A 62-year-old man with chronic liver cirrhosis (Child-Pugh Class C) presents to the emergency department with spontaneous bleeding from esophageal varices. On examination, he has jaundice, ascites, and spider angiomata. Laboratory investigations show PT/INR 4.2 (normal <1.2), platelet count 80,000/μL, and albumin 2.1 g/dL. Fresh frozen plasma and platelet transfusions are initiated. Which fat-soluble vitamin deficiency is most likely contributing to his coagulopathy and should be administered urgently?

Explanation

## Clinical Context This patient has advanced cirrhosis with severe coagulopathy (markedly elevated INR) and bleeding. The combination of liver disease, malabsorption, and impaired synthesis of clotting factors creates a critical need for vitamin K. ## Why Vitamin K? **Key Point:** Vitamin K is a cofactor for γ-carboxylation of prothrombin (Factor II), Factor VII, Factor IX, and Factor X — all vitamin K-dependent clotting factors synthesized in the liver. **High-Yield:** In cirrhosis, two mechanisms cause vitamin K deficiency: 1. **Malabsorption** — impaired bile salt secretion reduces fat-soluble vitamin absorption in the small intestine. 2. **Impaired hepatic synthesis** — the liver cannot efficiently convert vitamin K to its active form (vitamin K hydroquinone) or synthesize the clotting factors themselves. **Clinical Pearl:** The PT/INR is exquisitely sensitive to vitamin K-dependent factor deficiency. An INR >4 in cirrhosis with bleeding is a classic indication for IV vitamin K (10 mg slow IV, repeated daily for 3 days) *before* or *alongside* fresh frozen plasma. ## Mechanism of Action Vitamin K (phylloquinone, K1) is reduced to its active hydroquinone form by hepatic reductase. This reduced form serves as a cofactor for vitamin K-dependent carboxylase, which catalyzes γ-carboxylation of glutamic acid residues on the N-terminal region of clotting factors. These γ-carboxyl groups bind calcium and phospholipids, enabling the factors to participate in the coagulation cascade. ## Differential: Why Not the Others? | Vitamin | Role in Coagulation | Deficiency in Cirrhosis | Urgency in Bleeding | |---------|---------------------|------------------------|---------------------| | **A** | Epithelial integrity, immune function | Present but not directly hemostatic | Low | | **D** | Calcium absorption, bone health | Present but not directly hemostatic | Low | | **E** | Antioxidant; mild platelet dysfunction if severe | Rarely causes acute bleeding | Low | | **K** | γ-carboxylation of Factors II, VII, IX, X | **Primary cause of PT prolongation** | **URGENT** | **Mnemonic for vitamin K-dependent factors:** **PIVKA** = **P**rothrombin, **I**ntermediate (Factor VII), **V**itamin K-dependent, **K**inase (Factor X), **A**ntihemophilic (Factor IX). Or simply: **2, 7, 9, 10** (the four factors). ## Clinical Management 1. **IV vitamin K 10 mg** (slow infusion, not bolus — risk of anaphylaxis) daily × 3 days. 2. **Fresh frozen plasma** for immediate factor replacement (contains all vitamin K-dependent factors). 3. **Prothrombin complex concentrate (PCC)** if available — more efficient than FFP, lower volume load. 4. **Endoscopic variceal ligation** for definitive hemostasis. **Warning:** Oral vitamin K is ineffective in acute cirrhosis because absorption is impaired. IV route is mandatory. [cite:Harrison 21e Ch 297]