Factor V Leiden is resistant to direct inactivation by:
**Core Concept**
Factor V Leiden is a variant of the factor V gene that leads to thrombophilia, characterized by an increased risk of venous thrombosis. This mutation affects the **coagulation cascade**, specifically the inactivation of factor V by **activated protein C (APC)**. The **factor V Leiden mutation** results in a change at position 506 from arginine to glutamine, making factor V resistant to inactivation.
**Why the Correct Answer is Right**
The correct answer is related to the mechanism by which **activated protein C (APC)** inactivates factor V. Normally, APC cleaves and inactivates factor V, which is an essential step in regulating the coagulation pathway. However, the **Factor V Leiden mutation** makes factor V resistant to this inactivation by APC. This is because the mutation alters the cleavage site that APC recognizes, thereby reducing the ability of APC to inactivate factor V.
**Why Each Wrong Option is Incorrect**
**Option A:** This is incorrect because while tissue factor pathway inhibitor does play a role in coagulation, it is not directly related to the inactivation of factor V by APC.
**Option B:** Incorrect as protein S is a cofactor for APC but not the direct inactivator of factor V.
**Option D:** Incorrect because antithrombin is involved in the inactivation of other coagulation factors but not directly in the inactivation of factor V by APC.
**Clinical Pearl / High-Yield Fact**
A key point to remember is that Factor V Leiden is the most common inherited risk factor for **venous thromboembolism**, and its presence significantly increases the risk of deep vein thrombosis and pulmonary embolism, especially in individuals with other risk factors.
**Correct Answer:** D. Activated Protein C.