Thrombosis Research
Volume 121, Issue 2 , Pages 145-151 , 2007

Venous thromboembolism in carriers of the Factor V Leiden mutation and in patients without known thrombophilic risk factor; prediction of recurrence and APC–PCI complex concentration and/or soluble thrombomodulin antigen and activity

  • Karin Strandberg

      Affiliations

    • Department of Clinical Chemistry, Lund University, Malmö University Hospital, SE-205 02 Malmö, Sweden
    • Corresponding Author InformationCorresponding author. Tel.: +46 40 33 1459; fax: +46 40 336286.
  • ,
  • Peter J. Svensson

      Affiliations

    • Department of Coagulation Disorders, Lund University, Malmö University Hospital, Sweden
  • ,
  • Ann-Kristin Öhlin

      Affiliations

    • Department of Clinical Chemistry, Lund University, Lund University Hospital, Sweden

Received 19 November 2006 ,Revised 19 February 2007 ,Accepted 27 March 2007.

References 

  1. Toschi V, Gallo R, Lettino M, Fallon J, Gertz S, Fernandez-Ortiz A, et al. Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. Circulation. 1997;95:594–599
  2. Dahlbäck B. Blood coagulation and its regulation by anticoagulant pathways: genetic pathogenesis of bleeding and thrombotic diseases. J Int Med Res. 2005;257:209–223
  3. Stenflo J, Dahlbäck B. Vitamin K-dependent proteins in blood coagulation. In:  Stamatopolous G,  Majerus PW,  Perlmutter RM,  Varmus H editor. The molecular basis of blood coagulation. Third ed. W.B. Saunders; 2001;p. 579–613
  4. Esmon CT. The endothelial protein C receptor. Thromb Haemost. 2000;83:639–643
  5. Suzuki K, Deyashiki Y, Nishioka J, Toma K. Protein C inhibitor: structure and function. Thromb Haemost. 1989;61:337–342
  6. Huntington JA, Kjellberg M, Stenflo J. Crystal structure of protein C inhibitor provides insights into hormone binding and heparin activation. Structure. 2003;11:205–215
  7. Marlar RA, Kressin DC, Madden RM. Contribution of plasma proteinase inhibitors to the regulation of activated protein C in plasma. Thromb Haemost. 1993;69:16–20
  8. Scully MF, Toh CH, Hoogendoorn H, Manuel RP, Nesheim ME, Solymoss S, et al. Activation of protein C and its distribution between its inhibitors, protein C inhibitor, α1-antitrypsin and α2-macroblobulin in patients with disseminated intravascular coagulation. Thromb Haemost. 1993;69:448–453
  9. Espana F, Gruber A, Heeb MJ, Hansson SR, Harker LA, Griffin JH. In vivo and in vitro complexes of activated protein C with two inhibitors in baboons. Blood. 1991;77:1754–1760
  10. Laurell M, Stenflo J, Carlsson TH. Turnover of I-protein C inhibitor and I-alfa-1-antritrypsin and their complexes with activated protein C. Blood. 1990;76:2290–2295
  11. Strandberg K, Bhiladvala P, Holm J, Stenflo J. A new method to measure plasma levels of activated protein C in complex with protein C inhibitor in patients with acute coronary syndromes. Blood Coagul Fibrinol. 2001;12:503–510
  12. Strandberg K, Astermark J, Björgell O, Becker C, Nilsson PE, Stenflo J. Complexes between activated protein C and protein C inhibitor measured with a new method: comparison of performance with other markers of hypercoagulability in the diagnosis of deep vein thrombosis. Thromb Haemost. 2001;86:1400–1408
  13. Tanigawa M, Wada H, Minamikawa K, Wakita Y, Nagaya A, Mori T, et al. Decreased protein C inhibitor after percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction. Am J Hematol. 1999;49:1–5
  14. Espana F, Vicente V, Tabernero D, Sharrer I, Griffin JH. Determination of plasma protein C inhibitor and of two activated protein C inhibitor complexes in normals and in patients with intravascular coagulation and thrombotic disease. Thromb Res. 1990;59:593–608
  15. Minamikawa K, Wada H, Wakita Y, Ohiwa M, Tanigawa M, Deguchi J, et al. Increased activated protein C–protein C inhibitor complex levels in patients with pulmonary embolism. Thromb Haemost. 1994;71:192–194
  16. Strandberg K, Kjellberg M, Erb EM, Persson U, Mosher DF, Villoutreix BO, et al. Activated protein C–protein C inhibitor Complex formation: characterisation of a neoepitope provides evidence for extensive insertion of a reactive center loop. Biochemistry. 2000;39:15713–15720
  17. Strandberg K, Kjellberg M, Knebel R, Lilja H, Stenflo J. A sensitive immunochemical assay for measuring the concentration of the activated protein C–protein C inhibitor complex in plasma. Thromb Haemost. 2001;86:604–610
  18. Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C. PNAS. 1993;90:1004–1008
  19. Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, De Ronde H, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature. 1994;369:64–67
  20. Strandberg K, Stenflo J, Nilsson C, Svensson PJ. APC–PCI concentration is higher in patients with previous venous thromboembolism with Factor V Leiden. J Thromb Haemost. 2005;3:2578–2601
  21. Takano S, Kimura S, Ohdama S, Aoki N. Plasma thrombomodulin in health and diseases. Blood. 1990;76:2024–2029
  22. Ishii H, Uchiyama H, Kazama M. Soluble thrombomodulin antigen in conditioned medium is increased by damage of endothelial cells. Thromb Haemost. 1991;65:618–623
  23. Boehme MW, Galle P, Stremmel W. Kinetics of thrombomodulin release and endothelial cell injury by neutrophil-derived proteases and oxygen radicals. Immunology. 2002;107:340–349
  24. Salomaa V, Matei C, Aleksic N, Sansores-Garcia L, Folsom AR, Juneja H, et al. Soluble thrombomodulin as a predictor of incident coronary heart disease and symptomless carotid artery atherosclerosis in the Atherosclerosis Risk in Communities (ARIC) Study: a case-cohort study. Lancet. 1999;353:1729–1734
  25. Konstantoulas CJ, Öhlin A-K, Humphries SE, Goodall AH, Toh C-H, Mather H, et al. measurements of soluble thrombomodulin activity and antigen: factors contributing to variance and potential for identification of protein variants. Thromb Haemost. 2007;97:161–164
  26. Öhlin AK, Larsson K, Hansson M. Soluble thrombomodulin activity and soluble thrombomodulin antigen in plasma. J Thromb Haemost. 2005;3:976–982
  27. Öhlin AK, Morser J, Ohlin H. Soluble thrombomodulin antigen in plasma is increased in patients with acute myocardial infarction treated with thrombolytic therapy. Thromb Res. 1996;82:313–322
  28. Strandberg K, Svensson A, Stenflo J. Stabilyte tubes that contain strongly acidic citrate prevents in vitro complex formation between activated protein C and protein C inhibitor. Thromb Haemost. 2003;89:947–949
  29. Faioni EM, Franchi F, Asti D, Mannucci PM. Activation of the protein C pathway in hereditary thrombophilia. Thromb Haemost. 1998;80:557–560
  30. Espana F, Vaya A, Mira Y, Medina P, Estelles A, Villa P, et al. Low level of circulating activated protein C is a risk factor for venous thromboembolism. Thromb Haemost. 2001;86:1368–1373
  31. Hron G, Kollars M, Binder BR, Eichinger S, Kyrle PA. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA. 2006;296:397–402
  32. Nowak-Gottl U, Vielhaber H. Elevated levels of soluble thrombomodulin in plasma from children with Arg 506 to Gln mutation in the factor V gene. Eur J Haematol. 1997;58:51–55
  33. Aleksic N, Folsom AR, Cushman M, Heckbert SR, Tsai MY, Wu KK. Prospective study of the A455V polymorphism in the thrombomodulin gene, plasma thrombomodulin, and incidence of venous thromboembolism: the LITE study. J Thromb Haemost. 2003;1:88–94
  34. Shrivastava S, Ridker PM, Glynn RJ, Goldhaber SZ, Moll S, Bounameaux H, et al. d-dimer, factor VIII coagulant activity, low-intensity warfarin and the risk of recurrent venous thromboembolism. J Thromb Haemost. 2006;4:1208–1214

PII: S0049-3848(07)00122-3

doi: 10.1016/j.thromres.2007.03.020

Thrombosis Research
Volume 121, Issue 2 , Pages 145-151 , 2007