Coagulation factor XI as a protector against heart failure: Diverse effects and potential threats

Factor (F) XI, a 160 kDa homodimeric serine protease synthesized in the liver, is activated by active FXII, which is generated by -kallikrein in a positive feedback loop and undergoes autoactivation on negatively charged molecules and surfaces, such as misfolded proteins, polyphosphates, and nucleic acids, including NETosis-associated chromatin (Figure 1) [1].Activated FXI (FXIa) catalyzes the conversion of FIX to its active form, along with FV and FVIII, and a partial inactivation of tissue factor pathway inhibitor, which amplifies thrombin generation and clot formation [2].Thrombin may reciprocally activate FXI, which is enhanced by platelet-derived polyphosphates, and FXI/FXIa can bind to platelets and endothelial cells [2].