Antithrombin III — MFDS Part 1 MCQ

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HardPhysiologyAntithrombin IIIMFDS Part 1

A plasma serine protease inhibitor (serpin) inactivates several activated coagulation proteases, including factors IXa, Xa, XIa and XIIa, and its activity is accelerated several thousand-fold by heparin. Which coagulation factor is its principal physiological target in the circulation?

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Correct answer: A — Factor IIa

The serpin described is antithrombin (formerly antithrombin III), the most important physiological inhibitor of the activated serine protease clotting factors and, above all, of factor IIa (thrombin); heparin binding accelerates this reaction dramatically, which underpins heparin anticoagulation. Factors VIIIa and Va are non-enzymatic cofactors, not serine proteases, and are inactivated by activated protein C with protein S, not by antithrombin. Von Willebrand factor is an adhesive glycoprotein and carrier for factor VIII, with no protease activity to inhibit. Tissue factor is a membrane receptor/cofactor for factor VIIa; the tissue factor–VIIa complex is regulated principally by tissue factor pathway inhibitor. Only factor IIa is therefore defensible.

Reference: Blajchman MA. An overview of the mechanism of action of antithrombin and its inherited deficiency states. Blood Coagulation & Fibrinolysis. 1994;5(Suppl 1):S5–11. https://pubmed.ncbi.nlm.nih.gov/8186357/