January 2026 QQ Summary: Fibrinolysis

Our January 2026 QQ was a quiz that asked, “What fibrinolytic enzyme digests fibrin?” Here’s how our 34 respondents scored:

1. D-dimer: 0
2. Plasmin 28 (82%)
3. PAI-1: 2 (6%)
4. TAFI 0
5. TPA 4 (12%)

Congratulations on your successful answers. Here is a summary of fibrinolysis (figure), paraphrased from Walenga JM, Krum KN. Normal Hemostasis. In Keohane EM, Butina MM, Mirza KM, Walenga JM. Rodak’s Hematology: Clinical Principles and Applications, 7th Edition, 2025.

• Fibrinolysis is the systematic, accelerating hydrolysis of fibrin by plasmin. To localize fibrinolysis to the site of an injury where a clot has formed, fibrinolytic proteins become incorporated into the fibrin clot as it is forming. The clot-bound fibrinolytic process becomes activated several hours after fibrin polymerization. The key fibrinolysis activator, tissue plasminogen activator (TPA), is released from the endothelium. This converts nearby fibrin-bound plasminogen into the principal enzyme of the fibrinolytic system, plasmin, which digests fibrin, restoring normal blood flow during vascular repair.
• Plasminogen activator inhibitor-type 1 (PAI-1) inactivates TPA, thus preventing it from converting plasminogen to plasmin. PAI-1 is present in excess of the TPA concentration in plasma, and circulating TPA normally becomes bound to PAI-1. Only at times of endothelial activation, such as after trauma, does the level of TPA secretion exceed that of PAI-1 to initiate fibrinolysis.
• α2-Antiplasmin (AP) is the primary inhibitor of free plasmin. Free plasmin produced by activation of plasminogen can bind either to fibrin, where it is protected from AP, or to circulating AP, which rapidly and irreversibly inactivates the otherwise dangerous free plasmin.
• Thrombin-activatable fibrinolysis inhibitor (TAFI) is a plasma procarboxypeptidase synthesized in the liver. Activated TAFI functions as an antifibrinolytic enzyme. It inhibits fibrinolysis by preventing the binding of TPA and plasminogen to fibrin and blocking the formation of plasmin.