*2.1.3. Defective fibrinolysis—hypofibrinolysis*

Tumor cells expressed on their cellular surface all proteins necessary for regulation of the fibrinolytic pathways. Deregulation in generating normal fibrinolytic activity was observed in patients with solid tumors and is a mechanism for the development of thrombotic tendency [45].

Plasminogen activator inhibitor-1 (PAI-1)—important regulator of plasminogen activity. PAI-1 is overexpressed in different types of tumors [21]. Genomic sequencing of hepatocytes expressing the MET oncogene demonstrated significantly increased expression of the gene for PAI-1 and COX-2 that corresponded with triple increase in levels of circulating plasma proteins [46].

Thrombin-activated fibrinolysis inhibitor (TAFI)—blocks the binding of plasminogen to fibrin. Reported elevated levels of TAFI in patients with cancer and thromboembolic events were compared to patients with acute venous thrombosis and normal controls [47, 48].

Proteinase inhibitor of fibrinolysis (α2-antiplasmin, α2-macroglobulin)—secreted in the tumor microenvironment/in high doses/in cancers with increased risk of venous thromboembolism [49]. Immunohistochemical studies demonstrate the expression of fibrinolytic inhibitors only in tumor cells, which could explain the absence of fibrinolytic activity in some tumors [50].
