Schematic representation of the new insights in the role of FXIIa in fibrin clot formation. Activaton of FXII leads to the formation of 2 forms of activated FXII: α-FXIIa (2-chain molecule composed of a heavy chain and a light chain held together by a disulfide bond, the same molecular weight as FXII) and further proteolytic cleavage results in β-FXIIa (loss of the heavy chain). α-FXIIa can initiate thrombin formation via the intrinsic pathway of coagulation by activating FXI. FXII and α-FXIIa can both bind with the same affinity to fibrinogen and fibrin, and binding of α-FXIIa leads to a direct effect on fibrin structure.