How to Check Vitamin K Status
Vitamin K status should be determined by combining a measurement of circulating phylloquinone (vitamin K1) levels in plasma or serum with functional biomarkers, particularly PIVKA-II (undercarboxylated prothrombin), as there is no single gold standard test. 1
When to Measure Vitamin K Status
Measure vitamin K status in at-risk patients, specifically those with: 1
- Pathologies causing steatorrhea (celiac disease, cystic fibrosis, short bowel syndrome) 1
- Prolonged use of broad-spectrum antibiotics 1
- Chronic kidney disease 1
- Malnutrition or restricted diet 1
- Patients on anticoagulant (warfarin) therapy 1
Laboratory Tests to Order
Primary Biomarkers (Use Both)
1. Serum Phylloquinone (Vitamin K1) Level 1
- Measures abundance of vitamin K in circulation 2
- Reflects short-term dietary intake 1
- Deficiency threshold: <0.15 µg/L 1, 2
- Analytical methods include high-pressure liquid chromatography coupled to fluorescence, electrochemical detection, or mass spectrometry 1
- Critical caveat: Samples require special handling to prevent degradation by light exposure, alkaline conditions, and temperature 1
2. PIVKA-II (Protein Induced by Vitamin K Absence/Antagonism-II) 1
- Measures functional vitamin K deficiency by quantifying undercarboxylated prothrombin 1
- Most sensitive homeostatic biomarker of hepatic subclinical vitamin K deficiency 1
- Reference range: 17.4-50.9 mAU/mL (Abbott Architect) 2
- Automated immunoassay using chemiluminescent reaction is available for routine application 1
- Provides retrospective indicator of hepatic vitamin K utilization 2
Why Use Both Tests Together
Using phylloquinone and PIVKA-II in tandem provides insight into both abundance and cellular utilization of vitamin K, which is the recommended approach for most patient cohorts 2. Phylloquinone alone can be falsely reassuring if recent dietary intake occurred, while PIVKA-II reflects actual functional status at the tissue level 2.
Alternative Functional Markers (Less Recommended)
Other vitamin K functional markers have significant limitations but may be used when primary tests are unavailable: 1
- Prothrombin time (PT) or partial thromboplastin time (PTT) - lack sufficient sensitivity and specificity for vitamin K status assessment 2
- Undercarboxylated osteocalcin and matrix γ-carboxyglutamic acid protein - lack established cut-off values 1
- Urinary Gla residues or vitamin K metabolites - not representative of whole-body vitamin K status 1
Important Caveat About PT/INR
Do not use PT or INR as indicators of vitamin K status - these tests are erroneously used for this purpose and lack sensitivity for detecting subclinical deficiency 2. PT/INR is appropriate for monitoring vitamin K antagonist therapy (warfarin), not for assessing nutritional vitamin K status 1, 3. Clinically significant bleeding from vitamin K deficiency typically only occurs in newborns or with extreme malabsorption 1.
Clinical Interpretation Algorithm
- Order both serum phylloquinone and PIVKA-II 1, 2
- If phylloquinone <0.15 µg/L: Indicates vitamin K depletion/deficiency 1, 2
- If PIVKA-II elevated above reference range: Indicates functional vitamin K deficiency with undercarboxylation of clotting factors 1, 2
- Assess dietary intake concurrently, as biomarkers must be interpreted in context of nutrition 1
- Consider response to vitamin K supplementation as confirmatory test if bleeding or prolonged PT is present 1