Skip to main content
Log in

Tissue factor procoagulant activity of plasma microparticles in patients with cancer-associated disseminated intravascular coagulation

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Tissue factor (TF) expressed on sub-cellular membrane vesicles, so-called plasma microparticles (MPs), has recently emerged as a potential key player in intravascular coagulation activation in various disease states. In this report, we demonstrate significantly increased levels of TF-specific procoagulant activity (PCA) of plasma MPs in five patients presenting with overt disseminated intravascular coagulation (DIC) due to an underlying malignancy, including non-small-cell lung cancer (n = 1), melanoma (n = 1), prostate cancer (n = 2), and acute promyelocytic leukemia (n = 1). Clotting experiments on available tumor cell samples suggested that cancer cells were a potential source of circulating TF-positive MPs at least in three of the five patients. Furthermore, follow-up plasma samples from two surviving patients revealed that response of their malignancies to specific anti-cancer therapy was paralleled by resolution of overt DIC and a significant decline in MP-associated TF PCA. Levels of plasma TF antigen, as assessed by an enzyme-linked immunosorbent assay, were also increased at presentation albeit to a lesser extent compared to MP-associated TF PCA, likely due to insufficient solubilization of the phospholipid-incorporated full-length TF molecule by the detergent. In summary, our findings suggest that MP-associated TF PCA may play an important pathogenic role in the evolution of overt DIC in various types of malignancy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ahamed J, Versteeg HH, Kerver M, Chen VM, Mueller BM, Hogg PJ, Ruf W (2006) Disulfide isomerization switches tissue factor from coagulation to cell signalling. Proc Natl Acad Sci USA 103:13932–13937

    Article  PubMed  CAS  Google Scholar 

  2. Aras O, Shet A, Bach RR, Hysjulien JL, Shungaard A, Hebbel RP, Escolar G, Jilma B, Key NS (2004) Induction of microparticle- and cell-associated intravascular tissue factor in human endotoxemia. Blood 103:4545–4553

    Article  PubMed  CAS  Google Scholar 

  3. Bach RR (2006) Tissue factor encryption. Arterioscler Thromb Vasc Biol 26:456–461

    Article  PubMed  CAS  Google Scholar 

  4. Biró E, Sturk-Maquelin KN, Vogel GM, Meuleman DG, Smit MJ, Hack CE, Sturk A, Nieuwland R (2003) Human cell-derived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner. J Thromb Haemost 1:2561–2568

    Article  PubMed  Google Scholar 

  5. Biró E, Nieuwland R, Sturk A (2004) Measuring circulating cell-derived microparticles. J Thromb Haemost 2:1843–1844

    Article  Google Scholar 

  6. Bogdanov VY, Balasubramanian V, Hathcock J, Vele O, Lieb M, Nemerson Y (2003) Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein. Nat Med 9:458–462

    Article  PubMed  CAS  Google Scholar 

  7. Buller HR, van Doormaal FF, van Sluis GL, Kamphuisen PW (2007) Cancer and thrombosis: from molecular mechanisms to clinical presentations. J Thromb Haemost 5(Suppl 1):246–254

    Article  PubMed  CAS  Google Scholar 

  8. Butenas S, Bouchardm BA, Brummel-Ziedins KE, Parhami-Seren B, Mann KG (2005) Tissue factor activity in whole blood. Blood 105:2764–2770

    Article  PubMed  CAS  Google Scholar 

  9. De Cicco M (2004) The prothrombotic state in cancer: pathogenic mechanisms. Crit Rev Oncol Hematol 50:187–196

    Article  PubMed  Google Scholar 

  10. Del Conde I, Bharwani LD, Dietzen DJ, Pendurthi U, Thiagarajan P, López JA (2007) Microvesicle-associated tissue factor and Trousseau’s syndrome. J Thromb Haemost 5:70–74

    Article  PubMed  CAS  Google Scholar 

  11. Fernandes RS, Kirszberg C, Rumjanek VM, Monteiro RQ (2006) On the molecular mechanisms for the highly procoagulant pattern of C6 glioma cells. J Thromb Haemost 4:1546–1552

    Article  PubMed  CAS  Google Scholar 

  12. Heemskerk JW, Bevers EM, Lindhout T (2002) Platelet activation and coagulation. Thromb Haemost 88:186–193

    PubMed  CAS  Google Scholar 

  13. Hron G, Kollars M, Weber H, Sagaster V, Quehenberger P, Eichinger S, Kyrle PA, Weltermann A (2007) Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer. Thromb Haemost 97:119–123

    PubMed  CAS  Google Scholar 

  14. Kitchens CS (1998) Thrombotic storm: when thrombosis begets thrombosis. Am J Med 104:381–385

    Article  PubMed  CAS  Google Scholar 

  15. Langer F, Amirkhosravi A, Loges S, Meyer T, Eifrig B, Hossfeld DK, Fiedler W, Francis JL (2004) An in vitro study on the mechanisms of coagulation activation in acute myelogenous leukemia (AML): role of tissue factor regulation by cytotoxic drugs and GM-CSF. Thromb Haemost 92:1136–1146

    PubMed  CAS  Google Scholar 

  16. Levine MN, Lee AY, Kakkar AK (2003) From Trousseau to targeted therapy: new insights and innovations in thrombosis and cancer. J Thromb Haemost 1:1456–1463

    Article  PubMed  CAS  Google Scholar 

  17. Mackman N, Tilley RE, Key NS (2007) Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis. Arterioscler Thromb Vasc Biol 27:1687–1693

    Article  PubMed  CAS  Google Scholar 

  18. Mackman N (2007) Alternatively spliced tissue factor—one cut too many? Thromb Haemost 97:5–8

    PubMed  CAS  Google Scholar 

  19. Monroe DM, Key NS (2007) The tissue factor-factor VIIa complex: procoagulant activity, regulation and multitasking. J Thromb Haemost 5:1097–1105

    Article  PubMed  CAS  Google Scholar 

  20. Morel O, Toti F, Hugel B, Bakouboula B, Camoin-Jau L, Dignat-George F, Freyssinet JM (2006) Procoagulant microparticles: disrupting the vascular homeostasis equation? Arterioscler Thromb Vasc Biol 26:2594–2604

    Article  PubMed  CAS  Google Scholar 

  21. Rickles FR, Patierno S, Fernandez EM (2003) Tissue factor, thrombin, and cancer. Chest 124:58s–68s

    Article  PubMed  CAS  Google Scholar 

  22. Shet AS, Aras O, Gupta K, Hass MJ, Rausch DJ, Saba N, Koopmeiners L, Key NS, Hebbel RP (2003) Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes. Blood 102:2678–2683

    Article  PubMed  CAS  Google Scholar 

  23. Tallman MS, Abutalib SA, Altman JK (2007) The double hazard of thrombophilia and bleeding in acute promyelocytic leukemia. Semin Thromb Hemost 33:330–338

    Article  PubMed  Google Scholar 

  24. Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M (2001) Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 86:1327–1330

    PubMed  CAS  Google Scholar 

  25. Tesselaar ME, Romijn FP, Van Der Linden IK, Prins FA, Bertina RM, Osanto S (2007) Microparticle-associated tissue factor activity: a link between cancer and thrombosis? J Thromb Haemost 5:520–527

    Article  PubMed  CAS  Google Scholar 

  26. Toh CH, Hoots WK (2007) The scoring system of the Scientific and Standardization Committee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis: a 5-year overview. J Thromb Haemost 5:604–606

    Article  PubMed  CAS  Google Scholar 

  27. Varki A (2007) Trousseau’s syndrome: multiple definitions and multiple mechanisms. Blood 110:1723–1729

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Florian Langer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Langer, F., Spath, B., Haubold, K. et al. Tissue factor procoagulant activity of plasma microparticles in patients with cancer-associated disseminated intravascular coagulation. Ann Hematol 87, 451–457 (2008). https://doi.org/10.1007/s00277-008-0446-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-008-0446-3

Keywords

Navigation