Reversal agent · Vitamin
Vitamin K
Also called phytonadione
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Heparin vs Warfarin: aPTT vs INR, HIT, Bridging, Antidotes and DOAC Reversal
Indications
- Warfarin reversal for major bleeding or urgent surgery, IV with 4F-PCC (PCC acts in minutes; vitamin K sustains it)
- INR over 10 without bleeding, by mouth (CHEST 2012)
- Deficiency from poor intake with antibiotics, malabsorption or cholestasis
- Superwarfarin rodenticide poisoning, often for months
- Vitamin K deficiency bleeding in newborns, prevention and treatment (label)
- Warfarin-treated patients when HIT is diagnosed (ASH 2018)
Dosing
| Where | Dose |
|---|---|
| Metabolic and electrolyte boluses | Vitamin K: 5–10 mg IV slowly (no faster than 1 mg/min) |
Mechanism of action
Phytonadione (vitamin K1) is the cofactor for γ-glutamyl carboxylase in the liver's endoplasmic reticulum. In its reduced (hydroquinone) form it lets the enzyme carboxylate glutamate residues in the Gla domains of factors II, VII, IX and X and proteins C, S and Z, and it is oxidized to vitamin K epoxide. The γ-carboxyglutamate residues bind calcium, so the factors can attach to phosphatidylserine on activated platelets. Warfarin blocks VKORC1, which recycles the epoxide; large doses bypass the block because a warfarin-insensitive reductase (FSP1) reduces vitamin K directly.
Pharmacology
- Hematologic: the INR responds first because factor VII has the shortest half-life (about 5–6 h); full correction needs new factors and fails if the liver cannot make them
- Hematologic: no effect on heparin (label), LMWH, DOACs or antiplatelet drugs
- Hematologic: large doses cause temporary resistance to warfarin (label)
- Cardiovascular: rare anaphylactoid reactions during IV injection: flushing, hypotension, bradycardia or tachycardia, bronchospasm and arrest
Pharmacokinetics
| Onset | IV 1–2 h; oral 6–10 h (labels); SC slow and erratic |
|---|---|
| Peak | IV: bleeding controlled in 3–6 h, INR often normal by 12–14 h (label); oral matches IV by 24 h (Lubetsky 2003) |
| Half-life | IV: 22 min, then about 2 h (DrugBank) |
| Distribution | Fat-soluble, carried in lipoproteins; Vd about 20 L (DrugBank); small stores; little crosses the placenta |
| Metabolism | Liver: epoxide cycle; side chain shortened, then glucuronidated |
| Elimination | Bile and urine as metabolites; almost none unchanged (label) |
| Bioavailability | Oral absorption needs bile salts and runs through intestinal lymph |
Chemistry
- 2-methyl-3-phytyl-1,4-naphthoquinone (phylloquinone), C₃₁H₄₆O₂, MW 450.7: a naphthoquinone ring with a 20-carbon phytyl tail
- Only the trans (E) isomer is active; USP allows up to 21% of the inactive cis (Z) isomer
- A non-ionizable, water-insoluble oil, so the injection is an aqueous dispersion with a polyoxyethylated fatty acid surfactant, dextrose and benzyl alcohol 9 mg/mL (Hospira); 2 or 10 mg/mL, pH about 6.3
- Light-sensitive: protect from light at all times; dilute only in NS, D5W or D5NS (label)
Adverse effects and cautions
In the one-pagers
- Bleeding, Reversal, HIT and DICReversing anticoagulants in major bleeding: Warfarin: 4F-PCC plus vitamin K 10 mg IV (slow): PCC 25–50 units/kg by INR; FFP only if no PCC
- Blood Products and TransfusionAnticoagulant reversal: Warfarin: 4F-PCC 25 to 50 units/kg by INR, plus vitamin K 5 to 10 mg slow IV: PCC corrects INR in about 30 min; vitamin K takes hours
- Subarachnoid HemorrhageUntil the aneurysm is secured: Reverse anticoagulants now: warfarin, 4F-PCC plus IV vitamin K; dabigatran, idarucizumab; factor Xa inhibitors, 4F-PCC; heparin, protamine.
- LVAD BasicsComplications: bleeding, stroke, infection, RV failure: Hemorrhagic stroke: No supratherapeutic INR, control MAP: Reverse warfarin (4F-PCC, vitamin K); neurosurgery
- Neuro: ICP and StrokeHemorrhagic stroke (ICH): Warfarin, INR 2 or more: 4F-PCC (not FFP) plus IV vitamin K
- Trauma: Primary and Secondary SurveyOlder adults and pregnancy: After 65, vital signs mislead: beta-blockers and pacemakers fix the heart rate, and chronic hypertension makes a normal-looking pressure relative hypotension. SBP below 90 identifies only 4–5% of seriously injured older adults, so the 2021 national field triage guideline uses SBP below 110 or heart rate above SBP. An EAST multicenter study (Ho 2025) supports head and ce
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Sources
- FDA label: Vitamin K1 injection (2025)
- FDA label: phytonadione tablets (2024)
- Britt 2018 (vitamin K reactions)
- Mishima 2022 (FSP1)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.