Model of D dimer-initiated negative regulatory feedback loop of peri-cellular fibrinolysis. As a consequence of plasmin proteolysis of cross-linked fibrin, D dimer is generated and initiates a signal that results in AP-1–dependent induction of PAI-1 transcription using the −59 to −52 element. New PAI-1 protein is synthesized and, upon secretion, binds with high affinity to plasminogen activators, thereby blocking further activation of plasminogen to active plasmin. Upon loss of plasmin action, fibrinolysis ceases, allowing fibrin persistence and halting further generation of D dimer.