| Title: | Venous thrombosis and cancer: from mouse models to clinical trials |
| Author(s): | Hisada Y; Geddings JE; Ay C; Mackman N; |
| Address: | "Division of Hematology and Oncology, Department of Medicine, Thrombosis and Hemostasis Program, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. K.G. Jensen Thrombosis Research and Expertise Center, University of Tromso, Tromso, Norway. Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Department of Medicine I, Medical University of Vienna, Vienna, Austria" |
| ISSN/ISBN: | 1538-7836 (Electronic) 1538-7933 (Print) 1538-7836 (Linking) |
| Abstract: | "Cancer patients have a ~4 fold increased risk of venous thromboembolism (VTE) compared with the general population and this is associated with significant morbidity and mortality. This review summarizes our current knowledge of VTE and cancer, from mouse models to clinical studies. Notably, the risk of VTE varies depending on the type and stage of cancer. For instance, pancreatic and brain cancer patients have a higher risk of VTE than breast and prostate cancer patients. Moreover, patients with metastatic disease have a higher risk than those with localized tumors. Tumor-derived procoagulant factors and growth factors may directly and indirectly enhance VTE. For example, increased levels of circulating tumor-derived, tissue factor-positive microvesicles may trigger VTE. In a mouse model of ovarian cancer, tumor-derived IL-6 and hepatic thrombopoietin have been linked to increased platelet production and thrombosis. In addition, mouse models of mammary and lung cancer showed that tumor-derived granulocyte colony-stimulating factor causes neutrophilia and activation of neutrophils. Activated neutrophils can release neutrophil extracellular traps (NETs) that enhance thrombosis. Cell-free DNA in the blood derived from cancer cells, NETs and treatment with cytotoxic drugs can activate the clotting cascade. These studies suggest that there are multiple mechanisms for VTE in patients with different types of cancer. Preventing and treating VTE in cancer patients is challenging; the current recommendations are to use low-molecular-weight heparin. Understanding the underlying mechanisms may allow the development of new therapies to safely prevent VTE in cancer patients" |
| Keywords: | "Animals Anticoagulants/therapeutic use *Blood Coagulation/drug effects Disease Models, Animal Fibrinolytic Agents/therapeutic use Humans Mice Neoplasms/blood/*complications/pathology Prognosis Risk Assessment Risk Factors Venous Thrombosis/blood/drug ther;" |
| Notes: | "MedlineHisada, Y Geddings, J E Ay, C Mackman, N eng F30HL117546/HL/NHLBI NIH HHS/ F30 HL117546/HL/NHLBI NIH HHS/ T32 HL007149/HL/NHLBI NIH HHS/ R01 HL095096/HL/NHLBI NIH HHS/ HL095096/HL/NHLBI NIH HHS/ Research Support, N.I.H., Extramural Review England 2015/05/20 J Thromb Haemost. 2015 Aug; 13(8):1372-82. doi: 10.1111/jth.13009. Epub 2015 Jun 26" |
