An official website of the United States government
The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before
sharing sensitive information, make sure you’re on a federal
government site.
The site is secure.
The https:// ensures that you are connecting to the
official website and that any information you provide is encrypted
and transmitted securely.
Cancer-associated thrombosis is a leading cause of non-cancer death in cancer patients and is comprised of both arterial and venous thromboembolism (VTE). There are multiple risk factors for developing VTE, including cancer type, stage, treatment, and other medical comorbidities, which suggests that the etiology of thrombosis is multifactorial. While cancer-associated thrombosis can be treated with anticoagulation, benefits of therapy must be balanced with the increased bleeding risks seen in patients with cancer. Although risk models exist for primary and recurrent VTE, additional predictors are needed to improve model performance and discrimination of high-risk patients. This review will outline the diverse mechanisms driving thrombosis in cancer patients, as well as provide an overview of biomarkers studied in thrombosis risk and important considerations when selecting candidate biomarkers.
Figure 1.. Graphical summary of key mechanisms driving cancer-associated thrombosis.
Interleukin-8 (IL-8), tumor necrosis factor-α…
Figure 1.. Graphical summary of key mechanisms driving cancer-associated thrombosis.
Interleukin-8 (IL-8), tumor necrosis factor-α (TNF- α), and granulocyte-colony stimulating factor (G-CSF) stimulate neutrophils to form neutrophil extracellular traps (NETs) containing cell free DNA (cfDNA) and citrullinated histone H3 (H3Cit). Extracellular vesicles (EVs), derived from tumor or host cells, express negatively charged phosphatidylserine (PS) which bind histones in NETs. EVs also express tissue factor (TF) which binds factor VIIa (FVIIa) to initiate the extrinsic pathway of coagulation and generate thrombin. Tumor cells can also secrete exosomes expressing polyphosphate (polyP) to activate the contact pathway. Similarly, platelets can express polyP to initiate contact pathway activation, as well as interact with cfDNA and histones present in NETs for thrombin and thrombus formation. Podoplanin-expressing activated endothelial cells can bind C-type lectin-like receptor 2 (CLEC-2) on platelets to induce platelet activation and aggregation. Inhibitory microRNAs (miRNAs) can be secreted extracellularly in a protein- or EV-bound form. Platelets and other host cells can take up miRNAs which regulate gene expression of coagulation factors and re-secrete miRNAs into plasma. FXIIa, factor XIIa; RBC, red blood cell.
Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007;5(3):632–634. doi:10.1111/j.1538-7836.2007.02374.x
-
DOI
-
PubMed
Heit JA, Silverstein MD, Mohr DN, Petterson TM, O’Fallon WM, Melton LJ. Risk Factors for Deep Vein Thrombosis and Pulmonary Embolism: A Population-Based Case-Control Study. Arch Intern Med. 2000;160(6):809–815. doi:10.1001/archinte.160.6.809
-
DOI
-
PubMed
Blom JW, Doggen CJM, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005;293(6):715–722. doi:10.1001/jama.293.6.715
-
DOI
-
PubMed
Grilz E, Königsbrügge O, Posch F, et al. Frequency, risk factors, and impact on mortality of arterial thromboembolism in patients with cancer. Haematologica. 2018;103(9):1549–1556. doi:10.3324/haematol.2018.192419
-
DOI
-
PMC
-
PubMed
Navi BB, Reiner AS, Kamel H, et al. Risk of Arterial Thromboembolism in Patients With Cancer. Journal of the American College of Cardiology. 2017;70(8):926–938. doi:10.1016/j.jacc.2017.06.047
-
DOI
-
PMC
-
PubMed
