What are the indications, recommended dosing, and safety precautions for vitamin K supplementation in adults (including deficiency and warfarin reversal) and in newborns?

Vitamin K: Indications, Dosing, and Safety Precautions

Newborn Prophylaxis and Treatment

All newborns should receive a single intramuscular dose of 0.5 to 1.0 mg vitamin K1 (phytonadione) within one hour of birth to prevent hemorrhagic disease of the newborn. 1, 2

• Newborns have physiologically low vitamin K-dependent coagulation factors (II, VII, IX, X) and breast milk contains inadequate vitamin K, placing exclusively breastfed infants at particularly high risk for bleeding. 1, 3
• For treatment of active hemorrhagic disease in newborns, administer 1 mg vitamin K1 subcutaneously or intramuscularly; higher doses may be necessary if the mother received oral anticoagulants. 2
• A prompt response (shortened prothrombin time within 2-4 hours) confirms the diagnosis, while failure to respond indicates another coagulation disorder. 2
• Consider whole blood or component therapy if bleeding is excessive, but vitamin K1 must be given concurrently as transfusion alone does not correct the underlying disorder. 2

Warfarin Reversal in Adults

For patients with mechanical heart valves and uncontrollable bleeding requiring immediate anticoagulation reversal, administer 4-factor prothrombin complex concentrate (or its activated form) as the primary intervention. 4

• Four-factor prothrombin complex concentrate (factors II, VII, IX, X) has onset within 5-15 minutes and duration of 12-24 hours, making it more specific and reliable than fresh frozen plasma. 4
• For life-threatening bleeding, administer intravenous vitamin K1 10 mg in addition to prothrombin complex concentrate. 4
• Adjunctive intravenous vitamin K is reasonable after 4-factor prothrombin complex if resumption of warfarin therapy is not anticipated for 7 days. 4
• The onset of vitamin K effect depends on route: intravenous administration achieves maximum effect within 6-12 hours, while oral supplementation requires approximately 24 hours. 5

Supratherapeutic INR Without Active Bleeding

• For patients with mechanical prosthetic valves and INR >5.0 who are not actively bleeding, the benefit of oral vitamin K (in addition to temporary warfarin withdrawal) is uncertain and should be individualized based on INR magnitude, bleeding risk, and desired INR range. 4
• Rapid INR reduction to subtherapeutic levels may paradoxically increase thromboembolism risk in patients with mechanical valves. 4

Vitamin K Deficiency in Adults

Administer 2.5 to 25 mg vitamin K1 for most cases of adult vitamin K deficiency, with doses up to 50 mg reserved for severe deficiency. 2

High-Risk Populations Requiring Supplementation

• Cystic fibrosis patients: Vitamin K status is often suboptimal and deficient in all patients with CF-related liver disease due to fat malabsorption, long-term antibiotic use, and hepatic dysfunction. 4

  • Infants with CF: 0.3-1.0 mg/day vitamin K1 4
  • Older children and adults with CF: 1-10 mg/day vitamin K1 depending on age and risk factors 4
  • Daily administration is preferred due to low vitamin K storage capacity 4
  • Special attention needed for CF newborns, exclusively breastfed CF infants, those on broad-spectrum antibiotics, and those with liver disease or severe malabsorption 4

• Fat malabsorption syndromes: Patients with short bowel syndrome, inflammatory bowel disease, or chronic cholestatic liver disease require supplementation (200 mg/day improves neurological symptoms after several months). 4

• Long-term antibiotic therapy: Antibiotics decrease vitamin K synthesis by intestinal bacteria. 4, 3

Clinical Manifestations of Deficiency

• Vitamin K deficiency primarily affects blood clotting, with hemorrhage as the main clinical consequence. 3, 6
• In adults with chronic fat malabsorption, early deficiency is generally asymptomatic; prolonged deficiency causes neurological symptoms including balance/coordination disorders, peripheral neuropathy, and muscle weakness. 4
• Deficiency may contribute to low bone mineral density and increased fracture risk. 4, 7

Parenteral and Enteral Nutrition

Adults receiving parenteral nutrition should receive at least 200 μg/day vitamin K1, while those on enteral nutrition require at least 15 mg α-tocopherol per day with 1500 kcal (note: this appears to reference vitamin E; vitamin K in EN formulas typically provides 3.5-20 μg/100 kcal). 5

• Lipid emulsions in parenteral nutrition contain 6-300 μg phylloquinone per 100 g lipid; weekly IV supply of 250-500 μg from lipids alone is sufficient to restore and maintain normal plasma vitamin K. 4, 5
• Adult multivitamin preparations add approximately 150 μg vitamin K, which covers requirements and maintains carboxylation status of non-coagulation proteins. 4, 5
• Standard enteral nutrition formulas deliver 3.5-20 μg vitamin K per 100 kcal, generally meeting recommended daily intake. 4, 5

Critical Safety Precautions

Anticoagulant Interactions

Patients receiving vitamin K antagonists (warfarin) should NOT receive vitamin K supplements during stable anticoagulation, as even modest supplementation can cause anticoagulant resistance. 4

• Vitamin K doses exceeding 150 μg can overcome warfarin's anticoagulant effect and produce resistance. 4, 5
• In patients on enteral nutrition receiving warfarin, interrupt EN administration 1 hour before and after anticoagulant dosing to minimize interaction. 4
• Paradoxically, maintaining a constant daily vitamin K intake at recommended levels (65-80 μg/day) may actually improve warfarin stability compared to erratic intake. 8
• Monitor coagulation parameters closely when administering vitamin K to patients on anticoagulants. 5

Administration Route Safety

When intravenous or intramuscular administration is necessary, inject vitamin K very slowly, not exceeding 1 mg per minute, as rapid IV administration can cause rare but severe anaphylactoid reactions. 2

• Subcutaneous route is preferred when possible; IV/IM routes should only be used when unavoidable. 2
• Rare anaphylactoid reactions including bronchospasm and cardiac arrest have occurred with IV vitamin K1 administration. 5
• Protect vitamin K preparations from light at all times. 2

Toxicity Profile

• Natural vitamin K forms (K1 phylloquinone and K2 menaquinones) have no known toxicity even at high supplemental doses; no upper safety limit has been established. 4, 5
• Synthetic vitamin K3 (menadione) is highly toxic and contraindicated, causing jaundice, hemolytic anemia, and kernicterus in infants. 5
• Vitamin E supplements may induce bleeding risk by decreasing γ-carboxylation of prothrombin; individuals on anticoagulants or with vitamin K deficiency should not take vitamin E supplements without medical supervision. 4

Monitoring Vitamin K Status

• Plasma/serum phylloquinone concentration is the primary marker of recent vitamin K intake; levels <0.15 mg/L indicate deficiency. 5
• PIVKA-II (protein induced by vitamin K absence) measures undercarboxylated prothrombin and is a sensitive functional marker of hepatic subclinical deficiency, though not routinely used due to cost. 4, 5
• Prothrombin time is insensitive, only becoming elevated in severe deficiency. 4
• For cystic fibrosis patients, measure vitamin K status when clinically indicated (signs of deficiency, liver disease, prolonged antibiotic use). 4

Dietary Considerations

• Green leafy vegetables (kale, spinach, collards), cruciferous vegetables, asparagus, prunes, peas, and parsley are rich dietary sources of vitamin K1. 5, 9
• Plant oils (soybean, canola) and prepared foods containing these oils (baked goods, margarines, salad dressings) contribute significant dietary vitamin K. 8
• Intestinal bacteria synthesize vitamin K2 (but not K1) and contribute approximately half of vitamin K requirements under normal conditions. 4, 6