Vitamin K deficiency impairs the synthesis of which coagulation factors?

Explanation

## Vitamin K-Dependent Coagulation Factors **Key Point:** Vitamin K is a cofactor for γ-carboxylation of glutamic acid residues in coagulation factors. Deficiency impairs synthesis of **Factors II, VII, IX, and X** — collectively called the **prothrombin complex factors** (or PIVKA factors when undercarboxylated). **Mnemonic:** **PIVKA** or **II, VII, IX, X** — Remember: "**2, 7, 9, 10**" or "**Vitamin K-dependent = Prothrombin Complex**" ### Mechanism of Vitamin K Action 1. Vitamin K (as phylloquinone, K1, or menaquinone, K2) is reduced to its active hydroquinone form 2. Hydroquinone acts as a cofactor for γ-glutamyl carboxylase 3. This enzyme γ-carboxylates glutamic acid residues (Glu → Gla) in the N-terminal region of vitamin K-dependent factors 4. Gla residues enable Ca^2+^ binding, which anchors factors to phospholipid membranes — essential for the coagulation cascade ### Vitamin K-Dependent Factors | Factor | Synonym | Role | | --- | --- | --- | | **II** | Prothrombin | Serine protease; central to both extrinsic and intrinsic pathways | | **VII** | Proconvertin | Extrinsic pathway; shortest half-life (~6 hours) | | **IX** | Christmas factor | Intrinsic pathway | | **X** | Stuart–Prower factor | Common pathway | | **Protein C** | — | Natural anticoagulant; also vitamin K-dependent | | **Protein S** | — | Cofactor for Protein C; also vitamin K-dependent | **High-Yield:** Factors V, VIII, XIII, and fibrinogen (I) are **NOT** vitamin K-dependent; they are synthesized normally in vitamin K deficiency. ### Clinical Consequences of Vitamin K Deficiency - **Prolonged PT** (Factor VII has shortest half-life; PT rises first) - **Prolonged aPTT** (Factors II, IX, X involved in intrinsic pathway) - **Normal bleeding time** (platelet function intact) - **Hemorrhage risk:** GI bleeding, hematuria, intracranial hemorrhage ### Causes of Vitamin K Deficiency in India - Malabsorption (celiac disease, cystic fibrosis, biliary obstruction) - Antibiotic use (disrupts gut flora producing K2) - Dietary insufficiency (rare in developed countries; more common in malnourished populations) - Warfarin therapy (intentional antagonism) **Clinical Pearl:** In a bleeding patient with prolonged PT but normal platelet count and bleeding time, suspect vitamin K deficiency or liver disease. Correct PT with fresh frozen plasma or vitamin K (IV/IM); PT correction within 12–24 hours confirms vitamin K deficiency (vs. liver disease, where PT does not correct). [cite:Harrison 21e Ch 139; Robbins 10e Ch 12]