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Thrombin Generation and Cancer: Contributors and Consequences

Authors
  • Reddel, Caroline J.1
  • Tan, Chuen Wen1, 2
  • Chen, Vivien M.1, 3
  • 1 (C.W.T.)
  • 2 Department of Haematology, Singapore General Hospital, Singapore 169608, Singapore
  • 3 Department of Haematology, Concord Hospital, Concord 2139, Australia
Type
Published Article
Journal
Cancers
Publisher
MDPI AG
Publication Date
Jan 16, 2019
Volume
11
Issue
1
Identifiers
DOI: 10.3390/cancers11010100
PMID: 30654498
PMCID: PMC6356447
Source
PubMed Central
Keywords
License
Green

Abstract

The high occurrence of cancer-associated thrombosis is associated with elevated thrombin generation. Tumour cells increase the potential for thrombin generation both directly, through the expression and release of procoagulant factors, and indirectly, through signals that activate other cell types (including platelets, leukocytes and erythrocytes). Furthermore, cancer treatments can worsen these effects. Coagulation factors, including tissue factor, and inhibitors of coagulation are altered and extracellular vesicles (EVs), which can promote and support thrombin generation, are released by tumour and other cells. Some phosphatidylserine-expressing platelet subsets and platelet-derived EVs provide the surface required for the assembly of coagulation factors essential for thrombin generation in vivo. This review will explore the causes of increased thrombin production in cancer, and the availability and utility of tests and biomarkers. Increased thrombin production not only increases blood coagulation, but also promotes tumour growth and metastasis and as a consequence, thrombin and its contributors present opportunities for treatment of cancer-associated thrombosis and cancer itself.

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