What is the recommended dose of vitamin K1 (phytonadione) for acute liver injury?

Vitamin K Dosing in Acute Liver Injury

In acute liver injury, administer vitamin K1 (phytonadione) 5-10 mg intravenously as a single dose, though evidence shows limited efficacy in correcting coagulopathy when hepatic synthetic function is severely impaired. 1, 2

Route and Dosing Specifics

• Intravenous administration is strongly preferred over subcutaneous or oral routes in acute liver injury, as intestinal absorption of vitamin K is unreliable in severe hepatic dysfunction 3
• The standard dose is 5-10 mg IV administered slowly (not to exceed 10 mg per dose) 1
• Subcutaneous vitamin K does not modify coagulation parameters in liver disease and should be avoided 2, 4
• Oral administration has an 80% failure rate in severe acute liver disease compared to only 6% with IV administration 3

Critical Understanding of Limited Efficacy

The key clinical reality is that vitamin K has minimal to no effect on coagulopathy in acute liver injury when hepatic synthetic function is impaired. This is fundamentally different from vitamin K deficiency or warfarin reversal. 2, 4

• Vitamin K only works if the liver can synthesize clotting factors—it provides the cofactor but cannot compensate for failed hepatic synthesis 4
• A single 10 mg dose of subcutaneous vitamin K1 failed to improve Factor VII, protein C, or protein S levels in patients with cirrhosis and hepatocellular carcinoma 4
• In severe acute liver dysfunction, only 27% of patients have subclinical vitamin K deficiency that would respond to supplementation 3

When Vitamin K Is Appropriate

Vitamin K should be given in specific clinical scenarios:

• Cholestatic liver disease: Parenteral vitamin K is recommended for jaundiced patients or those with cholestatic pathology, where fat malabsorption may cause true vitamin K deficiency 2
• Excluding vitamin K deficiency: A single dose helps differentiate true deficiency from hepatic synthetic failure 3
• Before invasive procedures: May be considered on a case-by-case basis when local hemostasis is not possible, though efficacy remains limited 2

What NOT to Do

• Do not give repeated daily doses of high-dose vitamin K in cirrhosis—studies show minimal clinical impact with only 0.3 INR reduction over 3 days 5
• Do not routinely correct elevated INR with vitamin K in the absence of active bleeding, as this is not supported by evidence 2
• Do not use vitamin K doses exceeding 10 mg, as higher doses can create a prothrombotic state and prevent re-anticoagulation for days 1

Alternative Management for Active Bleeding

For clinically significant bleeding in acute liver injury, vitamin K alone is insufficient:

• Prothrombin complex concentrate (PCC) provides more rapid and effective correction than fresh frozen plasma, though this is off-label use in liver failure 2
• Targeted blood product replacement should be considered rather than relying on vitamin K 2
• Fresh frozen plasma requires large volumes and carries risks of transfusion-associated circulatory overload 1

Important Safety Considerations

• Anaphylactoid reactions can occur with IV vitamin K1 administration (3 per 100,000 doses), potentially causing bronchospasm and cardiac arrest 1
• Administer IV vitamin K by slow injection to minimize this risk 2
• The reaction is non-IgE mediated, possibly due to the solubilizer in the vitamin K solution 1

Factors Associated with Poor Response

Even when vitamin K is given, certain factors predict treatment failure:

• Higher body weight 5
• Presence of cirrhosis 5
• Higher bilirubin levels 2
• Severe hepatic synthetic dysfunction 4, 3