Download PDF
Thromb Haemost 1992; 68(03): 264-267
DOI: 10.1055/s-0038-1656362
Original Article
Schattauer GmbH Stuttgart

Activation of Coagulation and Fibrinolysis Following OKT3 Administration to Renal Transplant Recipients: Association with Distinct Mediators

Maarten H M Raasveld
1   The Renal Transplant Unit, Department of Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands
2   The Clinical Immunology Laboratory, Department of Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands
,
C Erik Hack
3   The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and the Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands
,
Ineke J M ten Berge
1   The Renal Transplant Unit, Department of Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands
2   The Clinical Immunology Laboratory, Department of Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 13 February 1992

Accepted after revision 21 April 1992

Publication Date:
04 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Treatment with OKT3 induces cytokine release and activates the complement system. Since both phenomena may affect coagulation and fibrinolysis we studied these systems in 8 renal transplant recipients during OKT3 treatment. In 8 of 9 patients a similar pattern was observed: plasma thrombin-antithrombin-III-complex, tissue-type plasminogen-activator and plasmin-α2-antiplasmin-complex levels were increased as compared to pretreatment levels (p <0.05) at 15 min after the first OKT3 dose and reached peak values at 1 h. No significant changes were observed upon subsequent OKT3 administrations or in a control group of 8 patients. In one patient upon the first OKT3 administration only complement activation, and no cytokine release was observed, whereas plasma thrombin-antithrombin-III-complex, tissue-type plasminogen-activator and plasmin-α2-antiplasmin-complex levels increased only at 15 min.

In conclusion, we demonstrate a biphasic activation of coagulation and fibrinolysis upon the first OKT3 dose; the initial phase seems to be associated with complement activation, the later phase with cytokine release.

 

  • References

  • 1 Ortho Multicenter Transplant Group A randomized clinical trial of OKT3 monoclonal antibody for acute rejection of cadaveric renal transplants. Ortho Multicenter Transplant Study Group. N Engl J Med 1985; 313: 337-342
    CrossrefPubMedGoogle Scholar
  • 2 Vigeral P, Chkoff N, Chatenoud L, Campos H, Lacombe M, Droz D, Goldstein G, Bach JF, Kreis H. Prophylactic use of OKT3 monoclonal antibody in cadaver kidney recipients. Utilization of OKT3 as the sole immunosuppressive agent. Transplantation 1986; 41: 730-733
    PubMedGoogle Scholar
  • 3 Abramowicz D, Schandene L, Goldman M, Crusiaux A, Vereerstreaten P, de Pauw L, Wybran J, Kinnaert P, Dupont E, Toussaint C. Release of tumor necrosis factor, interleukin-2 and gamma-interferon in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients. Transplantation 1989; 47: 606-608
    CrossrefPubMedGoogle Scholar
  • 4 Chatenoud L, Ferran C, Legendre C, Thouard I, Merote S, Reuter A, Gevaert Y, Kreis H, Franchimont P, Bach JF. In vivo cell activation following OKT3 administration. Transplantation 1990; 49: 697-702
    CrossrefPubMedGoogle Scholar
  • 5 Gaston RS, Deierhoi MH, Patterson T, Prasthofer E, Julian BA, Barber WH, Laskow DA, Diethelm AG, Curtis JJ. OKT3 first dose reaction: Association with T cell subsets and cytokine release. Kidney Int 1991; 39: 141-148
    CrossrefPubMedGoogle Scholar
  • 6 Bloemena E, ten Berge RJM, Surachno S, Wilmink JM. Kinetics of interleukin-6 during OKT3 treatment in renal allograft recipients. Transplantation 1990; 50: 330-331
    PubMedGoogle Scholar
  • 7 Muhlfelder TW, Niemetz J, Kreutzer D, Beebe D, Ward PA, Rosenfeld SI. Chemotactic fragment induces leukocyte production of tissue factor activity. J Clin Invest 1979; 63: 147-150
    CrossrefPubMedGoogle Scholar
  • 8 Prydz H, Allison AC, Schorlemmer HU. Further link between complement and blood coagulation. Nature 1977; 270: 173-174
    CrossrefPubMedGoogle Scholar
  • 9 Carson SD, Johnson DR. Consecutive enzyme cascades: complement activation at the cell surface triggers increased tissue factor activity. Blood 1990; 76: 361-367
    PubMedGoogle Scholar
  • 10 Osterud B, Rapaport SI. Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation. Proc Natl Acad Sci 1977; 74: 5260-5264
    CrossrefPubMedGoogle Scholar
  • 11 Bevilacqua MP, Pober JS, Majeau GR, Fiers W, Cotran RS, Gimbrone jr MA. Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin-1. Proc Natl Acad Sci USA 1986; 83: 4533-4537
    CrossrefPubMedGoogle Scholar
  • 12 Scarpati EM, Sadler JE. Regulation of endothelial cell coagulant properties. Modulation of tissue factor, plasminogen activator inhibitors and thrombomodulin by phorbol 12-myristate 13-acetate and tumor necrosis factor. J Biol Chem 1989; 264: 20705-20713
    PubMedGoogle Scholar
  • 13 Schleef RR, Bevilacqua MP, Sawdey M, Gimbrone Jr MA, Loskutoff DJ. Cytokine activation of vascular endothelium. Effects on tissue-type plasminogen activator and type 1 plasminogen activator inhibitor. J Biol Chem 1988; 263: 5797-5803
    PubMedGoogle Scholar
  • 14 Conway EM, Rosenberg RD. Tumor necrosis factor suppresses transcription of the thrombomodulin gene in endothelial cells. Mol Cell Biol 1988; 8: 5588-5592
    CrossrefPubMedGoogle Scholar
  • 15 Van Hinsbergh VWM, Van den Berg EA, Fiers W, Dooijewaard G. Tumor necrosis factor induces the production of urokinase-type plasminogen activator by human endothelial cells. Blood 1990; 75: 1991-1998
    PubMedGoogle Scholar
  • 16 Van der Poll T, Büller HR, ten Cate H, Wortel CH, Bauer KA, van Deventer SJH, Hack CE, Sauerwein HP, Rosenberg RD, ten Cate JW. Activation of coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med 1990; 32: 1622-1627
    PubMedGoogle Scholar
  • 17 Van der Poll T, Levi M, Büller HR, van Deventer SJH, de Boer JP, Hack CE, ten Cate JW. Fibrinolytic response to tumor necrosis factor in healthy subjects. J Exp Med 1991; 174: 729-732
    CrossrefPubMedGoogle Scholar
  • 18 Van Hinsbergh VWM, Bauer KA, Kooistra T, Kluft C, Dooijewaard G, Sherman ML, Nieuwenhuizen W. Progress of fibrinolysis during tumor necrosis factor infusions in humans. Concomitant increase in tissue-type plasminogen activator, plasminogen activator inhibitor type I, and fibrin(ogen) degradation products. Blood 1990; 76: 2284-2289
    PubMedGoogle Scholar
  • 19 Hack CE, Hannema AJ, Eerenberg AJM, Out TA, Aalberse RC. A C1-inhibitor-complex assay (INCA): a method to detect C1 activation in vitro and in vivo. J Immunol 1981; 127: 1450-1453
    PubMedGoogle Scholar
  • 20 Hoek JA, Sturk A, ten Cate JW, Lampin RJ, Berends F, Borm JJJ. Laboratory and clinical evaluation of an assay of thrombin-antithrombin-III complexes in plasma. Clin Chem 1988; 34: 2085-2092
    PubMedGoogle Scholar
  • 21 Nuijens JH, Huijbregts CCM, Eerenberg-Belmer AJM, Abbink JJ, Strack van Schijndel RJM, Felt-Bersma RJF, Thijs LG, Hack CE. Quantification of plasma XIIa-C1-inhibitor and kallikrein-C1-inhibitor complexes in sepsis. Blood 1988; 72: 1841-1848
    PubMedGoogle Scholar
  • 22 Van Zonneveld AJ, Veerman H, Brakenhoff JPJ, Aarden LA, Cajot F, Pannekoek H. Mapping of epitopes on human tissue-type plasminogen activator with recombinant deletion mutant proteins. Thromb Haemostas 1987; 57: 82-86
    PubMedGoogle Scholar
  • 23 Levi M, de Boer JP, Roem D, ten Cate JW, Hack CE. Plasminogen activation in vivo upon intravenous infusion of DDAVP. Quantitative assessment of plasmin-α2-antiplasmin complexes with a novel monoclonal antibody based radioimmunoassay. Thromb Haemostas 1992; 67: 111-116
    PubMedGoogle Scholar
  • 24 Hack CE, Paardekoper J, Eerenberg AJM, Navis GO, Nijsten MWN, Thijs LG, Nuijens JH. A modified competitive inhibition radioimmunoassay for the detection of C3a. Use of 125I-C3 instead of 125I-C3a. J Immunol Meth 1988; 107: 77-84
    PubMedGoogle Scholar
  • 25 Schrader J, Gallimore MJ, Eisenhauer T, Isemer FE, Schoel G, Warneke G, Brüggeman M, Scheler F. Parameters of the kallikrein-kinin, coagulation and fibrinolytic systems as early indicators of kidney transplant rejection. Nephron 1988; 48: 183-189
    CrossrefPubMedGoogle Scholar
  • 26 Thistlethwaite JR, Stuart JK, Mayes JT, Gaber AO, Woodle S, Buckingham MR, Stuart FP. Complications and monitoring of OKT3 therapy. Am J Kidney Dis 1988; 11: 112-119
    CrossrefPubMedGoogle Scholar
  • 27 Abramowicz D, Doutrelepont JM, Florquin S, de Pauw L, Pradier O, Marchant A, Kinnaert P, Goldman M, Vereerstraeten P. Comparison of 5 versus 10 mg/day of prophylactic OKT3 in renal transplantation. Abstract in: 5th Congress of the European Society for Organ Transplantation, Maastricht. The Netherlands: October 7–10 1991. p 166
    Google Scholar
  • 28 Emeis JJ. Mechanisms involved in short-term changes in blood levels of t-PA. In: Tissue-type Plasminogen Activator (t-PA): Physiological and Clinical Aspect, Vol II. Kluft C. (ed) CRC, Boca Raton, FL: 1988. pp 21-28
    Google Scholar
  • 29 Van Hinsbergh VWM, Sprengers ED, Kooistra T. Effect of thrombin on the production of plasminogen activators and PA inhibitor-1 by human foreskin microvascular endothelial cells. Thromb Haemostas 1987; 67: 148-153
    PubMedGoogle Scholar