Download PDF
Thromb Haemost 1992; 67(01): 101-105
DOI: 10.1055/s-0038-1648388
Original Articles
Schattauer GmbH Stuttgart

The Amount of Plasminogen, Tissue-Type Plasminogen Activator and Plasminogen Activator Inhibitor Type 1 in Human Thrombi and the Relation to IVVO-TNO Lysibility

B J Potter van Loon
1   The Westeinde Hospital, Dept. of lnternal Medicine, Den Haag, The Netherlands
2   The Gaubius Laboratory, IVVO-TNO, Leiden, The Netherlands
,
D C Rijken
2   The Gaubius Laboratory, IVVO-TNO, Leiden, The Netherlands
,
E J P Brommer
2   The Gaubius Laboratory, IVVO-TNO, Leiden, The Netherlands
,
A P C van der Maas
1   The Westeinde Hospital, Dept. of lnternal Medicine, Den Haag, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 23 April 1991

Accepted after revision 18 July 1991

Publication Date:
02 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Thrombolytic therapy successfully reopens obstructed blood vessels in the majority of cases. However, it is not known why a substantial amount of thrombi are resistant to lysis by a fibrinolytic agent. In vitro studies have demonstrated that tissue-type plasminogen activator (t-PA) and plasminogen incorporated in the clot (during formation) increase lysibility. To test whether lysibility of in vivo formed human thrombi is related to their composition, we studied 25 venous thrombi obtained at autopsy and 21 arterial thrombi obtained during embolectomy.

Plasminogen activator inhibitor-1 (PAI-1) antigen was measured in a phosphate-buffered saline (PBS) extract of each thrombus; t-PA antigen and plasminogen antigen were determined in a 6 M urea extract of the thrombus, representing bound proteins. Lysibility was measured as weight reduction during 8 h of incubation in PBS containing streptokinase (SK) 100 U/ml, corrected for spontaneous lysis, reflected by weight loss in PBS without SK. In addition, lysibility in SK was compared with lysibility in urokinase (UK) 100 U/ml and in t-PA 200 U/ml.

Spontaneous lysis amounted to 29 ± 5% (mean ± SEM) and 33 ± 5% in venous and arterial thrombi, respectively, and inversely correlated with the PAI-1 content of thrombi (r = —0.43, p <0.01). Lysibility amounted to 76 ± 6% in venous and 90 ± 4% in arterial thrombi (venous vs. arterial: p = 0.051). PAI-1-, plasminogen- and t-PA-content of venous thrombi were 902 ± 129 ng, 34.3 ± 4.8 pg and 26.7 ± 3.0 ng per gram of wet thrombus respectively; for arterial thrombi these values were 2,031 ± 401 ng/g (p = 0.011), 64.1 ± 11.4 pg/g (p = 0.088) and 62.2 ± 8.3 ng/g (p = 0.0001), respectively. A correlation was found between t-PA and plasminogen (r = 0.74, p <0.001). Lysibility by SK related to plasminogen content in both venous (r = 0.60, p <0.002) and arterial (r = 0.44, p <0.05) thrombi; PAI-1 and t-PA did not correlate with lysibility. Lysibility in the chosen concentrations of SK, UK and t-PA were similar.

We conclude that spontaneous lysis of thrombi in saline is dependent on PAI-1 content and that susceptibility of thrombibi to lysis by SK ex vivo is dependent on the plasminogen content

 

  • References

  • 1 Marder VJ, Sherry S. Thrombolytic therapy: Current status. N Engl J Med 1988; 318: 1512-1521 1585-95
    CrossrefPubMedGoogle Scholar
  • 2 Chesterman CN. Thrombolytic therapy. In: Haemostasis and Thrombosis. 2nd. ed. Bloom AL, Thomas DP. (eds). Churchill Livingstone; London: 1987. pp 829-848
    Google Scholar
  • 3 Hess H, Ingrisch H, Mietaschk A, Rath H. Local low-dose thrombolytic therapy of peripheral arterial occlusions. N Engl J Med 1982; 307: 1627-1630
    CrossrefPubMedGoogle Scholar
  • 4 Gottlob R. Plasminogen and plasma plasmin inhibitors in arterial and venous thrombi of various ages. In: Progress in Chemical Fibrinolysis and Thrombolysis, Vol. 1. Davidson JF, Samama MM, Desnoyers PC. (eds). Raven Press; New York: 1975. pp 23-36
    Google Scholar
  • 5 Tibbutt DA, Williams EW, Walker MW, Chesterman CN, Holt JM, Sharp AA. Controlled trial of Ancrod and streptokinase in the treatment of deep vein thrombosis of the lower limb. Br J Haemostas 1974; 27: 407-414
    PubMedGoogle Scholar
  • 6 Arnesen H, Heilo A, Jakobsen E, Ly B, Skaga E. A prospective study of streptokinase in the treatment of deep vein thrombosis. Acta Med Scand 1978; 203: 457-463
    PubMedGoogle Scholar
  • 7 Weimar W, Stibbe J, van Seyen AJ, Billiau A, De Somer P, Collen D. Specific lysis of an ileofemoral thrombus by administration of extrinsic (tissue-type) plasminogen activator. Lancet 1981; ii: 1018-1020
    PubMedGoogle Scholar
  • 8 Luomanmàki K, Halttunen PK, Hekali P, Valle M, Heikkilà J. Experience with streptokinase treatment of major pulmonary embolism. Ann Clin Res 1983; 15: 21-25
    PubMedGoogle Scholar
  • 9 Robinson JA, Carty GA, Burch BH. Factors predicting the outcome of regional streptokinase therapy for peripheral arterial occlusions. Surg Gynaecol Obstet 1985; 161: 453-456
    PubMedGoogle Scholar
  • 10 Tran-Thang C, Kruithof EKO, Bachmann F. Tissue-type plasminogen activator increases the binding of Glu-plasminogen to clots. J Clin Invest 1984; 74: 2009-2016
    CrossrefPubMedGoogle Scholar
  • 11 Zamarron C, Albert A. Adsorbed plasminogen and fibrinolysis rate of recent and aged plasma clots. Haemostasis 1981; 10: 59 (abstr).
    PubMedGoogle Scholar
  • 12 Chevalet-Prandini MH, Chapel A, Suscillon A. The fibrinolytic action of flufenamate and its influence on plasminogen binding to fibrin. Thromb Res 1985; 38: 481-489
    CrossrefPubMedGoogle Scholar
  • 13 Brommer EJP. The level of extrinsic plasminogen activator (t-PA) during clotting determines the rate of fibrinolysis; inefficiency of activators added afterwards. Thromb Res 1984; 34: 109-115
    CrossrefPubMedGoogle Scholar
  • 14 Tran-Thang C, Kruithof EKO, Bachmann F. The mechanism of in vitro clot lysis induced by vascular plasminogen activator. Blood 1984; 63: 1331-1337
    PubMedGoogle Scholar
  • 15 Brommer EJP, Verheijen JH, Chang GTC, Rijken DC. Masking of fibrinolytic response to stimulation by an inhibitor of tissue-type plasminogen activator in plasma. Thromb Haemostas 1984; 52: 154-156
    PubMedGoogle Scholar
  • 16 Sprengers ED, Kluft C. Plasminogen activator inhibitors. Blood 1987; 69: 381-387
    PubMedGoogle Scholar
  • 17 Booth NA, Croll A, Bennett B. The activity of plasminogen activator inhibitor-1 (PAI-1) of human platelet. Fibrinolysis 1990; 4 (Supp) (12) 138-140
    PubMedGoogle Scholar
  • 18 Hedner U, Nilsson IM, Robertson B. Determination of plasminogen in clots and thrombi. Thromb Diath Haem 1966; 16: 38-50
    PubMedGoogle Scholar
  • 19 Ogston D, Ogston CM, Fullerton HW. The plasminogen content of thrombi. Thromb Diath Haemorrh 1966; 15: 220-230
    PubMedGoogle Scholar
  • 20 Alkjaersig N, Fletcher AP, Sherry S. The mechanism of clot dissolution by plasmin. J Clin Invest 1959; 38: 1086-1095
    CrossrefPubMedGoogle Scholar
  • 21 Sabovic M, Lijnen HR, Keber D, Collen D. Effect of retraction on the lysis of human clots with fibrin specific and non-fibrin specific plasminogen activators. Thromb Haemostas 1989; 62: 1083-1087
    PubMedGoogle Scholar
  • 22 Sabovic M, Lijnen HR, Keber D, Collen D. Correlation between progressive adsorption of plasminogen to blood clots and their sensitivity to lysis. Thromb Haemostas 1990; 64: 450-454
    PubMedGoogle Scholar
  • 23 Suenson E, Lutzen O, Thorsen S. Initial plasmin-degradation of fibrin as the basis of a positive feed-back mechanism in fibrinolysis. Eur J Biochem 1984; 140: 513-522
    CrossrefPubMedGoogle Scholar
  • 24 Brommer EJP, Boks AL, Koopman J, Haverkate F. Protraction of whole blood and plasma clot lysis in patients with high levels of an inhibitor of tissue-type plasminogen activator. Thromb Res 1985; 39: 271-280
    CrossrefPubMedGoogle Scholar
  • 25 Knabb RM, Chiu AT, Reilly TM. Effects of recombinant plasminogen activator inhibitor type 1 on fibrinolysis in vitro and in vivo. Thromb Res 1990; 59: 309-317
    CrossrefPubMedGoogle Scholar
  • 26 Noordhoek Hegt V. Distribution and variation of fibrinolytic activity in the walls of human arteries and veins. In: Histochemical Studies on Vascular Fibrinolysis. Haemostasis 1976; 5: 355-372
    PubMedGoogle Scholar
  • 27 Ranby M, Nguyen G, Scarabin PY, Samama M. Immunoreactivity of tissue plasminogen activator and of its inhibitor complexes. Thromb Haemostas 1989; 61: 409-414
    PubMedGoogle Scholar
  • 28 Keber D, Sabovic M, Stendler M, Stegnar M. Dissolution of “ex vivo” thrombi by tissue plasminogen activator, streptokinase and urokinase. Thromb Res 1986; Suppl VI 109
    PubMedGoogle Scholar