Cancer-associated pathways and biomarkers of venous thrombosis

Yohei Hisada and Nigel Mackman

Article Figures & Data


  • Figure 1.

    Neutrophilia increases thrombosis in lung cancer. Tumor-derived G-CSF leads to increased levels of neutrophils, and these neutrophils release NETs that increase thrombosis in patients with lung cancer. EC, endothelial cell.

  • Figure 2.

    Thrombocytosis increases thrombosis in ovarian cancer. Tumor-derived IL-6 stimulates hepatocytes to express thrombopoietin (TPO), which increases platelet production and enhances thrombosis in patients with ovarian cancer.

  • Figure 3.

    Tumor-derived TF+MVs trigger thrombosis in pancreatic cancer. Pancreatic tumor cells release TF+ MVs into the circulation that trigger thrombosis in patients with pancreatic cancer.

  • Figure 4.

    Tumor-derived, PDPN+MVs trigger thrombosis in brain cancer. Brain tumor cells may release PDPN+ MVs that activate circulating platelets and increase thrombosis in patients with brain cancer.


  • Table 1.

    Proposed pathways of venous thrombosis in different types of cancer

    Tumor typeProposed primary pathwayReference
    Lung and colorectalLeukocytosis13, 19-24
    LungNeutrophilia and NETs27-29
    OvarianThrombocytosis6, 43-45, 52
    PancreaticTF+ MVs72, 73, 78, 80, 81
    BrainPDPN+ MVs105, 106
  • Table 2.

    Mouse studies on the role of tumor-derived TF+ MVs in cancer-associated thrombosis

    Tumor typeMouseTumor siteConclusionReference
    Human colorectal cancer cell linesSCIDSubcutaneousHuman TF antigen in plasma83
    Human pancreatic cancer cell line L3.6plNudeOrthotopicHuman TF MV activity and TAT in plasma84
    Mouse pancreatic cancer cell line Panc02 and lung cancer cell line LLC1C57BL/6JSubcutaneousIncreased thrombosis in mesenteric ferric chloride model57
    Human pancreatic cancer cell lines HPAF-II and HPACNudeSubcutaneous and orthotopicHuman TF antigen and MV activity and TAT in plasma67
    Mouse pancreatic cancer cell line Panc02C57BL/6JSubcutaneousIncreased thrombosis in IVC stenosis model85
    Human pancreatic cancer cell lines BxPc-3 and L3.6plNudeOrthotopicIncreased thrombosis in IVC stenosis model54
    Human pancreatic cancer cell line BxPc-3NudeOrthotopicHuman TF+ MVs increase thrombosis in IVC stasis model30
    • TAT, thrombin-antithrombin [complex].