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Thrombin Generation and Cancer: Contributors and Consequences.

Caroline J Reddel1, Chuen Wen Tan2,3, Vivien M Chen4,5

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Cancer-associated thrombosis involves increased thrombin generation due to tumor cells and treatments. Thrombin also fuels cancer growth, offering therapeutic targets for both thrombosis and cancer.

Keywords:
cancerextracellular vesiclesneutrophil extracellular trapsplateletsprocoagulant plateletsthrombin generationthrombosis

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Area of Science:

  • Hematology
  • Oncology
  • Biochemistry

Background:

  • Cancer-associated thrombosis (CAT) is frequent, linked to elevated thrombin generation.
  • Tumor cells directly and indirectly promote thrombin generation via procoagulant factors and cell activation.
  • Cancer treatments can exacerbate these prothrombotic effects.

Purpose of the Study:

  • To review the mechanisms driving increased thrombin production in cancer.
  • To explore current and potential diagnostic tests and biomarkers for CAT.
  • To discuss therapeutic opportunities targeting thrombin in cancer.

Main Methods:

  • Literature review of studies on cancer, thrombosis, and coagulation.
  • Analysis of direct and indirect mechanisms of thrombin generation in cancer.
  • Evaluation of diagnostic and therapeutic strategies related to thrombin.

Main Results:

  • Tumor cells, activated platelets, leukocytes, erythrocytes, and extracellular vesicles (EVs) contribute to thrombin generation.
  • Phosphatidylserine-expressing platelets and platelet-derived EVs provide crucial surfaces for coagulation factor assembly.
  • Altered coagulation factors and inhibitors, alongside EVs, facilitate thrombin generation in cancer.

Conclusions:

  • Elevated thrombin generation is a key factor in cancer-associated thrombosis.
  • Thrombin contributes to tumor progression and metastasis, not just coagulation.
  • Targeting thrombin and its related pathways presents dual therapeutic potential for cancer and thrombosis.