Thromb Haemost 2007; 97(01): 119-123
DOI: 10.1160/TH06-03-0141
Cellular Proteolysis and Oncology
Schattauer GmbH

Tissue factor-positive microparticles: Cellular origin and association with coagulation activation in patients with colorectal cancer

Gregor Hron
1   Departments of Internal Medicine I and
,
Marietta Kollars
1   Departments of Internal Medicine I and
,
Heinz Weber
1   Departments of Internal Medicine I and
,
Verena Sagaster
1   Departments of Internal Medicine I and
,
Peter Quehenberger
2   Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria
,
Sabine Eichinger
1   Departments of Internal Medicine I and
,
Paul A. Kyrle
1   Departments of Internal Medicine I and
,
Ansgar Weltermann
1   Departments of Internal Medicine I and
› Author Affiliations
Financial support: The study was supported by a grant (no. 10978) of the Jubiläumsfonds of the Österreichische Nationalbank.
Further Information

Publication History

Received 07 March 2006

Accepted after resubmission 14 November 2006

Publication Date:
28 November 2017 (online)

Summary

The pathogenesis of hypercoagulability in cancer is not entirely understood. We hypothesized that in cancer patients circulating tissue factor-positive microparticles (TF+ MPs) are increased and associated with hemostatic system activation. In 20 patients with advanced colorectal cancer and in 20 age- and sex-matched controls, number and cellular origin of TF+ MPs were determined in plasma by flow cytometry. D-dimer was determined as an indicator of hemostatic system activation. Compared to controls, the median (interquartile range) number of TF+ MPs was two-fold higher in cancer patients: 25.9 (15.4 – 42.0) × 103 /ml plasma versus 13.1 (11.9 – 19.7) × 103 /ml plasma, p = 0.007. This was mainly due to a higher amount of TF+ MPs from platelets (13.4 [5.0 – 17.4] × 103 /ml plasma vs. 5.8 [4.5 – 7.5] × 103 /ml plasma, p = 0.017). TF+ MPs correlated with D-dimer (ρ = 0.48, p = 0.002). High levels of TF+ MPs in cancer patients and their correlation with D-dimer suggest that TF+ MPs might be involved in hemostasis activation in cancer patients.

 
  • References

  • 1 Heit JA, Silverstein MD, Mohr DN. et al Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160: 809-15.
  • 2 Baron JA, Gridley G, Weiderpass E. et al Venous thromboembolism and cancer. Lancet 1998; 351: 1077-80.
  • 3 Sorensen HT, Mellemkjaer L, Olsen JH. et al Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000; 343: 1846-50.
  • 4 Sallah S, Husain A, Sigounas V. et al Plasma coagulation markers in patients with solid tumors and venous thromboembolic disease receiving oral anticoagulation therapy. Clin Cancer Res 2004; 10: 7238-43.
  • 5 Oya M, Akiyama Y, Okuyama T. et al High preoperative plasma D-dimer level is associated with advanced tumor stage and short survival after curative resection in patients with colorectal cancer. Jpn J Clin Oncol 2001; 31: 388-94.
  • 6 Iversen LH, Okholm M, Thorlacius-Ussing O. Preand postoperative state of coagulation and fibrinolysis in plasma of patients with benign and malignant colorectal disease – a preliminary study. Thromb Haemost 1996; 76: 523-8.
  • 7 Callander NS, Varki N, Rao LV. Immunohistochemical identification of tissue factor in solid tumors. Cancer 1992; 70: 1194-201.
  • 8 Nakasaki T, Wada H, Shigemori C. et al Expression of tissue factor and vascular endothelial growth factor is associated with angiogenesis in colorectal cancer. Am J Hematol 2002; 69: 247-54.
  • 9 Boccaccio C, Sabatino G, Medico E. et al The MET oncogene drives a genetic programme linking cancer to haemostasis. Nature 2005; 434: 396-400.
  • 10 Bogdanov VY, Balasubramanian V, Hathcock J. et al Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein. Nat Med 2003; 9: 458-62.
  • 11 Rauch U, Antoniak S, Boots M. et al Association of tissue-factor upregulation in squamous-cell carcinoma of the lung with increased tissue factor in circulating blood. Lancet Oncol 2005; 6: 254
  • 12 Diamant M, Tushuizen ME, Sturk A. et al Cellular microparticles: new players in the field of vascular disease?. Eur J Clin Invest 2004; 34: 392-401.
  • 13 Biro E, Sturk-Maquelin KN, Vogel GM. et al Human cell-derived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner. J Thromb Haemost 2003; 1: 2561-8.
  • 14 Chou J, Mackman N, Merrill-Skoloff G. et al Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation. Blood 2004; 104: 3190-7.
  • 15 Combes V, Simon AC, Grau GE. et al In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. J Clin Invest 1999; 104: 93-102.
  • 16 Chirinos JA, Heresi GA, Velasquez H. et al Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism. J Am Coll Cardiol 2005; 45: 1467-71.
  • 17 Rauch U, Bonderman D, Bohrmann B. et al Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor. Blood 2000; 96: 170-5.
  • 18 Yu JL, May L, Lhotak V. et al Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis. Blood 2005; 105: 1734-41.
  • 19 Seto S, Onodera H, Kaido T. et al Tissue factor expression in human colorectal carcinoma: correlation with hepatic metastasis and impact on prognosis. Cancer 2000; 88: 295-301.
  • 20 Haas SL, Jesnowski R, Steiner M. et al Expression of tissue factor in pancreatic adenocarcinoma is associated with activation of coagulation. World J Gastroenterol 2006; 12: 4843-9.
  • 21 Yu JL, Rak JW. Shedding of tissue factor (TF)-containing microparticles rather than alternatively spliced TF is the main source of TF activity released from human cancer cells. J Thromb Haemost 2004; 2: 2065-7.
  • 22 Antal-Szalmas P, Strijp JA, Weersink AJ. et al Quantitation of surface CD14 on human monocytes and neutrophils. J Leukoc Biol 1997; 61: 721-8.
  • 23 Østerud B.. Tissue factor in neutrophils: no J Thromb Haemost. 2004; 2: 218-20.
  • 24 Cosmi B, Legnani C, Cini M. et al The role of D-dimer and residual venous obstruction in recurrence of venous thromboembolism after anticoagulation withdrawal in cancer patients. Haematologica 2005; 90: 713-15.
  • 25 Berckmans RJ, Neiuwland R, Boing AN. et al Cellderived microparticles circulate in healthy humans and support low grade thrombin generation. Thromb Haemost 2001; 85: 639-46.
  • 26 Bach RR. Tissue factor encryption. Arterioscler Thromb Vasc Biol 2006; 26: 456-61.
  • 27 Rickles FR, Falanga A. Molecular basis for the relationship between thrombosis and cancer. Thromb Res 2001; 102: V215-24.
  • 28 Rickles FR, Patierno S, Fernandez PM. Tissue factor, thrombin, and cancer. Chest 2003; 124: 58S-68S.