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Review
. 2017 Sep 28;130(13):1499-1506.
doi: 10.1182/blood-2017-03-743211. Epub 2017 Aug 14.

Cancer-associated pathways and biomarkers of venous thrombosis

Yohei Hisada  1   2 , Nigel Mackman  1
Affiliations
Review

Cancer-associated pathways and biomarkers of venous thrombosis

Yohei Hisada et al. Blood. .

Abstract

Cancer patients have an increased risk of venous thromboembolism (VTE). In this review, we summarize common and cancer type-specific pathways of VTE in cancer patients. Increased levels of leukocytes, platelets, and tissue factor-positive (TF+) microvesicles (MVs) are all potential factors that alone or in combination increase cancer-associated thrombosis. Patients with lung or colorectal cancer often exhibit leukocytosis. Neutrophils could increase VTE in cancer patients by releasing neutrophil extracellular traps whereas monocytes may express TF. Thrombocytosis is often observed in gastrointestinal, lung, breast, and ovarian cancer and this could decrease the threshold required for VTE. Soluble P-selectin has been identified as a biomarker of cancer-associated thrombosis in a general cancer population and may reflect activation of the endothelium. P-selectin expression by the endothelium may enhance VTE by increasing the recruitment of leukocytes. Studies in patients with pancreatic or brain cancer suggest that elevated levels of PAI-1 may contribute to VTE. Although elevated levels of TF+ MVs have been observed in patients with different types of cancer, an association between TF+ MVs and VTE has been observed only in pancreatic cancer. Podoplanin expression is associated with VTE in patients with brain cancer and may activate platelets. Future studies should measure multiple biomarkers in each cancer type to determine whether combinations of biomarkers can be used as predictors of VTE. A better understanding of the pathways that increase VTE in cancer patients may lead to the development of new therapies to reduce the morbidity and mortality associated with thrombosis.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Figure 1.
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.
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.
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.
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.
See this image and copyright information in PMC

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