Biochemistry — Vitamin K & Coagulation
Vitamin K gamma-carboxylates clotting factors. Warfarin blocks it. Heparin bypasses it entirely. This is how bleeding and clotting questions work on boards.
Vitamin K is needed for gamma (γ)-carboxylation — adding a third carboxyl group (COOH) to the vitamin K-dependent clotting factors.
Which factors? II, VII, IX, X (1972) plus Protein C & Protein S 🔑1972 — the year to remember. Factors 10, 9, 7, 2. Count down: X, IX, VII, II.
The math: Each factor has 10 glutamic acids on its carboxyl terminal. Each glutamic acid already has 2 carboxyl groups (α and β). So: 2 × 10 = 20 negative charges. Vitamin K adds the 3rd (gamma) group → now 30 negative charges.
These 30 negative charges attract calcium (Ca²⁺) released by platelets → this is how clotting factors are recruited to the site of injury. (why it matters)Without gamma-carboxylation, the factors float around uselessly. They exist but can't bind calcium, can't find platelets, can't form clots.
Protein C has the shortest half-life: 6 hours. Factor VII is next: 2 days.
Warfarin basics:
Protein C (anticoagulant, t½ = 6 hrs) has lost half its activity. But Factor VII (t½ = 2 days) is barely touched. You've knocked out the brakes before the engine.
The patient is now MORE likely to clot than before you started warfarin.
If the patient has a congenital Protein C deficiency, this happens even faster → warfarin-induced skin necrosis from microvascular thrombosis.
Heparin's t½ is also 6 hours. It activates antithrombin III, which directly blocks thrombin and factors IX, X, XI, XII (intrinsic pathway).
This provides anticoagulation protection while Protein C is depleted and before warfarin has had time to knock out enough clotting factors.
Factor VII is the first clotting factor to go (shortest t½ among the factors). It's in the extrinsic pathway, which is why we follow PT/INR.
Steady state for Factor VII: 5 × 2 days = 10 days. But by day 2, warfarin is starting to work. Patient stays on heparin for at least 2 days until warfarin has blocked Factor VII.
| Feature | Warfarin | Heparin (UFH) |
|---|---|---|
| Route | Oral | IV / SubQ |
| Mechanism | Blocks vitamin K recycling | Activates antithrombin III |
| Pathway | Extrinsic (+ common) | Intrinsic (IX, X, XI, XII) |
| Monitor | PT / INR | PTT |
| Reversal | Vitamin K IM (or FFP/PCC if bleeding) | Protamine sulfate |
| Pregnancy? | NO — teratogenic (crosses placenta) | Safe (charged, doesn't cross) |
| Onset | Days (need Factor VII depleted) | ~6 hours |
| Target INR | 2-3 | N/A (use PTT) |
| PTT target | N/A | 2.5-3.5 if cardiolipin/metallic valve |
Heparin Side Effects:
Low-Molecular Weight Heparin (LMWH):
Heparin Contraindications:
Gut flora makes:
When do you NOT have enough gut flora?