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. 2020 Jan 17;30(2):101–102. doi: 10.1038/s41422-020-0275-z

Fig. 1. Transferrin regulates systemic blood coagulation.

Fig. 1

a The hemostatic and inhibitor systems in plasma. Lines in black represent activation pathways; lines in red represent inhibitory pathways. The blood coagulation system is activated in two ways: factor XIIa (XIIa) activates factor XI (XI) or tissue factor and factor VIIa (VIIa) activates factor IX (IX). High molecular weight kininogen (HK) and plasma kallikrein (PKa) activate factor XII (XII) to activated factor XII (XIIa). Both pathways lead to factor X activation (Xa). Xa along with factor V (V) catalyzes prothrombin (II) activation to thrombin (IIa), the main blood coagulation enzyme. Thrombin formation is regulated by three systems: (1) the tissue factor pathway inhibitor (TFPI) that regulates VII’s and tissue factor’s direct activation of X; (2) antithrombin that inhibits Xa, IIa, and every other blood coagulation enzyme (not shown); (3) activated protein C (APC) along with its cofactor, protein S, that inactivates VIIIa and Va forms of these cofactors to serve as cofactors for X and II activation, respectively. The present paper introduces another regulator to the blood coagulation system. Transferrin increases activity of factor XIIa (XIIa) and thrombin (IIa) by opening their catalytic sites. It also inhibits antithrombin by binding to its reactive center loop. b The major proteins of the blood coagulation system. Coagulation proteins: factor XII (XII), prekallikrein (PK), factor XI (XI), factor IX (IX), factor VII (VII), factor X (X), and prothrombin (II). Coagulation cofactors and substrates: high molecular weight kininogen (HK), factor VIII (VIII), factor V (V), fibrinogen, and protein S. Tissue factor was not included in this table. Fibrinolytic proteins: plasminogen, tissue plasminogen activator, urokinase plasminogen activator. Protease inhibitors: antithrombin, C1 inhibitor (inhibitor of factor XIIa, plasma kallikrein, factor XIa), α-2-antiplasmin, plasminogen activator inhibitor (PAI-1), and TFPI. The plasma concentration of transferrin is greater than the sum of all coagulation, cofactor/substrate, fibrinolytic, and protease inhibitors combined.