Download PDF
Thromb Haemost 2018; 118(01): 123-131
DOI: 10.1160/TH17-07-0548
Cellular Haemostasis and Platelets
Schattauer GmbH Stuttgart

Platelet Count, ADAMTS13 Activity, von Willebrand Factor Level and Survival in Patients with Colorectal Cancer: 5-Year Follow-up Study

Nóra Garam   *
,
Éva Maláti   *
,
György Sinkovits
,
Tímea Gombos
,
Attila Szederjesi
,
Loránd Barabás
,
László Gráf
,
Judit Kocsis
,
Zoltán Prohászka
Further Information

Publication History

10 August 2017

13 October 2017

Publication Date:
05 January 2018 (online)

Also available at
    Permissions and Reprints

Abstract

Distant metastasis is a major cause of colorectal cancer–related death, but the mechanism of tumour progression is not fully understood. There is growing evidence of an interaction between tumour cells and platelets which may influence tumour progression and metastasis formation. Quality and quantity of von Willebrand factor may regulate the interaction between tumour cells and platelets. Our aim was to measure the platelet count, von Willebrand factor antigen (VWF:Ag) levels and ADAMTS13 activity in a large (n = 232) cohort of colorectal cancer patients and to examine their relationships with the stage of the disease and 5-year survival without thrombotic complications using multivariable models. Significantly higher platelet counts (p = 0.005), VWF:Ag levels (p = 0.008) and decreased ADAMTS13 activity (p = 0.006) were observed in patients with metastatic disease. Results of the Kaplan–Meier analysis showed that lower platelet counts (p < 0.0001), lower VWF:Ag (p = 0.0008) levels and higher ADAMTS13 activity (p < 0.0001) were associated with better event-free survival. Finally, to investigate the association between overall event-free survival and the three study variables, multivariate Cox proportional hazard models were generated. All models were adjusted for age, gender and disease stage. Platelet count, ADAMTS13 activity or VWF:Ag level were incorporated and all of these variables turned out to be age-, gender- and stage-independent predictors of mortality (all hazard ratio >1.7, p < 0.05). In summary, this is the first observational study reporting association between higher mortality or thrombotic complications and increased platelet count, increased VWF:Ag levels and decreased ADAMTS13 activity in colorectal cancer.

Keywords

ADAMTS13 - platelet - von Willebrand factor - mortality - colorectal cancer

* Nóra Garam and Éva Maláti have equally contributed to this study.


Supplementary Material

 

  • References

  • 1 Vogelaar I, van Ballegooijen M, Schrag D. , et al. How much can current interventions reduce colorectal cancer mortality in the U.S.? Mortality projections for scenarios of risk-factor modification, screening, and treatment. Cancer 2006; 107 (07) 1624-1633
    CrossrefPubMedGoogle Scholar
  • 2 Hur K. MicroRNAs: promising biomarkers for diagnosis and therapeutic targets in human colorectal cancer metastasis. BMB Rep 2015; 48 (04) 217-222
    CrossrefPubMedGoogle Scholar
  • 3 Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin 2014; 64 (02) 104-117
    CrossrefPubMedGoogle Scholar
  • 4 Goubran HA, Stakiw J, Radosevic M, Burnouf T. Platelet-cancer interactions. Semin Thromb Hemost 2014; 40 (03) 296-305
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Tesfamariam B. Involvement of platelets in tumor cell metastasis. Pharmacol Ther 2016; 157: 112-119
    CrossrefPubMedGoogle Scholar
  • 6 Allensworth SK, Langstraat CL, Martin JR. , et al. Evaluating the prognostic significance of preoperative thrombocytosis in epithelial ovarian cancer. Gynecol Oncol 2013; 130 (03) 499-504
    CrossrefPubMedGoogle Scholar
  • 7 Kim KH, Park TY, Lee JY. , et al. Prognostic significance of initial platelet counts and fibrinogen level in advanced non-small cell lung cancer. J Korean Med Sci 2014; 29 (04) 507-511
    CrossrefPubMedGoogle Scholar
  • 8 Kim M, Chang H, Yang HC. , et al. Preoperative thrombocytosis is a significant unfavorable prognostic factor for patients with resectable non-small cell lung cancer. World J Surg Oncol 2014; 12: 37
    CrossrefPubMedGoogle Scholar
  • 9 Nozoe T, Iguchi T, Maeda T, Kohno M, Ezaki T. Simple criteria to predict prognosis in colorectal carcinoma based on lymphopenia and thrombocytosis. Mol Clin Oncol 2013; 1 (01) 171-174
    PubMedGoogle Scholar
  • 10 Sasaki K, Kawai K, Tsuno NH, Sunami E, Kitayama J. Impact of preoperative thrombocytosis on the survival of patients with primary colorectal cancer. World J Surg 2012; 36 (01) 192-200
    CrossrefPubMedGoogle Scholar
  • 11 Ishizuka M, Nagata H, Takagi K, Iwasaki Y, Kubota K. Preoperative thrombocytosis is associated with survival after surgery for colorectal cancer. J Surg Oncol 2012; 106 (07) 887-891
    CrossrefPubMedGoogle Scholar
  • 12 Monreal M, Fernandez-Llamazares J, Piñol M. , et al. Platelet count and survival in patients with colorectal cancer--a preliminary study. Thromb Haemost 1998; 79 (05) 916-918
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Kawai K, Kitayama J, Tsuno NH, Sunami E, Watanabe T. Thrombocytosis before pre-operative chemoradiotherapy predicts poor response and shorter local recurrence-free survival in rectal cancer. Int J Colorectal Dis 2013; 28 (04) 527-535
    CrossrefPubMedGoogle Scholar
  • 14 Wan S, Lai Y, Myers RE. , et al. Preoperative platelet count associates with survival and distant metastasis in surgically resected colorectal cancer patients. J Gastrointest Cancer 2013; 44 (03) 293-304
    CrossrefPubMedGoogle Scholar
  • 15 Stone RL, Nick AM, McNeish IA. , et al. Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med 2012; 366 (07) 610-618
    CrossrefPubMedGoogle Scholar
  • 16 Yang X, Sun HJ, Li ZR. , et al. Gastric cancer-associated enhancement of von Willebrand factor is regulated by vascular endothelial growth factor and related to disease severity. BMC Cancer 2015; 15: 80
    CrossrefPubMedGoogle Scholar
  • 17 Luo GP, Ni B, Yang X, Wu YZ. von Willebrand factor: more than a regulator of hemostasis and thrombosis. Acta Haematol 2012; 128 (03) 158-169
    CrossrefPubMedGoogle Scholar
  • 18 Lippok S, Radtke M, Obser T. , et al. Shear-induced unfolding and enzymatic cleavage of full-length VWF multimers. Biophys J 2016; 110 (03) 545-554
    CrossrefPubMedGoogle Scholar
  • 19 Mannucci PM, Karimi M, Mosalaei A, Canciani MT, Peyvandi F. Patients with localized and disseminated tumors have reduced but measurable levels of ADAMTS-13 (von Willebrand factor cleaving protease). Haematologica 2003; 88 (04) 454-458
    PubMedGoogle Scholar
  • 20 Francis KK, Kalyanam N, Terrell DR, Vesely SK, George JN. Disseminated malignancy misdiagnosed as thrombotic thrombocytopenic purpura: A report of 10 patients and a systematic review of published cases. Oncologist 2007; 12 (01) 11-19
    CrossrefPubMedGoogle Scholar
  • 21 Lechner K, Obermeier HL. Cancer-related microangiopathic hemolytic anemia: clinical and laboratory features in 168 reported cases. Medicine (Baltimore) 2012; 91 (04) 195-205
    CrossrefPubMedGoogle Scholar
  • 22 Oleksowicz L, Bhagwati N, DeLeon-Fernandez M. Deficient activity of von Willebrand's factor-cleaving protease in patients with disseminated malignancies. Cancer Res 1999; 59 (09) 2244-2250
    PubMedGoogle Scholar
  • 23 Elyamany G, Alzahrani AM, Bukhary E. Cancer-associated thrombosis: an overview. Clin Med Insights Oncol 2014; 8: 129-137
    PubMedGoogle Scholar
  • 24 Gombos T, Makó V, Cervenak L. , et al. Levels of von Willebrand factor antigen and von Willebrand factor cleaving protease (ADAMTS13) activity predict clinical events in chronic heart failure. Thromb Haemost 2009; 102 (03) 573-580
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Cejka J. Enzyme immunoassay for factor VIII-related antigen. Clin Chem 1982; 28 (06) 1356-1358
    PubMedGoogle Scholar
  • 26 Pimanda J, Hogg P. Control of von Willebrand factor multimer size and implications for disease. Blood Rev 2002; 16 (03) 185-192
    CrossrefPubMedGoogle Scholar
  • 27 Arya M, Anvari B, Romo GM. , et al. Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: studies using optical tweezers. Blood 2002; 99 (11) 3971-3977
    CrossrefPubMedGoogle Scholar
  • 28 Goubran HA, Kotb RR, Stakiw J, Emara ME, Burnouf T. Regulation of tumor growth and metastasis: the role of tumor microenvironment. Cancer Growth Metastasis 2014; 7: 9-18
    PubMedGoogle Scholar
  • 29 Wagner DD, Frenette PS. The vessel wall and its interactions. Blood 2008; 111 (11) 5271-5281
    CrossrefPubMedGoogle Scholar
  • 30 Terraube V, Marx I, Denis CV. Role of von Willebrand factor in tumor metastasis. Thromb Res 2007; 120 (Suppl. 02) S64-S70
    CrossrefPubMedGoogle Scholar
  • 31 Bauer AT, Suckau J, Frank K. , et al. von Willebrand factor fibers promote cancer-associated platelet aggregation in malignant melanoma of mice and humans. Blood 2015; 125 (20) 3153-3163
    CrossrefPubMedGoogle Scholar
  • 32 Wang WS, Lin JK, Lin TC. , et al. Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma. World J Gastroenterol 2005; 11 (14) 2166-2170
    CrossrefPubMedGoogle Scholar
  • 33 Zietek Z, Iwan-Zietek I, Paczulski R, Kotschy M, Wolski Z. von Willebrand factor antigen in blood plasma of patients with urinary bladder carcinoma. Thromb Res 1996; 83 (05) 399-402
    CrossrefPubMedGoogle Scholar
  • 34 Oleksowicz L, Dutcher JP, Deleon-Fernandez M, Paietta E, Etkind P. Human breast carcinoma cells synthesize a protein immunorelated to platelet glycoprotein-Ib alpha with different functional properties. J Lab Clin Med 1997; 129 (03) 337-346
    CrossrefPubMedGoogle Scholar
  • 35 Oleksowicz L, Dutcher JP, DeLeon-Fernandez M, Etkind P. A GPIb alpha-related protein is expressed by fresh human breast carcinoma tissue and is regulated by a PKC-sensitive mechanism. Exp Cell Res 1997; 237 (01) 110-117
    CrossrefPubMedGoogle Scholar
  • 36 Verheul HM, Hoekman K, Luykx-de Bakker S. , et al. Platelet: transporter of vascular endothelial growth factor. Clin Cancer Res 1997; 3 (12, Pt 1): 2187-2190
    PubMedGoogle Scholar