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. Author manuscript; available in PMC: 2017 Jul 1.
Published in final edited form as: Arterioscler Thromb Vasc Biol. 2016 May 12;36(7):1316–1322. doi: 10.1161/ATVBAHA.116.306925

Figure 1. The Relationship of Factor XI to Thrombin Generation and Contact Activation.

Figure 1

Proteolytic reactions required for thrombin generation at an injury site are shown in the gray oval on the left, with each reaction indicated by a yellow arrow. The factor VIIa/tissue factor (TF) complex initiates thrombin generation by activating factors X and IX. Activated factor X (factor Xa) is responsible for cleaving prothrombin to form thrombin. Protease zymogens are indicated in black, and their active forms are indicated by a lower case “a”. Cofactors are shown as red ovals. Calcium (Ca2+) and phospholipid (PL) dependent reactions are indicated. Thrombin generated early in coagulation converts fXI to fXIa, which sustains thrombin production through factor IX activation (green arrows). Note that fXI activation does not require fXIIa, explaining why fXII deficiency does not cause bleeding. Proteolytic reactions involved in contact activation are shown in the gray oval on the right, with each reaction indicated by a black arrow. Artificial or abnormal surfaces facilitate fXII autoactivation. FXIIa converts prekallikrein (PK) to α-kallikrein, which activates additional fXII and cleaves high-molecular-weight kininogen (HK), liberating bradykinin (BK) and antimicrobial peptides (AMPs). Contact activation can promote thrombin generation through fXIIa-mediated activation of FXI [11,12]. There is evidence that fXIa, in turn, can activate fXII [13], although this is not a standard part of contact activation models. In plasma, PK and fXI circulate as complexes with HK, which may serve as a cofactor for PK and fXI activation. Activation of fXI by fXIIa is not required for hemostasis, but contributes to thrombosis in animal models. FXI is considered a component of contact activation (kallikrein-kinin) and thrombin generation in the scheme shown here, functioning as a bidirectional interface between the two systems. Hypothetically, activation of either system could activate the other through fXI conversion to fXIa. Image adapted from references 4 and 13.