Thromb Haemost 1985; 54(04): 833-837
DOI: 10.1055/s-0038-1660143
Original Article
Schattauer GmbH Stuttgart

The Effect of Pentosan Polysulphate (SP54) on the Fibrinolytic Enzyme System - A Human Volunteer and Experimental Animal Study

N A Marsh
The Department of Physiology, King‘s College, University of London, London, UK
,
P M Peyser
The Department of Physiology, King‘s College, University of London, London, UK
,
L J Creighton
*   The Division of Blood Products, National Institute for Biological Standards and Control, London, UK
,
M Mahmoud
*   The Division of Blood Products, National Institute for Biological Standards and Control, London, UK
,
P J Gaffney
*   The Division of Blood Products, National Institute for Biological Standards and Control, London, UK
› Author Affiliations
Further Information

Publication History

Received 04 February 1985

Accepted 23 September 1985

Publication Date:
19 July 2018 (online)

Summary

Pentosan polysulphate causes an increase in plasminogen activator activity in plasma both after oral ingestion and after subcutaneous injection. The effect is greatest after 3 h and has disappeared by 6 h. Repeat doses by mouth over 5 days elicit a similar response. The recorded increase in activity is due largely to the release of tissue-type plasminogen activator (tPA) from the endothelium according to the antigen assay although there could be a small contribution from Factor XH-related “intrinsic” fibrinolysis induced in vitro. SP54 enhances activity ex vivo by a non-specific surface effect, and this phenomenon may contribute the increased levels of activity seen in vitro. Administration of SP54 to animals elicits a similar increase in activator activity, the intramuscular route being slightly more effective. Results with an inferior vena cava thrombosis model in the rat suggest that pentosan polysulphate may induce a thrombolytic effect.

 
  • References

  • 1 Halse Th. Aktivierung der Fibrinolyse und Thrombolyse durch Polysaccharidschwefelsaureester (Heparin, Heparinoide). Arzneim Forschung 1962; 12: 574-582
  • 2 Coccheri S, Gennari P, Loreti A. L“attivazione della fibrinolisi mediante polisaccaridi acidi. Clin Terap 1963; 25: 103-118
  • 3 Vinazzer H, Stemberger A, Haas S, Bliimel G. Influence of heparin; of different heparin fractions and of low molecular weight heparin-like substance on the mechanism of fibrinolysis. Thromb Res 1982; 27: 341-352
  • 4 Marsh NA, Gaffney PJ. The effect of pentosan polysulphate (SP54) on the fibrinolytic system of man. Thromb Haemostas 1983; 50: 83 Abstr
  • 5 Klocking HP, Markwardt F. Pentosan-polysulphate-induced release of plasminogen activator. Haemostasis 1984; 14: 121
  • 6 Bergqvist D, Efsing HO, Hallbook T, Lindblad B. Prevention of postoperative thromboembolic complications. A prospective comparison between Dextran 70, Dihydroergotamin-Heparin and a sulphated polysaccharid. Acta Chir Scand 1980; 146: 559-568
  • 7 Bergqvist D, Ljungner H. A comparative study of Dextran 70 and a sulphated polysaccharide in the prevention of postoperative thromboembolic complications. Br J Surg 1981; 68: 449-454
  • 8 Campani M. Farmaci attivatori della fibrinolisi. Minerva Chir 1963; 18: 1118-1127
  • 9 Menanteau A, Bruno M, Quilichini R, Nougarede M. Utilisation de l“heparinoide hemoclar dans le traitement des insuffisances cir-culatoires arterielles en neurologie (a propos de 78 cas). Marseille Med 1965; 192 no 11
  • 10 Viallefont H, Boudet C, Philippot M, Carrere M. Premiers resultats therapeutiques par l“Hemoclar en ophtalmologie. Bull Soc Ophtalm 1963; no 9-10
  • 11 Marangoni R, Ferrari A, Brera V. II trattamento dell“infarto miocar-dico con un farmaco attivatore della fibrinolisi (polisolfoestere del pentosano SP54) per infusione venosa lenta. Minerva Cardioangiol 1967; 15: 45-50
  • 12 Vinazzer H. Clinical and experimental data on the fibrinolytic action of pentosan polysulphate. Haemostasis 1984; 14: 122
  • 13 Fischer AM, Merton RE, Marsh NA, Williams S, Gaffney PJ, Barrowcliffe TW, Thomas DP. A comparison of pentosan polysulphate and heparin II: Effects of subcutaneous injection. Thromb Haemostas 1982; 47: 109-113
  • 14 Doutremepuich C, Gestreau JL, Maury MO, Quilichini R, Boisseau MR, Toulemonde F, Vairel E. Experimental venous thrombosis in rats treated with heparin and a low molecular weight heparin fraction. Haemostasis 1983; 13: 109-112
  • 15 Clark RG, Robinson ICAF. A system for long-term infusions in conscious rats. J Physiol 1984; 350: 2P
  • 16 Nilsson IM, Olow B. Fibrinolysis induced by streptokinase in man. Acta chir Scand 1962; 123: 247-266
  • 17 Marsh NA. Measurement of fibrinolytic capacity by the euglobulin lysis time method - a problem of “units”. Thromb Res 1977; 12: 197-200
  • 18 Marsh NA, Arocha-Pinango CL. Evaluation of the fibrin plate method for estimating plasminogen activators. Thrombos Diathes Haemorrh 1972; 28: 75-88
  • 19 Gaffney PJ, Curtis AD. A collaborative study of a proposed International Standard for tissue plasminogen activator (t-PA). Thromb Haemostas 1985; 53: 134-136
  • 20 Kluft C. Studies on the fibrinolytic system in human plasma: quantitative determination of plasminogen activators and proactivators. Thromb Haemostas 1979; 41: 365-383
  • 21 Rijken DC, Juhan-Vague I, de Cock F, Collen D. Measurement of human tissue-type plasminogen activator by a two-site immunoradiometric assay. J Lab Clin Med 1983; 101: 274-284
  • 22 Sampol J, Angles Cano E, Diner H, Benchimol P, Blachere A, Sultan Y. Effects of intravenous administration of pentosane polysulphate (Hemoclar) on coagulation and fibrinolysis in volunteers. Haemostasis 1984; 14: 121
  • 23 Keber D, Stegnar M, Keber I, Accetto B. Influence of moderate and strenuous daily physical activity on fibrinolytic activity of blood: possibility of plasminogen activator stores depletion. Thromb Haemostas 1979; 41: 745-755
  • 24 Astrup T, Rosa AT. A plasminogen proactivator-activator system in human blood effective in absence of Hageman factor. Thromb Res 1974; 4: 609-613
  • 25 Marsh NA, Gaffney PJ. Exercise-induced fibrinolysis - fact or fiction. Thromb Haemostas 1982; 48: 201-203
  • 26 Marsh NA, Gaffney PJ. Some observations on the release of extrinsic and intrinsic plasminogen activators during exercise in man. Haemostasis 1980; 9: 238-247
  • 27 Marsh NA. Fibrinolysis. 1981. John Wiley and Sons; Chichester:
  • 28 Jansen JWCM, Olieberg HH. The influence of several anaesthetics on the diluted blood clot lysis test of the rat. In: Progress in Fibrinolysis Davidson JF, Donati MB, Coccheri S. (Eds) Vol VII Churchill Livingstone, Edinburgh: 1985: 164-166
  • 29 Sandritter W, Schliiter G, Koppel G. Thrombolyse im Tierexperi-ment. Untersuchungen mit einen Polysaccharidsulfoester und Streptokinase. Med Welt 1964; 51: 2732-2739
  • 30 Fitzgerald DE, Szeto ILE, Spero J, Lewis JH. The thrombolytic effect of heparin and a heparin-like substance, SP54. Thrombos Diathes Haemorrh 1967; 17: 418-422
  • 31 Vairel EG, Bouty-Boye H, Toulemonde F, Doutremepuich C, Marsh NA, Gaffney PJ. Heparin and a low molecular weight fraction enhances thrombolysis and by this pathway exercises a protective effect against thrombosis. Thromb Res 1983; 30: 219-224