What is the recommended dose and route of administration for vitamin K (Vitamin K1, phytonadione)?

Vitamin K Dose and Administration

For life-threatening bleeding or emergency surgery requiring immediate warfarin reversal, administer 10 mg intravenous vitamin K by slow infusion over 15-30 minutes plus 4-factor prothrombin complex concentrate (PCC) dosed by INR and body weight. 1, 2

Life-Threatening Bleeding or Emergency Surgery

The gold standard is 10 mg IV vitamin K plus 4-factor PCC immediately:

• Vitamin K dose: 10 mg intravenous, administered slowly over 15-30 minutes in 25-50 mL normal saline 1
• PCC dosing algorithm based on INR: 1, 3
  • INR 2 to <4: 25 U/kg IV
  • INR 4-6: 35 U/kg IV
  • INR >6: 50 U/kg IV
  • Maximum dose: 5,000 units (capped at 100 kg body weight)
• Onset of action: PCC achieves INR correction within 5-15 minutes, while vitamin K alone takes 4-6 hours IV or 18-24 hours orally 1, 3
• Critical rationale: Vitamin K must be co-administered with PCC because factor VII in PCC has only a 6-hour half-life; vitamin K stimulates endogenous production of vitamin K-dependent factors for sustained reversal 1, 3, 4

Major Bleeding (Non-Life-Threatening)

For significant bleeding with hemodynamic stability:

• Vitamin K dose: 5-10 mg intravenous by slow infusion over 30 minutes 1, 3
• Consider adding PCC if bleeding is at critical sites (intracranial, intraspinal, intraocular, pericardial, retroperitoneal, intra-articular, or intramuscular with compartment syndrome) 3
• Recheck INR 30-60 minutes after administration to confirm adequate reversal 1, 2

Elevated INR Without Bleeding

Management is stratified by INR level and bleeding risk factors:

INR 5.0-9.0 Without Bleeding

• Low bleeding risk: Simply withhold warfarin and monitor serial INR; no vitamin K needed 1, 3, 4
• High bleeding risk (advanced age >65-75 years, history of bleeding, concomitant antiplatelet drugs, renal failure, alcohol use): Add oral vitamin K 1-2.5 mg, which achieves INR <4.0 within 24 hours in 85% of patients 3, 4

INR >10 Without Bleeding

• Vitamin K dose: 3-5 mg oral vitamin K immediately, plus withhold warfarin 3, 4
• Recheck INR within 24 hours 3

Supratherapeutic INR in Mechanical Valve Patients

• Use low-dose vitamin K (1-2 mg oral) to avoid difficulty achieving therapeutic INR post-procedure 1, 3
• Higher doses discouraged because 10 mg vitamin K creates warfarin resistance for up to one week, requiring heparin bridging if warfarin needs resumption 3, 4

Route of Administration Comparison

Intravenous route is superior for urgent reversal:

• IV administration: Achieves partial correction in 4-6 hours; 44% of patients reach INR ≤2 within 12 hours 1, 5, 6
• Oral administration: Takes 18-24 hours for effect; only 14% reach INR ≤2 within 12 hours 1, 6
• Subcutaneous route: Unpredictable absorption and not recommended 1, 7
• Anaphylactic reactions: Occur in 3 per 100,000 IV doses via non-IgE mechanism (possibly due to polyoxyethylated castor oil solubilizer), manifesting as cardiac arrest, severe hypotension, bradycardia/tachycardia, dyspnea, and bronchospasm 3, 4

Critical Monitoring Parameters

Serial INR monitoring is essential:

• Immediate recheck: 15-60 minutes after PCC administration 2, 3
• Early monitoring: Every 6-8 hours for first 24-48 hours 2, 3
• Extended monitoring: Continue regularly over next week, as some patients require >1 week to clear warfarin and may need additional vitamin K 3
• Watch for INR rebound: If INR remains ≥1.4 within first 24-48 hours after initial PCC, consider additional vitamin K 10 mg IV 2

Special Populations

Newborns and Infants

• Prophylaxis: 0.5-1 mg intramuscular within one hour of birth 8, 9
• Treatment of hemorrhagic disease: 1 mg subcutaneous or intramuscular; higher doses may be necessary if mother received oral anticoagulants 8
• Oral regimen alternative: 3 doses of 2 mg oral at birth, 4-6 days, and 4-6 weeks; or 2 mg oral at birth plus weekly 1 mg for 3 months 9
• Intramuscular route preferred for efficiency and reliability; oral route inappropriate for preterm infants, cholestasis, impaired intestinal absorption, or maternal medications interfering with vitamin K metabolism 9

Mechanical Valve Patients

• Avoid high-dose vitamin K (>2 mg) to prevent prolonged warfarin resistance 1, 3
• For uncontrollable bleeding: 4-factor PCC is reasonable; adjunctive IV vitamin K reasonable if resumption of warfarin not anticipated for 7 days 1

Common Pitfalls to Avoid

Critical errors that compromise patient outcomes:

• Never rely solely on vitamin K without PCC in life-threatening bleeding—vitamin K alone does not provide immediate correction 2, 3
• Never exceed 10 mg vitamin K as higher doses create prothrombotic state and prevent re-warfarinization for days 3, 4
• Never use subcutaneous route due to unpredictable absorption 1, 7
• Never delay reversal while waiting for fresh frozen plasma preparation when PCC is available—time to correction is critical for preventing hematoma expansion 2
• Never use 3-factor PCC when 4-factor PCC is available, as 4-factor provides more complete factor replacement and lower thrombotic risk 2, 3
• Never fail to administer vitamin K concurrently with PCC/FFP in major bleeding, which leads to INR rebound 2
• Never overlook thromboembolism risk: PCC use increases venous and arterial thrombosis risk (7.2-12% within 30 days); consider thromboprophylaxis as early as possible after bleeding control 2, 3

Resuming Anticoagulation

Timing depends on bleeding control and risk assessment:

• Do not restart warfarin until: Bleeding completely controlled, source identified and treated, patient hemodynamically stable, and indication for anticoagulation still exists 3
• Delay restart if: Bleeding at critical site, high rebleeding risk, surgical procedures planned, or source remains unidentified 3
• Dose reduction: Reduce weekly warfarin dose by 20-30% to prevent recurrence of supratherapeutic INR 3