Which of the following clotting factors is needed for gamma-glutamyl carboxylase?

Correct Answer: A. Factors II, VII, IX, and X

Gamma-glutamyl carboxylase (GGCX) is a vitamin K-dependent enzyme that catalyzes the post-translational carboxylation of glutamic acid residues to gamma-carboxyglutamic acid (Gla residues) in clotting factors. This modification is essential for calcium binding and phospholipid interaction, enabling proper hemostatic function. The four vitamin K-dependent clotting factors are Factors II (prothrombin), VII, IX, and X—collectively remembered as the "PIVKA factors" (Proteins Induced by Vitamin K Absence). These factors require gamma-carboxylation for their biological activity. Vitamin K acts as a cofactor for GGCX; warfarin and other coumarins inhibit vitamin K recycling, preventing carboxylation and causing a prolonged PT/INR in Indian patients on anticoagulation. Factors V, VIII, XI, and XII are vitamin K-independent serine proteases that do not undergo gamma-carboxylation. This distinction is clinically critical: vitamin K deficiency or warfarin therapy selectively impairs Factors II, VII, IX, and X, explaining why PT is prolonged before aPTT in early warfarin therapy (Factor VII has the shortest half-life). Indian guidelines for anticoagulation management and reversal of warfarin toxicity (using fresh frozen plasma or vitamin K) rely on understanding this specific subset of vitamin K-dependent factors.

Why the other options are wrong

B. Factors II, VIII, IX, X — This option incorrectly includes Factor VIII, which is a vitamin K-independent factor. Factor VIII is synthesized in the liver but does NOT undergo gamma-carboxylation and is not affected by vitamin K deficiency or warfarin. The NBE trap here is pairing Factor VIII with the correct vitamin K-dependent factors to test whether students confuse the entire coagulation cascade. Factor VIII deficiency causes hemophilia A, which is unrelated to vitamin K status. C. Factors II, VIII, X, XI — This option contains two errors: Factor VIII is vitamin K-independent (as above), and Factor XI is also NOT vitamin K-dependent. Factor XI is a contact factor involved in the intrinsic pathway but does not require gamma-carboxylation. This option may trap students who memorize coagulation factors by pathway (intrinsic vs. extrinsic) without understanding the biochemical basis of vitamin K dependence. Factor XI deficiency causes mild bleeding. D. Factors II, VII, IX, XI — This option correctly lists three vitamin K-dependent factors (II, VII, IX) but incorrectly includes Factor XI, which is vitamin K-independent. The NBE trap is substituting Factor X (the correct fourth vitamin K-dependent factor) with Factor XI, which is a contact factor in the intrinsic pathway. Students who confuse 'intrinsic pathway factors' with 'vitamin K-dependent factors' fall into this trap, as both involve Factors IX and XI.

High-Yield Facts

Mnemonics

PIVKA Factors Prothrombin (II), Intermediate (VII), Vitamin K-dependent, Koagulation factors, Activated = Factors II, VII, IX, X. Use when identifying vitamin K-dependent factors in any clinical scenario (warfarin, vitamin K deficiency, neonatal hemorrhage). 2-7-9-10 Rule Vitamin K-dependent clotting factors are 2, 7, 9, 10 (II, VII, IX, X). Memorize the numeric sequence; all others are vitamin K-independent. Fastest recall method for board exams.

NBE Trap

NBE pairs Factor VIII or XI with the correct vitamin K-dependent factors to test whether students understand the biochemical basis (gamma-carboxylation) versus pathway classification (intrinsic vs. extrinsic). Students who confuse "coagulation cascade pathways" with "vitamin K dependence" will select options B, C, or D.

Clinical Pearl

In an Indian neonate with hemorrhagic disease of the newborn (vitamin K deficiency), vitamin K1 supplementation corrects only the PT (Factors II, VII, IX, X) while leaving aPTT normal—a key clinical sign that distinguishes vitamin K deficiency from other coagulopathies. Similarly, in a patient on warfarin presenting with bleeding, fresh frozen plasma replaces all vitamin K-dependent factors, but the effect is temporary; vitamin K1 (phytonadione) is the definitive reversal agent.

_Reference: KD Tripathi Pharmacology Ch. 13 (Anticoagulants); Robbins Pathology Ch. 4 (Hemostasis); Harrison Principles of Internal Medicine Ch. 139 (Coagulation Disorders)_