Bleeding Risks With Cancer

Vascular Etiology

The tumor microenvironment of many malignancies is rich with angiogenesis-stimulating growth factors; the most well-known is vascular endothelial growth factor (VEGF). The neoangiogenesis are typically unorganized and structurally dissimilar to the nonneoplastic vasculature and are more prone to bleeding. Malignant cells can also directly invade the vasculature, such as with lymphomatous involvement of the gastrointestinal (GI) tract leading to hematochezia. Bleeding may also occur within the body of the tumor, such as in hepatocellular carcinoma. Agents targeting angiogenesis have emerged and are in widespread use in both solid and hematologic malignancies, which can affect vessel and cause bleeding. VEGF inhibitors have been shown to cause predisposition to thrombosis and bleeding and after inhibition of VEGF signaling, have shown multiplicity of actions on vascular walls and interaction on the coagulation system. It is thought that inhibition of VEGF diminishes the regenerative capacity of endothelial cells and cause defects that expose procoagulant phospholipids on the luminal plasma membrane or underlying matrix, leading to thrombosis or hemorrhage. However, endothelial cell defects alone are unlikely to explain life-threatening hemorrhage in patients on anti-VEGF therapy and likely multifactorial with the complex interaction of weakening of the wall of major vessels by tumor erosion, necrosis, cavitation, and other concurrent pathological conditions are likely to play a central role. Other agents targeting the VEGF pathway such as sorafenib and sunitinib have also been linked to an increased incidence in bleeding complications.