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 **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]