Vitamin K: Recommended Supplementation Regimens
Newborn Prophylaxis
All newborns should receive a single intramuscular dose of 0.5 to 1.0 mg vitamin K1 within one hour of birth to prevent vitamin K deficiency bleeding. 1
Intramuscular Administration (Preferred Route)
- Dose: 1 mg vitamin K1 intramuscularly at birth 2
- Timing: Within the first hour after delivery 1
- This route is preferred for efficiency and reliability, providing superior protection against both classic and late vitamin K deficiency bleeding 2, 3
- Intramuscular prophylaxis is mandatory for preterm infants, those with cholestasis, impaired intestinal absorption, or whose mothers took medications interfering with vitamin K metabolism 2
Oral Administration (Alternative When IM Declined)
If parents decline intramuscular administration, oral regimens may be used but are less effective than IM prophylaxis for preventing late vitamin K deficiency bleeding 3:
Option 1 (Three-dose regimen):
- 2 mg vitamin K1 orally at birth
- 2 mg at 4–6 days
- 2 mg at 4–6 weeks 2
Option 2 (Weekly regimen):
- 2 mg vitamin K1 orally at birth
- 1 mg weekly for 3 months 2
Critical caveat: If the infant vomits or regurgitates within 1 hour of oral administration, repeat the dose 2. Parents must understand that oral regimens carry higher risk of late vitamin K deficiency bleeding if doses are missed 3.
Special Populations
- Preterm infants on parenteral nutrition: 10 μg/kg/day 4
- Children >12 months on parenteral nutrition: 200 μg/day 4
- Infants of mothers on anticoagulants or anticonvulsants: Must receive IM or slow IV vitamin K at birth, with repeated doses based on clinical status 4
Adult Deficiency Treatment
For adults with vitamin K deficiency, administer 100 mg per day orally, adjusting based on the underlying cause of deficiency. 4
Diagnostic Approach
- Plasma vitamin K1 concentrations <0.15 mg/L indicate depletion/deficiency 4
- PIVKA-II (undercarboxylated prothrombin) is the most sensitive and specific biomarker for subclinical vitamin K deficiency 4
- Measure vitamin K status in at-risk patients: those with steatorrhea (celiac disease, cystic fibrosis, short bowel syndrome), prolonged broad-spectrum antibiotic use, or chronic kidney disease 4
Maintenance Requirements
- Adequate intake: 1 μg/kg body weight per day (EFSA) or 120 μg for men and 90 μg for women (IOM) 4
- Enteral nutrition: At least 3.5–20 μg/100 kcal, typically meeting daily requirements 4
- Parenteral nutrition: 150 μg/day from multivitamin preparations, plus 6–300 μg/100 g from lipid emulsions depending on source 4
Common Causes of Deficiency
Vitamin K deficiency occurs most commonly with fat malabsorption syndromes (celiac disease, cystic fibrosis, short bowel), malnutrition, prolonged antibiotic therapy, and warfarin treatment 4.
Warfarin Reversal
For warfarin-associated major bleeding requiring emergent reversal, administer 4-factor prothrombin complex concentrate (4F-PCC) dosed by INR and body weight, plus 5–10 mg vitamin K1 intravenously by slow infusion over 15–30 minutes. 4
Dosing Algorithm for 4F-PCC + Vitamin K
| INR Range | 4F-PCC Dose | Vitamin K Dose |
|---|---|---|
| 2 to <4 | 25 U/kg IV | 5–10 mg IV slow infusion |
| 4 to 6 | 35 U/kg IV | 5–10 mg IV slow infusion |
| >6 | 50 U/kg IV | 5–10 mg IV slow infusion |
- Maximum 4F-PCC dose: 5,000 units (capped at 100 kg body weight) 4
- Vitamin K administration: Dilute in 25–50 mL normal saline and infuse over 15–30 minutes 4
- Onset of action: 4F-PCC corrects INR within 5–15 minutes; vitamin K begins effect at 4–6 hours, with maximum effect at 12–24 hours 4, 5
Rationale for Combined Therapy
Vitamin K alone takes 4–24 hours to normalize coagulation and is inadequate for emergency reversal 4. The 4F-PCC provides immediate correction, while vitamin K prevents rebound coagulopathy because 4F-PCC has a half-life of only 4–6 hours (factor VII) to 60 hours (factor II) 4.
Alternative When 4F-PCC Unavailable
If 4F-PCC is unavailable, administer fresh frozen plasma (FFP) 10–20 mL/kg IV plus vitamin K 10 mg IV, though this is less effective and carries volume overload risk 4.
Safety Considerations
- Do not exceed 10 mg vitamin K: Higher doses create a prothrombotic state and prevent re-anticoagulation for days 4, 5
- Anaphylactoid reactions: Occur in 3 per 100,000 IV doses; always give by slow infusion, never IV push 4, 5
- Avoid subcutaneous route: Absorption is unpredictable and not recommended 4
Non-Emergency Warfarin Reversal
For elevated INR without major bleeding:
- INR 4.5–10 without bleeding: Omit warfarin doses and give 2.5–5 mg vitamin K orally 4
- INR >10 without bleeding: Give 5–10 mg vitamin K orally 4
Important Caveats and Pitfalls
Vitamin K in Liver Disease
Vitamin K has minimal to no role in managing coagulopathy from hepatic synthetic dysfunction and should not be used routinely to correct INR in cirrhosis. 5
- Vitamin K is effective only when true deficiency exists (cholestasis, malabsorption, prolonged antibiotics, poor nutrition) 5
- In decompensated liver disease, a therapeutic trial of 10 mg vitamin K IV with INR reassessment at 12–24 hours can distinguish vitamin K deficiency (INR improves ≥0.5) from pure synthetic dysfunction (INR remains elevated) 5
- For cholestatic liver disease specifically, parenteral vitamin K supplementation is recommended 5
Patients on Anticoagulants
- Patients on vitamin K antagonists should avoid sudden major changes in vitamin K intake 4
- During continuous enteral nutrition, withhold feeding for 1 hour before and after anticoagulant administration to prevent interactions 4
- Higher vitamin K doses (>150 μg/day) during parenteral nutrition can cause vitamin K antagonist resistance 4
Toxicity
Vitamin K1 and K2 are not associated with toxicity 4. Synthetic vitamin K3 is toxic and no longer available 4.