Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 Oct;88(4):1155–1160. doi: 10.1172/JCI115416

Reduction of contact activation related fibrinolytic activity in factor XII deficient patients. Further evidence for the role of the contact system in fibrinolysis in vivo.

M Levi 1, C E Hack 1, J P de Boer 1, D P Brandjes 1, H R Büller 1, J W ten Cate 1
PMCID: PMC295573  PMID: 1833421

Abstract

In this study the contribution of activation of the contact system to activation of the fibrinolytic system in vivo was investigated in healthy volunteers and in factor XII deficient patients. The plasminogen activating activity in plasma from healthy volunteers after infusion of desamino D-arginine vasopressin (DDAVP) was only partially blocked (for 77%) with specific antibodies to tissue-type plasminogen activator and urokinase type plasminogen activator. The residual activity could be quenched by a monoclonal antibody that inhibits factor XII activity and was not present in patients with a factor XII deficiency. The formation of plasmin upon the DDAVP stimulus as reflected by circulating plasmin-alpha 2-antiplasmin complexes was lower in factor XII deficient patients than in healthy volunteers. Activation of the contact system occurred after DDAVP infusion in healthy volunteers and was absent in factor XII deficient patients. These results indicate that DDAVP induces a plasminogen activating activity that is partially dependent on activation of the contact system and that contributes to the overall fibrinolytic activity as indicated by the formation of plasmin-alpha 2-antiplasmin complexes. This fibrinolytic activity is impaired in factor XII deficient patients which may explain the occurrence of thromboembolic complications in these patients.

Full text

PDF
1155

Images in this article

1157Image
on p.1157
1157Image
on p.1157
1157Image
on p.1157

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Binnema D. J., Dooijewaard G., van Iersel J. J., Turion P. N., Kluft C. The contact-system dependent plasminogen activator from human plasma: identification and characterization. Thromb Haemost. 1990 Nov 30;64(3):390–397. [PubMed] [Google Scholar]
  2. Binnema D. J., van Iersel J. J., Dooijewaard G. Quantitation of urokinase antigen in plasma and culture media by use of an ELISA. Thromb Res. 1986 Sep 1;43(5):569–577. doi: 10.1016/0049-3848(86)90077-0. [DOI] [PubMed] [Google Scholar]
  3. Brommer E. J., Kluft C., Bertina R. M., Alderkamp G. H. Effect of DDAVP on plasma levels of factor VII and XII. Br J Haematol. 1984 May;57(1):173–175. doi: 10.1111/j.1365-2141.1984.tb02878.x. [DOI] [PubMed] [Google Scholar]
  4. Collen D. On the regulation and control of fibrinolysis. Edward Kowalski Memorial Lecture. Thromb Haemost. 1980 Jun 18;43(2):77–89. [PubMed] [Google Scholar]
  5. Colman R. W. Surface-mediated defense reactions. The plasma contact activation system. J Clin Invest. 1984 May;73(5):1249–1253. doi: 10.1172/JCI111326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cool D. E., Edgell C. J., Louie G. V., Zoller M. J., Brayer G. D., MacGillivray R. T. Characterization of human blood coagulation factor XII cDNA. Prediction of the primary structure of factor XII and the tertiary structure of beta-factor XIIa. J Biol Chem. 1985 Nov 5;260(25):13666–13676. [PubMed] [Google Scholar]
  7. Emeis J. J. Perfused rat hindlegs. A model to study plasminogen activator release. Thromb Res. 1983 May 1;30(3):195–203. doi: 10.1016/0049-3848(83)90072-5. [DOI] [PubMed] [Google Scholar]
  8. Goldsmith G. H., Jr, Saito H., Ratnoff O. S. The activation of plasminogen by Hageman factor (Factor XII) and Hageman factor fragments. J Clin Invest. 1978 Jul;62(1):54–60. doi: 10.1172/JCI109113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goodnough L. T., Saito H., Ratnoff O. D. Thrombosis or myocardial infarction in congenital clotting factor abnormalities and chronic thrombocytopenias: a report of 21 patients and a review of 50 previously reported cases. Medicine (Baltimore) 1983 Jul;62(4):248–255. doi: 10.1097/00005792-198307000-00004. [DOI] [PubMed] [Google Scholar]
  10. Griffin J. H. Role of surface in surface-dependent activation of Hageman factor (blood coagulation factor XII). Proc Natl Acad Sci U S A. 1978 Apr;75(4):1998–2002. doi: 10.1073/pnas.75.4.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hack C. E., Hannema A. J., Eerenberg-Belmer A. J., Out T. A., Aalberse R. C. A C1-inhibitor-complex assay (INCA): a method to detect C1 activation in vitro and in vivo. J Immunol. 1981 Oct;127(4):1450–1453. [PubMed] [Google Scholar]
  12. Hauert J., Nicoloso G., Schleuning W. D., Bachmann F., Schapira M. Plasminogen activators in dextran sulfate-activated euglobulin fractions: a molecular analysis of factor XII- and prekallikrein-dependent fibrinolysis. Blood. 1989 Mar;73(4):994–999. [PubMed] [Google Scholar]
  13. 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 Haemost. 1985 Oct 30;54(3):684–687. [PubMed] [Google Scholar]
  14. Kaplan A. P., Austen K. F. A prealbumin activator of prekallikrein. II. Derivation of activators of prekallikrein from active Hageman factor by digestion with plasmin. J Exp Med. 1971 Apr 1;133(4):696–712. doi: 10.1084/jem.133.4.696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kaplan A. P., Silverberg M. The coagulation-kinin pathway of human plasma. Blood. 1987 Jul;70(1):1–15. [PubMed] [Google Scholar]
  16. Kluft C., Dooijewaard G., Emeis J. J. Role of the contact system in fibrinolysis. Semin Thromb Hemost. 1987 Jan;13(1):50–68. doi: 10.1055/s-2007-1003475. [DOI] [PubMed] [Google Scholar]
  17. Levi M., ten Cate J. W., Dooijewaard G., Sturk A., Brommer E. J., Agnelli G. DDAVP induces systemic release of urokinase-type plasminogen activator. Thromb Haemost. 1989 Sep 29;62(2):686–689. [PubMed] [Google Scholar]
  18. Lämmle B., Wuillemin W. A., Huber I., Krauskopf M., Zürcher C., Pflugshaupt R., Furlan M. Thromboembolism and bleeding tendency in congenital factor XII deficiency--a study on 74 subjects from 14 Swiss families. Thromb Haemost. 1991 Feb 12;65(2):117–121. [PubMed] [Google Scholar]
  19. Mandle R. J., Jr, Kaplan A. P. Hageman-factor-dependent fibrinolysis: generation of fibrinolytic activity by the interaction of human activated factor XI and plasminogen. Blood. 1979 Oct;54(4):850–862. [PubMed] [Google Scholar]
  20. Mannucci P. M., Rota L. Plasminogen activator response after DDAVP: a clinico-pharmacological study. Thromb Res. 1980 Oct 1;20(1):69–76. doi: 10.1016/0049-3848(80)90057-2. [DOI] [PubMed] [Google Scholar]
  21. Nenci G. G., Berrettini M., De Cunto M., Agnelli G. Effect of DDAVP on plasma level of factor XII. Br J Haematol. 1983 Jul;54(3):489–492. doi: 10.1111/j.1365-2141.1983.tb02124.x. [DOI] [PubMed] [Google Scholar]
  22. Nilsson T., Bäck O. Elevated plasmin-alpha 2-antiplasmin complex levels in hereditary angioedema: evidence for the in vivo efficiency of the intrinsic fibrinolytic system. Thromb Res. 1985 Dec 15;40(6):817–821. doi: 10.1016/0049-3848(85)90318-4. [DOI] [PubMed] [Google Scholar]
  23. Nuijens J. H., Huijbregts C. C., Eerenberg-Belmer A. J., Abbink J. J., Strack van Schijndel R. J., Felt-Bersma R. J., Thijs L. G., Hack C. E. Quantification of plasma factor XIIa-Cl(-)-inhibitor and kallikrein-Cl(-)-inhibitor complexes in sepsis. Blood. 1988 Dec;72(6):1841–1848. [PubMed] [Google Scholar]
  24. Patrassi G. M., Sartori M. T., Lazzaro A. R., Viero M. L., Boscaro M., Girolami A. Factor XII activation after DDAVP. Thromb Res. 1990 Jun 1;58(5):531–532. doi: 10.1016/0049-3848(91)90259-y. [DOI] [PubMed] [Google Scholar]
  25. Prowse C. V., Farrugia A., Boulton F. E., Tucker J., Ludlam C. A., McLaren M., Belch J. J., Prentice C. R., Dawes J., MacGregor I. R. A comparative study using immunological and biological assay of the haemostatic responses to DDAVP infusion venous occlusion and exercise in normal men. Thromb Haemost. 1984 Feb 28;51(1):110–114. [PubMed] [Google Scholar]
  26. RATNOFF O. D., COLOPY J. E. A familial hemorrhagic trait associated with a deficiency of a clot-promoting fraction of plasma. J Clin Invest. 1955 Apr;34(4):602–613. doi: 10.1172/JCI103109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Smith D., Gilbert M., Owen W. G. Tissue plasminogen activator release in vivo in response to vasoactive agents. Blood. 1985 Oct;66(4):835–839. [PubMed] [Google Scholar]
  28. Verheijen J. H., Mullaart E., Chang G. T., Kluft C., Wijngaards G. A simple, sensitive spectrophotometric assay for extrinsic (tissue-type) plasminogen activator applicable to measurements in plasma. Thromb Haemost. 1982 Dec 27;48(3):266–269. [PubMed] [Google Scholar]
  29. de Agostini A., Lijnen H. R., Pixley R. A., Colman R. W., Schapira M. Inactivation of factor XII active fragment in normal plasma. Predominant role of C-1-inhibitor. J Clin Invest. 1984 Jun;73(6):1542–1549. doi: 10.1172/JCI111360. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES