Cancer-associated pathways and biomarkers of venous thrombosis

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

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.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Humans
  • Metabolic Networks and Pathways*
  • Neoplasms / complications*
  • Neoplasms / metabolism
  • Venous Thrombosis / diagnosis
  • Venous Thrombosis / etiology*
  • Venous Thrombosis / pathology

Substances

  • Biomarkers