Vitamin K is required for gamma-carboxylation of glutamate residues in coagulation factors II, VII, IX, and X. Warfarin inhibits vitamin K epoxide reductase (VKOR). Which additional vitamin K-dependent proteins are clinically relevant and have anticoagulant/anti-calcification roles?

• A Antithrombin III and alpha-2 macroglobulin — both inhibited by warfarin
• B Fibrinogen and Factor XIII — both cross-linking and clot-stabilising proteins
• C Plasminogen and tissue plasminogen activator — fibrinolytic proteins
• D Protein C, Protein S, and Protein Z — anticoagulant proteins; Matrix Gla protein (MGP) — inhibits vascular calcification ✓

Explanation

In addition to procoagulant factors II, VII, IX, X, vitamin K-dependent gamma-carboxylation is required for anticoagulant proteins C and S (and Protein Z). In warfarin therapy, these anticoagulant proteins are also depleted — early warfarin initiation can paradoxically cause a prothrombotic state (warfarin-induced skin necrosis) due to shorter half-lives of Protein C and S compared to procoagulant factors. Matrix Gla protein (MGP) in vascular smooth muscle cells requires vitamin K-dependent carboxylation to inhibit calcification — warfarin inhibiting MGP activation may contribute to accelerated vascular calcification in patients on long-term warfarin. Osteocalcin is another bone Gla protein.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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