Direct and indirect mechanisms involved in cancer-associated thrombosis
| Target . | Cancer cell–derived factor to induce prothrombotic status . | Action . | |
|---|---|---|---|
| Coagulation cascade | Increased TF expression | Thrombin and fibrin generation Platelet activation by thrombin | |
| PAI-1 | Inhibited fibrinolysis | ||
| Platelets | ADP release | Platelet aggregation via P2Y1 and P2Y12 and adhesion to cancer cells | |
| Podoplanin | Platelet aggregation via CLEC-2 and adhesion to cancer cells | ||
| Other | Neutrophils | Any factors derived from cancer | NET generation and subsequent activation of platelets and FXII by NETs |
| Platelets and neutrophils | IL-6 (stimulate TPO generation in the liver), G-CSF secretion | Granulocytosis and thrombocytosis | |
| Mucins | Aggregation via P-selectin in platelets and L-selectin in neutrophils | ||
| Endothelial cells | Inflammatory cytokines | Prothrombotic change | |
| Target . | Cancer cell–derived factor to induce prothrombotic status . | Action . | |
|---|---|---|---|
| Coagulation cascade | Increased TF expression | Thrombin and fibrin generation Platelet activation by thrombin | |
| PAI-1 | Inhibited fibrinolysis | ||
| Platelets | ADP release | Platelet aggregation via P2Y1 and P2Y12 and adhesion to cancer cells | |
| Podoplanin | Platelet aggregation via CLEC-2 and adhesion to cancer cells | ||
| Other | Neutrophils | Any factors derived from cancer | NET generation and subsequent activation of platelets and FXII by NETs |
| Platelets and neutrophils | IL-6 (stimulate TPO generation in the liver), G-CSF secretion | Granulocytosis and thrombocytosis | |
| Mucins | Aggregation via P-selectin in platelets and L-selectin in neutrophils | ||
| Endothelial cells | Inflammatory cytokines | Prothrombotic change | |
ADP, adenosine 5′-diphosphate; CLEC-2, C-type lectin-like receptor 2; FXII, factor XII; G-CSF, granulocyte colony-stimulating factor; IL-6, interleukin 6; NET, neutrophil extracellular trap; PAI-1, plasminogen activator inhibitor 1; TF, tissue factor; TPO, thrombopoietin.