Which of the following coagulation factors is synthesized exclusively in the liver and requires vitamin K for its γ-carboxylation?

Question

Accepted Answer

C. Factor VII. ## Vitamin K-Dependent Coagulation Factors

**Key Point:** Vitamin K is an essential cofactor for the post-translational γ-carboxylation of glutamic acid residues in coagulation factors, enabling their calcium-dependent binding to phospholipid surfaces.

### The Vitamin K-Dependent Factors

**Mnemonic:** **PIVKA** — Proteins Induced by Vitamin K Absence (also remembered as **"II, VII, IX, X"** — the four main vitamin K-dependent factors)

| Factor | Synthesized | Vitamin K-Dependent | Function |
| --- | --- | --- | --- |
| **Factor II (Prothrombin)** | Liver | Yes | Serine protease in common pathway |
| **Factor VII** | Liver | Yes | Extrinsic pathway initiator |
| **Factor IX** | Liver | Yes | Intrinsic pathway cofactor |
| **Factor X** | Liver | Yes | Common pathway initiator |
| **Factor V** | Liver + Platelets | No | Cofactor (not enzyme) |
| **Factor VIII** | Endothelium | No | Intrinsic pathway cofactor |
| **Factor XI** | Liver | No | Contact factor |

**High-Yield:** Factor VII has the **shortest half-life (4–6 hours)** among vitamin K-dependent factors, making it the first to drop in vitamin K deficiency or warfarin therapy. This is why PT (which tests extrinsic pathway) is prolonged before aPTT in early vitamin K deficiency.

**Clinical Pearl:** Vitamin K deficiency or warfarin therapy prolongs PT selectively (tests extrinsic pathway with Factor VII), while aPTT remains normal initially. As deficiency worsens, aPTT also prolongs (Factors II, IX, X affected).

### Why Factor VII is the Answer

Factor VII is:
1. Synthesized exclusively in the **hepatocytes**
2. Requires vitamin K for γ-carboxylation of 10 glutamic acid residues in its N-terminal region
3. Essential for the extrinsic coagulation pathway (TF-Factor VII complex)
4. The most sensitive marker of hepatic synthetic function and vitamin K status

[cite:Robbins 10e Ch 4]

Answer

A. Factor VIII

Answer

B. Factor V

Answer

D. Factor XI

Which of the following coagulation factors is synthesized exclusively in the liver and requires vitamin K for its γ-carboxylation?

Explanation

Vitamin K-Dependent Coagulation Factors

The Vitamin K-Dependent Factors

Why Factor VII is the Answer

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Factor	Synthesized	Vitamin K-Dependent	Function
Factor II (Prothrombin)	Liver	Yes	Serine protease in common pathway
Factor VII	Liver	Yes	Extrinsic pathway initiator
Factor IX	Liver	Yes	Intrinsic pathway cofactor
Factor X	Liver	Yes	Common pathway initiator
Factor V	Liver + Platelets	No	Cofactor (not enzyme)
Factor VIII	Endothelium	No	Intrinsic pathway cofactor
Factor XI	Liver	No	Contact factor