What is the purpose of a Vitamin K (Vit K) challenge?

From the Guidelines

The Vitamin K challenge test should be performed by administering 10 mg of vitamin K1 (phytonadione) intravenously, as this route allows for a more predictable and rapid reduction in INR compared to oral or subcutaneous administration, as noted in the 2020 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants 1.

Key Considerations

• The test is used to assess liver function by measuring the body's response to vitamin K administration, with a significant improvement in prothrombin time (PT) indicating that the coagulation defect is due to vitamin K deficiency rather than severe liver damage.
• Baseline PT should be measured, followed by vitamin K administration, with a follow-up PT measurement 24 hours later, as the onset of effect of vitamin K depends on the route of administration and the dose given, as stated in the 2020 ACC/AHA guideline for the management of patients with valvular heart disease 1.
• The distinction between coagulopathy caused by vitamin K deficiency and that caused by severe liver dysfunction is crucial, as vitamin K deficiency can be easily corrected with supplementation, while liver dysfunction requires different management approaches.

Administration and Monitoring

• Vitamin K is a cofactor for hepatic production of factors II, VII, IX, and X, and supplementation can quickly restore clotting function if the liver is healthy enough to synthesize these factors, as explained in the 2020 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants 1.
• The dose of vitamin K should be predicated on the presence of active bleeding, the maintenance dose of the VKA, the magnitude of INR elevation, and the desired range into which to reduce the INR, as recommended in the 2020 ACC/AHA guideline for the management of patients with valvular heart disease 1.
• A 10-mg intravenous dose is recommended for life-threatening bleeding, and slow intravenous administration (in 25 to 50 mL normal saline over 15 to 30 minutes) effects a more predictable and rapid reduction in the INR, as noted in the 2020 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) aqueous dispersion of vitamin K1 for parenteral injection, possesses the same type and degree of activity as does naturally-occurring vitamin K, which is necessary for the production via the liver of active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX), and Stuart factor (factor X). The Vitamin K challenge is not directly addressed in the provided drug label.

• The label discusses the mechanism of action of vitamin K and its role in the production of clotting factors.
• It also mentions the pharmacological action of vitamin K in deficient individuals and its use in the prophylaxis and treatment of hemorrhagic disease of the newborn. However, there is no information that directly supports the answer to the question about the Vitamin K challenge. 2

From the Research

Vit K Challenge

• The use of vitamin K for warfarin reversal is a common practice, with intravenous vitamin K1 being recommended for procedures that can be delayed for six to 12 hours 3.
• Vitamin K1 results in the activation of existing clotting factors, allowing for a relatively rapid onset of action, with reversal of anticoagulation occurring within six to 12 hours 3.
• In cases where surgery cannot be delayed, prothrombin complex concentrates (PCCs) should be given, and intravenous vitamin K1 should be infused concurrently to ensure sustained reversal of anticoagulation 3.

Comparison with Other Reversal Agents

• PCCs have been shown to be more effective than fresh frozen plasma (FFP) in achieving rapid INR correction and reducing all-cause mortality 4.
• PCCs also result in a shorter time to INR correction and are associated with a lower risk of post-transfusion volume overload compared to FFP 4.
• The use of PCCs has been found to be an effective treatment modality for the correction of warfarin anticoagulation in the urgent setting, with advantages over FFP including more timely correction and absence of volume overload 5.

Clinical Guidelines

• The selection of the appropriate reversal agent is important to reduce unnecessary complications of treatment and to achieve optimal reversal of anticoagulation 3.
• Evidence-based treatment guidelines are needed to optimize the use of PCCs for warfarin reversal, with consideration of the benefits and risks of each reversal agent 6.
• The use of PCCs in the management of microvascular bleeding should be limited to very specific indications and should not be indicated in the routine management of massive blood loss 7.