Cancer-associated pathways and biomarkers of venous thrombosis

Yohei Hisada and Nigel Mackman


Cancer patients have an increased risk of venous thromboembolism (VTE). In this review, we will summarize common and cancer type-specific pathways of VTE in cancer patients. Increased levels of leukocytes, platelets and tissue factor-positive (TF+) microvesicles are all potential factors that alone or in combination increase cancer-associated thrombosis. Lung and colorectal cancer patients 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 with pancreatic and brain cancer patients suggest that elevated levels of PAI-1 may contribute to VTE. Although elevated levels of TF+ microvesicles have been observed in patients with different types of cancer, an association between TF+ microvesicles and VTE has only been observed in pancreatic cancer. Podoplanin expression is associated with VTE in brain cancer patients and may activate platelets. Future studies should measure multiple biomarkers in each cancer type to determine if 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.

  • Submitted March 27, 2017.
  • Accepted August 2, 2017.