Download PDF
Thromb Haemost 1989; 62(02): 686-689
DOI: 10.1055/s-0038-1646883
Original Article
Schattauer GmbH Stuttgart

DDAVP Induces Systemic Release of Urokinase-Type Plasminogen Activator

Marcel Levi
1   The Centre for Thrombosis, Hemostasis and Atherosclerosis Research, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
,
Jan W ten Cate
1   The Centre for Thrombosis, Hemostasis and Atherosclerosis Research, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
,
Gerard Dooijewaard
2   The Gaubius Institute TNO, Leiden, The Netherlands
,
Augueste Sturk
1   The Centre for Thrombosis, Hemostasis and Atherosclerosis Research, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
,
Emile J P Brommer
2   The Gaubius Institute TNO, Leiden, The Netherlands
,
Giancarlo Agnelli
3   The Istituto di Semeiotica Medica, Università di Perugia, Perugia, Italy
› Author Affiliations
Further Information

Publication History

Received 11 November 1988

Accepted after revision 05 April 1989

Publication Date:
30 June 2018 (online)

  PDF Download  Permissions and Reprints

Summary

The desamino-d-arginine vasopressin (DDAVP) induced enhancement of endogenous fibrinolysis is generally attributed to the release of tissue-type plasminogen activator (t-PA) from the vessel wall.

The observation of concurrent release of urokinase-type plasminogen activator (u-PA), which eventually might cooperate in the enhanced fibrinolytic activity, has not been reported thusfar.

In a preliminary study in two healthy human volunteers we found a 1.8-fold increase of urokinase-antigen (UK-antigen) and a 1.7-fold increase of plasmin-activatable pro-urokinase (pro-UK) activity to DDAVP intravenously. The plasma-peak levels coincided with the maximal t-PA level. These responses following infusion of DDAVP were subsequently confirmed in a randomized double blind cross-over study in six human volunteers. We conclude that u-PA is released by DDAVP concurrently with t-PA and that it is presumably from the same origin as t-PA i.e. endothelial cells. u-PA and t-PA may therefore cooperate in the enhanced fibrinolytic activity upon DDAVP infusion.

Keywords

DDAVP - Urokinase-type plasminogen activator - Fibrinolysis
 

  • References

  • 1 Cash JD, Gader AM A, De Costa J. Release of plasminogen activator and factor VIII to lysine vasopressin, arginine vasopressin, 1-Desamino-8-d-vasopressin, angiotensin and oxytocin in man. Br J Haematol 1974; 27: 363-364
    PubMedGoogle Scholar
  • 2 Mannucci PM, Rota L. Plasminogen activator response after DDAVP: a clinico-pharmacological study. Thromb Res 1980; 20: 69-76
    CrossrefPubMedGoogle Scholar
  • 3 Brommer EJ P, Barrett-Bergshoeff MM, Allen RA, Schicht J, Bertina RM, Schalekamp MA D H. The use of desmopressin acetate (DDAVP) as a test of the fibrinolytic capacity of patients. Analysis of responders and non-responders. Thromb Haemostas 1982; 48: 156-161
    PubMedGoogle Scholar
  • 4 Prowse CV, Farrugia A, Boulton F, Tucker J, Ludlam CA, McLaren M, Belck JJ F, Prentice CR M, Dawes J, Mac Gregor IR. A comparative study using immunological and biological assays of the haemostatic responses to DDAVP infusion, venous occlusion and exercise in normal men. Thromb Haemostas 1984; 51: 110-114
    PubMedGoogle Scholar
  • 5 Wun TC, Schleuning WD, Reich E. Isolation and characterization of urokinase from human plasma. J Biol Chem 1982; 157: 3276-3283
    PubMedGoogle Scholar
  • 6 Verheijen JH, Mullaart E, Chang GT G, Wijngaards G. A simple, sensitive spectrophotometric assay for extrinsic (tissue-type) plasminogen activator applicable to measurements in plasma. Thromb Haemostas 1982; 48: 266-269
    PubMedGoogle Scholar
  • 7 Binnema DJ, van Iersel JJ L, Dooijewaard G. Quantitation of urokinase antigen in plasma and culture media by use of an ELISA. Thromb Res 1986; 43: 569-577
    CrossrefPubMedGoogle Scholar
  • 8 Dooijewaard G, van Iersel JJ L, Brommer EJ P. Quantitation of pro-UK, UK and UK-inhibitor levels in plasma of patients and healthy man. Fibrinolysis 1986; 1 (suppl.) 142
    PubMedGoogle Scholar
  • 9 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: 684-687
    PubMedGoogle Scholar
  • 10 Simone JV, Vanderheiden J, Abildgaard CE. The semiautomatic one-stage factor VIII-assay with commercially prepared standard. J Lab Clin Med 1967; 69: 706-712
    PubMedGoogle Scholar
  • 11 Cejka J. Enzyme immunoassay for factor VIII-related antigen. Clin Chem 1982; 28: 1356-1358
    PubMedGoogle Scholar
  • 12 Brommer EJ P, Schicht J, Wijngaards G, Verheijen JH, Rijken DC. Fibrinolytic activators and inhibitors in terminal renal insufficiency and in anephric patients. Thromb Haemostas 1984; 52: 311-314
    PubMedGoogle Scholar
  • 13 Levin EG, Loskutoff DJ. Cultured bovine endothelial cells produce both urokinase and tissue-type plasminogen activators. J Cell Biol 1982; 94: 631-636
    CrossrefPubMedGoogle Scholar
  • 14 Booyse FM, Osikowicz G, Feder S, Scheinbuks J. Isolation and characterization of a urokinase-type plasminogen activator (Mr = 54,000) from cultured human endothelial cells indistinguishable from urinary urokinase. J Biol Chem 1984; 259: 7198-205
    PubMedGoogle Scholar
  • 15 Van Hinsberg VW M, Binnema D, Scheffer MA, Sprengers EW, Kooistra T, Rijken DC. Production of plasminogen activators and inhibitor by serially propagated endothelial cells from adult human blood vessels. Arteriosclerosis 1987; 7: 389
    CrossrefPubMedGoogle Scholar
  • 16 Moffat EH, Giddings JC, Bloom AL. The effect of desamino-d-arginine vasopressin 9DDAVP) and naloxone infusions on factor VIII and possible endothelial cell (EC) related activities. Br J Haematol 1984; 57: 651-662
    CrossrefPubMedGoogle Scholar
  • 17 Cash JD. Control mechanisms of activator release. In: Progress in chemical fibrinolysis and thrombolysis. (; 3). Davidson JF. (ed) Raven Press; New York: 1978: 65-67
    Google Scholar
  • 18 Prowse CV, Dow RC, Sheward WJ, Fink G, Boulton FE. The plasminogen activator response to drug infusion and to direct hypothalamic stimulation in dogs and rats. In: Progress in Fibrinolysis. David JF. (ed) Churchill Livingstone; Edinburgh: 1983: 104-110
    Google Scholar
  • 19 Juhan-Vague I, Conte-Devola B, Aillaud MF. Effects of DDAVP and venous occlusion on the release of tissue-type plasminogen activator and von Willebrand factor in patients with panhypopituitarism. Thromb Res 1984; 33: 653-659
    CrossrefPubMedGoogle Scholar
  • 20 Brommer EJ P. Storungen der Freisetzung des Plasminogenaktivators. Folia Haematol 1986; 113: 198-207
    PubMedGoogle Scholar
  • 21 Törnebohm E, Bratt G, Grangvist S, Lockner D, Egberg N. A pilot study: desmopressin (DDAVP) in the treatment of deep venous thrombosis. Thromb Res 1987; 45: 635-643
    CrossrefPubMedGoogle Scholar
  • 22 Nilsen DW T, Haerem J, Westheim A, Skjennald A, Grendahl H, Godal HC. Venous thrombosis following diagnostic transvenous catheterization by percutaneous catheter insertion: An evaluation of desmopressin as a thromboprophylactic agent. Thromb Haemostas 1984; 52: 121-123
    PubMedGoogle Scholar
  • 23 Zamarron C, Lijnen HR, Hoef Bv, Collen D. Biological and thrombolytic properties of pro-enzyme and active forms of human urokinase – I. Fibrinolytic and fibrinogenolytic properties in human plasma in vitro of urokinases obtained from human urine or by recombinant DNA technology. Thromb Haemostas 1984; 52: 19-23
    PubMedGoogle Scholar
  • 24 Gurewich V, Pannell R. A comparative study of the efficacy and specificity of tissue plasminogen activator and pro-urokinase: demonstration of synergism and of different thresholds of non-selectivity. Thromb Res 1986; 44: 217-228
    CrossrefPubMedGoogle Scholar
  • 25 Panell R, Black J, Gurewich V. Complementary modes of action of tissue-type plasminogen activator and pro-urokinase by which their synergistic effect on clot lysis may be explained. J Clin Invest 1988; 81: 853-859
    CrossrefPubMedGoogle Scholar
  • 26 Collen D, Stump DC, van de Werf F. Coronary thrombolysis in patients with acute myocardial infarction by intravenous infusion of synergic thrombolytic agents. Am Heart J 1986; 112: 1083-1084
    CrossrefPubMedGoogle Scholar