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Thromb Haemost 1991; 66(04): 426-429
DOI: 10.1055/s-0038-1646432
Review Article
Schattauer GmbH Stuttgart

Deep Vein Thrombosis and Fibrinolysis

Defective Urokinase Type Plasminogen Activator Release
Marcel Levi
1   The Centre for Thrombosis, Haemostasis and Atherosclerosis Research, Academic Medical Center, Amsterdam, The Netherlands
,
Anthonie W A Lensing
1   The Centre for Thrombosis, Haemostasis and Atherosclerosis Research, Academic Medical Center, Amsterdam, The Netherlands
,
Harry R Büller
1   The Centre for Thrombosis, Haemostasis and Atherosclerosis Research, Academic Medical Center, Amsterdam, The Netherlands
,
Paolo Prandoni
2   The Institute of Internal Medicine, University of Padua, Padua, Italy
,
Gerard Dooijewaard
3   The Gaubius Institute TNO, Leiden, The Netherlands
,
Stefano Cuppini
2   The Institute of Internal Medicine, University of Padua, Padua, Italy
,
Jan Wouter ten Cate
1   The Centre for Thrombosis, Haemostasis and Atherosclerosis Research, Academic Medical Center, Amsterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 21 November 1990

Accepted 09 April 1991

Publication Date:
25 July 2018 (online)

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Summary

In the present study 57 consecutive patients with a first episode of venographically proven deep vein thrombosis were investigated to evaluate the release of tissue-type plasminogen activator (t-PA) and of urokinase-type plasminogen activator (u-PA) in response to DDAVP stimulation as well as the resting plasminogen activator inhibitor (PAI) concentration, comparing this to the results obtained in 66 similar patients with a clinical suspicion of thrombosis but with a normal venogram. All assays were performed without knowledge of the patient's status.

Four patients in the deep vein thrombosis-group (7%) had an absent u-PA antigen response upon DDAVP infusion, while a normal response was observed in all control subjects. Patients and controls showed similar increases in t-PA antigen level upon DDAVP. High resting PAI antigen levels were encountered in 5 patients in the deep vein thrombosis-group (9%) and in 6 subjects in the control group (9%).

The results from this controlled study indicate that a defective release of u-PA may occur in patients with deep vein thrombosis and may have pathogenetic significance. Furthermore it is concluded that elevation of PAI levels cannot be considered as a specific risk factor for venous thrombosis.

 

  • References

  • 1 Bauer KA, Goodman TL, Kass BL, Rosenberg RD. Elevated factor Xa activity in the blood of asymptomatic patients with congenital antithrombin deficiency. J Clin Invest 1985; 76: 826-9
    CrossrefPubMedSearch in Google Scholar
  • 2 Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thromb Diath Haemorrh 1965; 13: 516-30
    PubMedSearch in Google Scholar
  • 3 Griffin JH, Evatt B, Zimmermann TS, Kleiss AJ, Widemann C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68: 1370-3
    CrossrefPubMedSearch in Google Scholar
  • 4 Comp PC, Nixon RR, Cooper MR, Esmon CT. Familial protein C deficiency is associated with recurrent thrombosis. J Clin Invest 1984; 74: 2082-8
    CrossrefPubMedSearch in Google Scholar
  • 5 Isacson I, Nilsson IM. Defective fibrinolysis in blood and vein walls in recurrent "idiopathic" venous thrombosis. Acta Chir Scand 1972; 138: 313-9
    PubMedSearch in Google Scholar
  • 6 Korninger C, Lechner K, Niessner H, Gössinger H, Kundi M. Impaired fibrinolytic capacity predisposes for recurrence of venous thrombosis. Thromb Haemostas 1984; 52: 127-30
    PubMedSearch in Google Scholar
  • 7 Wiman B, Ljungberg B, Chmielewska J, Urdén J, Blombôck M, Johnsson H. The role of the fibrinolytic system in deep vein thrombosis. J Lab Clin Med 1985; 105: 265-70
    PubMedSearch in Google Scholar
  • 8 Lijnen HR, Collen D. Congenital and acquired deficiencies of components of the fibrinolytic system and their relation to bleeding or thrombosis. Fibrinolysis 1989; 3: 67-77
    PubMedSearch in Google Scholar
  • 9 Aoki N, Moroi M, Sakata Y, Yoshida N, Matsuda M. Abnormal plasminogen. A hereditary molecular abnormality found in a patient with recurrent thrombosis. J Clin Invest 1978; 61: 1186-95
    CrossrefPubMedSearch in Google Scholar
  • 10 Mannucci PM, Kluft C, Traas DW, Seveso P, D'Angelo A. Congenital plasminogen deficiency associated with venous thromboembolism. Br J Haematol 1986; 63: 753-9
    CrossrefPubMedSearch in Google Scholar
  • 11 Egeberg O. Inherited fibrinogen abnormality causing thrombophilia. Thromb Diath Haemorrh 1967; 17: 176-87
    PubMedSearch in Google Scholar
  • 12 Darras V, Thienpont M, Stump DC, Collen D. Measurement of urokinase-type plasminogen activator (u-PA) with an enzyme-linked immunosorbent assay (ELISA) based on three murine monoclonal antibodies. Thromb Haemostas 1986; 56: 411-4
    PubMedSearch in Google Scholar
  • 13 Dooijewaard G, de Boer A, Turion PNC, Cohen AF, Breimer DD, Kluft C. Physical exercise induces enhancement of urokinase-type plasminogen activator (u-PA) levels in plasma. Thromb Haemostas 1991; 65: 82-6
    PubMedSearch in Google Scholar
  • 14 Mannucci PM, Rota L. Plasminogen activator response after DDAVP: a clinico-pharmacological study. Thromb Res 1980; 20: 69-76
    CrossrefPubMedSearch in Google Scholar
  • 15 Levi M, ten Cate JW, Dooijewaard G, Sturk A, Brommer EJP, Agnelli G. DDAVP induces systemic release of urokinase-type plasminogen activator. Thromb Haemostas 1989; 62: 686-9
    PubMedSearch in Google Scholar
  • 16 Juhan Vague I, Valadier J, Alessi MC, Aillaud MF, Ansaldi J, Philip Joet C, Holvoet P, Serradimigni A, Collen D. Deficient t-PA release and elevated PA inhibitor levels in patients with spontaneous or recurrent deep vein thrombosis. Thromb Haemostas 1987; 57: 67-72
    PubMedSearch in Google Scholar
  • 17 Stead N, Bauer KA, Kinney TR, Lewis JG, Campbell EE, Shifman MA, Rosenberg RD, Pizzo SV. Venous thrombosis in a family with defective release of vascular plasminogen activator and elevated plasma factor VIII/von Willebrand's factor. Am J Med 1984; 84: 33-9
    PubMedSearch in Google Scholar
  • 18 Nilsson IM, Ljungnér H, Tengborn L. Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor. Br Med J 1985; 290: 1453-6
    CrossrefPubMedSearch in Google Scholar
  • 19 Lensing AWA, Prandoni P, Brandjes D, Huisman PM, Vigo M, ten Cate JW, Huisman MV, Büller HR. Detection of deep-vein thrombosis by real-time B-mode ultrasonography. N Engl J Med 1989; 320: 342-5
    CrossrefPubMedSearch in Google Scholar
  • 20 Rabinov K, Paulin S. Roentgen diagnosis of venous thrombosis in the leg. Arch Surg 1972; 104: 134-44
    CrossrefPubMedSearch in Google Scholar
  • 21 Binnema DJ, van Iersel JJL, Dooijewaard G. Quantitation of urokinase antigen in plasma and culture media by use of an ELISA. Thromb Res 1986; 43: 569-77
    CrossrefPubMedSearch in Google Scholar
  • 22 Rodbard D. Statistical estimation of the minimal detectable concentration ("sensitivity") for radio-ligand assays. Analyt Biochem 1978; 90: 1-12
    CrossrefPubMedSearch in Google Scholar
  • 23 Holvoet P, Cleemput H, Collen D. Assay of human tissue-type plasminogen activator (t-PA) with an enzyme-linked immunosorbent assay (ELISA) based on three murine monoclonal antibodies to t-PA. Thromb Haemostas 1985; 54: 684-7
    PubMedSearch in Google Scholar
  • 24 Verheijen JH, Mullaart E, Chang GTG, Kluft C, Wijngaards G. A simple, sensitive spectrophotometric assay for extrinsic (tissue-type) plasminogen activator applicable to measurements in plasma. Thromb Haemostas 1982; 48: 266-9
    PubMedSearch in Google Scholar
  • 25 Engesser L, Brommer EJP, Kluft C, Briet E. Elevated plasminogen activator inhibitor (PAI), a cause of thrombophilia? – A study in 203 patients with familial or sporadic venous thrombophilia. Thromb Haemostas 1989; 62: 673-80
    PubMedSearch in Google Scholar
  • 26 Paramo JA, Colucci M, Collen D. Plasminogen activator inhibitor in the blood of patients with coronary artery disease. Br Med J 1985; 291: 573-4
    CrossrefPubMedSearch in Google Scholar
  • 27 Hamsten A, Wiman B, De Faire U, Blombôck M. Increased levels of a rapid inhibitor of tissue plasminogen activator in young survivors of acute myocardial infarction. N Engl J Med 1985; 313: 1557-63
    CrossrefPubMedSearch in Google Scholar