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DOI: 10.1055/s-0038-1646624
Additive Effect of dDAVP and Standard Heparin inIncreasing Plasma t-PA
Publikationsverlauf
Received 23. August 1988
Accepted after revision 10. März 1989
Publikationsdatum:
24. Juli 2018 (online)
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Summary
The aim of this study was to evaluate the existence of an additive effect between standard heparin and dDAVP in the enhancement of endogenous fibrinolysis. Eight healthy volunteers were studied in a randomized double blind placebo controlled cross-over trial. The volunteers were treated i. v. with dDAVP, 0.4 μg/kg, over 15 minutes followed by an i. v. bolus dose of either standard heparin, 5,000 I.U., or saline. A 48 hour wash-out period was adopted. The infusion of dDAVP followed by standard heparin resulted in a higher increase in plasma t-PA actiyity, t-PA antigen, circulating t-PA specific activity and FPLA when compared with dDAVP followed by saline. The difference was already statistically significant at 15 minutes after the infusion of dDAVP and lasted for up to 60 minutes after the end of the infusion of dDAVP. Plasma PAI 1 showed a slightly higher decrease after dDAVP plus standard heparin than after dDAVP plus saline but this difference was not statistically significant. No statistically significant changes of fibrinogen and α2-antiplasmin levels were observed. As expected, the infusion of standard heparin resulted in an increase in plasma anti-Xa activity and in a prolongation of aPTT Our results demonstrated an additive effect of dDAVP and standard heparin on the increase in circulating t-PA, the effect of dDAVP being potentiated and prolonged by heparin. This observation could prospect a combined use of dDAVP and standard heparin in the prophylaxis and treatment of thromboembolic diseases.
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References
- 1 Prowse CV, Cash JD. Physiologic and pharmacologic enhancement of fibrinolysis. Sem Thromb Hemostas 1984; 10: 51-56
- 2 Gader AM A, Da Costa J, Cash JD. A new vasopressin analogue and fibrinolysis. Lancet 1973; 2: 1417-1418
- 3 Mannucci PM, Aberg M, Nilsson IM, Robertson B. Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs. Br J Haematol 1975; 30: 81-93
- 4 Nilsson IM, Holmberg L, Aberg M, Vilhardt H. The release of plasminogen activator and factor VIII after injection of dDAVP in healthy volunteers and in patients with von Willebrand’s disease. Scand J Haematol 1980; 24: 351-359
- 5 Brommer EJ P, Barrett-Bergshoeff MM, Allen RA, Schicht I, 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
- 6 Mannucci PM, Ruggeri ZM, Pareti FI, Capitanio A. l-Deamino-8-D-arginine vasopressin: a new pharmacological approach to the management of hemophilia and von Willebrand’s disease. Lancet 1977; 1: 869-872
- 7 Agnelli G, Borm J, Cosmi B, Levi M, ten Cate JW. Effects of standard heparin and a low molecular weight heparin (Kabi 2165) on fibrinolysis. Thromb Haemostas 1988; 60: 311-313
- 8 Verheijen HJ, Mullaart E, Chang GT G, Kluft C, Wijngaards G. A simple, sensitive spectrophotometric assay for extrinsic (tissue type) plasminogen activator applicable to measurement in plasma. Thromb Haemostas 1982; 48: 266-269
- 9 Kluft C. C1-inactivator-resistant fibrinolytic activity in plasma eu- globulin fraction: its relation to vascular activator in blood and its role in euglobulin fibrinolysis. Thromb Res 1978; 13: 135-151
- 10 Gaffney PJ, Curtis AD. A collaborative study of a proposed international standard for tissue-type plasminogen activator. Thromb Haemostas 1985; 53: 134-136
- 11 Holvoet P, Cleemput H, Collen D. Assay of human tissue-type plasminogen activator (t-PA) based on three murine monoclonal antibodies to t-PA. Thromb Haemostas 1985; 54: 684-689
- 12 MacGregor IR, Roberts EM, Prowse CV, Broomhead AF, Ozolins M, Litka P. Fibrinolytic and haemostatic responses to desamino-D- arginine vasopressin (dDAVP) administered by intravenous and subcutaneous routes in healthy subjects. Thromb Haemostas 1988; 59: 34-39
- 13 Chakrabarti R, Bielawiec M, Evans JF, Fearnley GR. Methodological study and recommended tecnique for determining the euglobulin lysis time. J Clin Pathol 1968; 21: 698-701
- 14 Teger-Nielsson AC, Friberger P, Gyzander E. Determination of a new rapid plasmin inhibitor in human blood by means of a plasmin specific tripeptide substrate. Scand J Lab Invest 1977; 37: 403-409
- 15 Teien AN, Lie M, Abilgaard U. Assay of heparin in plasma using a chromogenic substrate for activated factor X. Thromb Res 1976; 8: 413-418
- 16 Laurell CB. Electroimmunoassay. Scand J Clin Lab Invest 1972; 29 S124 21-37
- 17 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-246
- 18 Dunnett CW. A multiple comparisons procedure for comparing several treatments with a control. J Am Stat Assoc 1955; 50: 1096-1099
- 19 Andrade-Gordon P, Strickland S. Interaction of heparin with plasminogen activators and plasminogen: effects on the activation of plasminogen. Biochemistry 1986; 25: 4033-4040
- 20 Verstraete M, Bounameaux H, de Cock F, van de Werf F, Collen D. Pharmacokinetics and systemic fibrinogenolytic effect of recombinant human tissue-type plasminogen activator (rt-PA) in humans. J Pharmacol Exp Ther 1985; 235: 506-512
- 21 Wiman B, Mellbring G, Ranby M. Plasminogen activator release during venous stasis and exercise as determined by a new specific assay. Clin Chim Acta 1983; 127: 279-288
- 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
- 23 Tomebohm E, Bratt G, Granqvist S, Lockner D, Egberg N. A pilot study: desmopressin in the treatment of deep venous thrombosis. Thromb Res 1987 45: 635-643