What is the recommended therapeutic and maintenance dosing of vitamin K1 for children with progressive familial intrahepatic cholestasis (PFIC)?

Vitamin K Dosing in PFIC (Progressive Familial Intrahepatic Cholestasis) in Children

For children with PFIC, administer vitamin K1 (phylloquinone) at 5-10 mg daily orally as maintenance therapy, with higher doses (up to 10 mg daily) reserved for those with documented deficiency, severe cholestasis, or active bleeding risk. 1

Understanding Vitamin K Deficiency in PFIC

Children with PFIC are at extremely high risk for vitamin K deficiency due to impaired bile secretion, which is essential for fat-soluble vitamin absorption. 2 This deficiency can manifest as severe coagulopathy with life-threatening bleeding, including intracranial hemorrhage, subcutaneous hematomas, and bruising that may mimic non-accidental injury. 3, 4

• PFIC patients have cholestasis with fat malabsorption, making them unable to absorb dietary vitamin K regardless of intake. 5, 2
• Bleeding complications are well-documented in PFIC, with cases reporting INR values as high as 12 and multiple intracranial bleeds in untreated patients. 6, 3

Maintenance Dosing Strategy

Start with 5 mg daily of vitamin K1 for all children with PFIC beyond infancy, and titrate up to 10 mg daily based on clinical response and coagulation parameters. 1

• For infants under 12 months with PFIC, use 0.3-1.0 mg daily, though this age group typically requires the higher end of this range (1 mg daily) given the severity of cholestasis. 5
• For children 1 year and older, the standard maintenance dose is 5 mg daily, which can be increased to 10 mg daily for those with persistent coagulopathy or documented low vitamin K levels. 5, 1
• Daily administration is mandatory—never use weekly or intermittent dosing in PFIC patients, as vitamin K has low storage capacity and cholestasis prevents adequate absorption even with daily dosing. 5, 1

Acute/Emergency Treatment

For active bleeding or severe coagulopathy (INR >3-4), administer 5-10 mg vitamin K1 intravenously by slow injection, with repeat dosing every 12-24 hours until coagulation normalizes. 6

• Intravenous vitamin K1 can normalize coagulation abnormalities within 1 hour in cholestatic patients with severe bleeding. 6
• Always use slow IV injection (not to exceed 10 mg per dose) to minimize risk of anaphylactoid reactions, which occur in approximately 3 per 100,000 doses. 7
• Reassess PT/INR after 12-24 hours and continue daily IV dosing until stable, then transition to high-dose oral maintenance (10 mg daily). 7

Form and Administration

Vitamin K1 (phylloquinone) is the only acceptable form—never use menadione salts. 5, 1

• Oral administration is preferred for maintenance therapy in stable patients. 1
• Intravenous route is reserved for acute bleeding, severe coagulopathy, or when oral absorption is questionable. 6
• Do not use intramuscular injections in PFIC patients with coagulopathy due to hematoma risk. 8

Monitoring Protocol

Monitor PT/INR at baseline, then every 3-6 months during stable maintenance therapy, and more frequently (every 1-2 weeks) after dose adjustments or during acute illness. 5

• PIVKA-II (protein induced by vitamin K absence) is the most sensitive marker for subclinical deficiency and should be measured when available, particularly if bleeding occurs despite apparently adequate dosing. 9, 7
• Regular monitoring is essential because PFIC patients can develop sudden severe deficiency even on maintenance therapy, especially during intercurrent illness or if medication adherence lapses. 6

Critical Pitfalls to Avoid

Never assume that normal dietary intake or standard supplementation doses (1-2 mg daily) are adequate for PFIC patients—they require higher doses due to severe malabsorption. 5, 2

• Do not use infant dosing (0.3-1 mg daily) for school-age children with PFIC, as this is grossly insufficient. 1
• Do not wait for confirmatory coagulation studies before administering IV vitamin K in a PFIC patient with active bleeding—it may be lifesaving. 6
• Cholestyramine, often used for pruritus in cholestatic patients, can worsen vitamin K deficiency and should be separated from vitamin K administration by at least 2 hours. 5
• Monitor medication adherence closely, as missed doses can rapidly lead to severe coagulopathy and life-threatening bleeding within days to weeks. 6

Special Considerations

PFIC patients require lifelong vitamin K supplementation, as the underlying cholestasis persists even after biliary diversion procedures. 3, 2

• Patients awaiting liver transplantation need particularly vigilant monitoring and may require doses at the upper end of the range (10 mg daily). 2
• Vitamin K toxicity is not a concern at any dose within the recommended range (up to 10 mg daily), allowing clinicians to err on the side of adequacy. 5, 1
• During acute illnesses, antibiotic therapy, or perioperative periods, consider temporary increase to 10 mg daily or switch to parenteral administration. 5