What is the role of thrombin-activatable fibrinolytic inhibitor in the pathophysiology of factor XIII (FXIII) deficiency?

Updated: Aug 01, 2019
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Perumal Thiagarajan, MD  more...
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Thrombin-activatable fibrinolytic inhibitor (TAFI), a single-chain carboxypeptidase B–like zymogen, is activated by thrombin to become activated TAFI (TAFIa). [64] The importance of TAFIa in fibrinolysis is emphasized by the fact that the conversion of only 1% of the zymogen to TAFIa is sufficient to suppress fibrinolysis by approximately 60%.

TAFIa suppresses fibrinolysis by removing C-terminal lysine and arginine residues exposed in the partially degraded fibrin clot produced by plasmin. Removal of C-terminal lysine residues from fibrin reduces the rate of plasminogen activation by a number of mechanisms, attenuating fibrinolysis. This effect is counterbalanced in normal plasma by activation of protein C, which has profibrinolytic properties because of its ability to suppress thrombin generation via its major effect of degrading activated factor V (FVa), and to a lesser extent, activated factor VIII (FVIIIa). [64, 65, 66]

As illustrated in the chart below, a delicate balance usually exists between thrombus formation and thrombus resolution; thrombin secures survival of the thrombus created by its action on fibrinogen by activating TAFI, thereby inhibiting fibrinolysis. Cross-linking of fibrin induced by FXIIIa (activated by thrombin) renders the clot insoluble. FXIII deficiency results in absence of cross-linked fibrin, leading to premature lysis of the clot by the fibrinolytic system; adverse consequences result, including bleeding. Theoretically, a deficiency of TAFI leading to decreased suppression of fibrinolysis (enhanced clot lysis) can potentiate bleeding resulting from FXIII deficiency (also associated with enhanced clot lysis). Note the image below.

Postulated interaction between factor XIII and thr Postulated interaction between factor XIII and thrombin-activatable fibrinolytic inhibitor.

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