrinogenolytic effects of recombinant human tissue-type plasminogen activator in rabbits. Blood 1986; 67: 1493-1497
- 15 Tajima H, Ishiguro J, Nonaka RK, Kurita M, Tanaka S, Ogawa N. Metabolic fate of urokinase. Chem Pharm Bull 1974; 22: 727-735
- 16 Som P, Rhodes BA, Bell WR. Radiolabelled streptokinase and urokinase and their comparative biodistribution. Thromb Res 1975; 6: 247-253
- 17 Emeis JJ. Fast hepatic clearance of tissue plasminogen activator inhibitor. Thromb Haemostas 1985; 54: 230 (Abstr)
- 18 Laug WE. Ethyl alcohol enhances plasminogen activator secretion by endothelial cells. J Am Med Assoc 1983; 250: 772-776
- 19 Meade TW, Chakrabarti R, Haines AP, North WR S, Stirling Y. Characteristics affecting fibrinolytic activity and plasma fibrinogen concentrations. Br Med J 1979; 1: 153-156