Vitamin K Supplementation: When and How to Administer
Universal Newborn Prophylaxis
All newborns should receive vitamin K prophylaxis at birth to prevent life-threatening vitamin K deficiency bleeding (VKDB), with intramuscular administration being the most effective and reliable route. 1, 2, 3
Recommended Dosing for Healthy Term Newborns
The American Academy of Pediatrics recommends 0.5-1.0 mg vitamin K1 (phylloquinone) intramuscularly within one hour of birth as the gold standard. 1, 3 This single IM dose reduces the risk of VKDB from 1 in 59 (without prophylaxis) to 1 in 100,000. 4
Alternative oral regimens (less effective than IM but acceptable if IM is refused):
- 3 doses of 2 mg orally: at birth, at 4-6 days, and at 4-6 weeks 1, 5
- 2 mg at birth followed by weekly 1 mg doses for 3 months 1, 2
Critical caveat: Oral prophylaxis is not appropriate for preterm infants, those with cholestasis, impaired intestinal absorption, infants too unwell to take oral medication, or those whose mothers took medications interfering with vitamin K metabolism. 5 If the infant vomits within 1 hour of oral administration, repeat the dose. 5
Preterm Infants on Parenteral Nutrition
Preterm infants require 10 μg/kg/day of vitamin K1 when receiving parenteral nutrition. 1, 2
High-Risk Populations Requiring Ongoing Supplementation
Exclusively Breastfed Infants
All exclusively breastfed infants require vitamin K supplementation because breast milk contains very low levels of vitamin K. 6, 2 After initial newborn prophylaxis, continue supplementation throughout the breastfeeding period. 2
Infants with Maternal Drug Exposure
Infants whose mothers took anticonvulsants, anticoagulants (warfarin), or antituberculosis drugs require:
- Higher initial doses (may need more than the standard 1 mg) 3
- Antenatal maternal prophylaxis: 10-20 mg/day orally for 15-30 days before delivery prevents early VKDB 7
- Repeated neonatal doses based on clotting factor profiles 7
Cystic Fibrosis Patients
Vitamin K status is often suboptimal in all CF patients and deficient in all those with CF-related liver disease. 6 Deficiency can cause intracranial hemorrhage in infants and contributes to low bone mineral density. 6
Recommended dosing for CF patients:
- Infants: 0.3-1.0 mg/day 6, 2
- Older children and adults: 1-10 mg/day depending on age 6, 2
- Higher doses for those with documented low levels, long-term antibiotic use, liver disease, or severe malabsorption 6
Daily administration is preferred due to vitamin K's low storage capacity. 6, 2
Adults on Parenteral Nutrition
Adults receiving parenteral nutrition require 200 μg/day of vitamin K1 (150 μg supplemental plus variable amounts in lipid emulsion). 2, 8 This dose maintains hemostasis but may be excessive for patients on warfarin, potentially jeopardizing anticoagulant control. 8
Other Malabsorption Conditions
Patients with celiac disease, short bowel syndrome, cholestasis, or alpha-1-antitrypsin deficiency require supplementation due to fat malabsorption. 6, 2
Treatment of Active Vitamin K Deficiency
Hemorrhagic Disease of the Newborn
For treatment (not prophylaxis): 1 mg vitamin K1 subcutaneously or intramuscularly. 3 A prompt response (shortening of prothrombin time within 2-4 hours) is diagnostic of VKDB; failure to respond indicates another coagulation disorder. 1, 3 Higher doses may be necessary with maternal anticoagulant use, and whole blood or component therapy may be needed for excessive bleeding. 3
Anticoagulant-Induced Prothrombin Deficiency in Adults
Initial dose: 2.5-10 mg or up to 25 mg (rarely 50 mg may be required). 3 If prothrombin time hasn't shortened satisfactorily within 6-8 hours, repeat the dose. 3 Maximum effect occurs within 6-12 hours for IV administration versus 24 hours for oral. 2
Other Causes of Hypoprothrombinemia
Dosing: 2.5-25 mg or more (rarely up to 50 mg), with amount and route depending on severity. 3 Consider discontinuing or reducing interfering drugs (salicylates, antibiotics) as an alternative to vitamin K administration. 3
Administration Routes and Safety
Vitamin K1 (phylloquinone) is the safest form and is preferred over menadione salts. 6, 2 Vitamin K3 (menadione) is toxic and should never be used. 6
Route considerations:
- Subcutaneous is preferred when possible 3
- Intramuscular is most reliable for newborns 1, 2
- Intravenous should be given very slowly (not exceeding 1 mg per minute) due to rare anaphylactoid reactions with bronchospasm and cardiac arrest 2, 3
- Oral takes longer to work and depends on compliance 2
Vitamin K1 toxicity is not a concern—there are no known adverse effects of phylloquinone supplementation. 6, 2 The formulations approved in the United States have not been associated with childhood leukemia or other health problems. 4
Monitoring Vitamin K Status
There is no single established biomarker for vitamin K status. 6 Available options include:
- Plasma phylloquinone concentration <0.15 μg/L indicates depletion/deficiency 6
- PIVKA-II (undercarboxylated prothrombin) is the most sensitive marker of subclinical hepatic deficiency and should be used for at-risk patients when locally available 6, 1, 2
- Prothrombin time (PT) is insensitive, only becoming elevated in severe deficiency 6
- Undercarboxylated osteocalcin reflects bone vitamin K status but lacks established cut-offs 6
For CF patients, monitor vitamin K status at least annually and 3-6 months after dosage changes. 6
Special Clinical Situations
Patients on Warfarin
Anticoagulant control may improve with regular vitamin K intake at recommended doses (150 μg), but higher doses can cause warfarin resistance. 6 Monitor coagulation parameters closely when administering vitamin K to anticoagulated patients. 2
Women Planning Pregnancy
All women planning pregnancy should receive 400 μg folic acid daily (not vitamin K) in the preconceptional period and first trimester. 6 Vitamin K supplementation during pregnancy is only indicated if the mother is on anticonvulsants or prolonged antibiotic therapy. 9