Cross-linkage between thrombin-activatable fibrinolysis inhibitor (TAFI) and fibrin is not necessary for TAFI function. (A) Activated factor XIII inhibitor (FXIIIaI; R283, an irreversible inhibitor against FXIIIa), at 1 mM, and/or activated TAFI inhibitor (TAFIaI), at 5 µM, were added to normal (n = 7) or FXIII-deficient plasma (n = 5), with or without washed normal platelets. Tissue-type plasminogen activator (tPA, 1.5 nM)-induced plasma clot lysis times were determined and are presented as the average ± SD. Significant differences were analyzed using Student t test (^#P < .05, ^##P < .01 vs control, ⁺P < .05, ⁺⁺P < .01 R283 vs R283 and TAFIaI). (B) Representative sequential high magnification (63× objective) images of Alexa Fluor 488-labeled fibrinogen (fbg-488, top, green), Alexa Fluor 568-labeled plasminogen (plg-568, second from top, red), and Alexa Fluor 647-labeled TAFI (TAFI-647, third from top, blue) in normal platelet-containing FXIII-deficient plasma. Clot lysis was initiated by the addition of tPA (2 nM).