What other labs should be drawn in a patient on warfarin (Coumadin) with an elevated International Normalized Ratio (INR)?

Evaluating Unexpectedly High INR in a Warfarin Patient

When a patient on warfarin presents with an INR of 8 despite claiming adherence, you should draw a comprehensive hepatic function panel (AST, ALT, alkaline phosphatase, bilirubin, albumin, PT) to assess for liver disease, which can dramatically impair synthesis of vitamin K-dependent clotting factors and amplify warfarin's effect. 1

Primary Laboratory Investigation

Hepatic Function Assessment

• Liver function tests are the single most important additional labs to order, as the INR is a reliable measure of impaired blood coagulation in patients with liver disease 1
• Hepatic dysfunction impairs synthesis of vitamin K-dependent clotting factors (II, VII, IX, X), causing warfarin hypersensitivity even at standard doses 1
• Order: AST, ALT, alkaline phosphatase, total and direct bilirubin, albumin, and PT (in addition to INR) 1

Additional Diagnostic Considerations

Medication reconciliation and drug interaction assessment:

• Review all medications, supplements, and over-the-counter drugs for interactions that potentiate warfarin effect 1
• Common culprits include antibiotics (especially metronidazole, trimethoprim-sulfamethoxazole), antifungals, amiodarone, and NSAIDs 1

Nutritional and dietary assessment:

• Assess for recent changes in vitamin K intake, as dietary fluctuations significantly affect INR stability 1
• Decreased vitamin K intake (from illness, dietary changes, or malabsorption) can cause INR elevation 1
• Consider checking nutritional markers if malnutrition or malabsorption is suspected 1

Thyroid function:

• Hyperthyroidism increases warfarin sensitivity by accelerating catabolism of vitamin K-dependent clotting factors 1
• Consider TSH if clinical suspicion exists 1

Renal function:

• Check creatinine and BUN, as renal failure is a bleeding risk factor that may influence warfarin metabolism 1

Critical Pitfalls to Avoid

Laboratory error must be excluded first:

• Repeat the INR immediately to confirm the result, as improper blood collection technique (underfilled tubes with excess citrate) can spuriously prolong PT/INR 1
• Ensure blood was drawn at least 5 hours after IV heparin bolus, 4 hours after continuous IV heparin cessation, or 24 hours after subcutaneous heparin if patient is receiving concurrent therapy 2
• Verify the sample was collected in 3.2% citrate tubes (not 3.8%), as higher citrate concentrations lead to falsely elevated INR values 1

Consider lupus anticoagulant:

• If the patient has autoimmune disease history, lupus anticoagulants can prolong PT/INR independent of warfarin effect 1
• This is a rare but important cause of misleading INR elevation 1

Immediate Management While Investigating

For INR of 8 without bleeding:

• Immediately withhold warfarin and administer oral vitamin K 5 mg 3
• Monitor for bleeding complications, as the risk increases exponentially with INR >5.0 3
• Recheck INR within 24 hours 3

If active bleeding develops:

• Add 4-factor prothrombin complex concentrate (PCC) 50 U/kg IV plus vitamin K 5-10 mg by slow IV infusion for rapid reversal 3

Investigation Algorithm Summary

1. Immediately repeat INR to exclude laboratory error 1
2. Order hepatic function panel (AST, ALT, alkaline phosphatase, bilirubin, albumin) 1
3. Review complete medication list for drug interactions 1
4. Assess dietary vitamin K intake changes 1
5. Check renal function (creatinine, BUN) 1
6. Consider thyroid function (TSH) if clinically indicated 1
7. Investigate for intercurrent illness that may affect warfarin metabolism 1

The most common causes of unexpectedly high INR despite reported adherence are unrecognized drug interactions, dietary changes, liver dysfunction, and intercurrent illness—not patient non-adherence 1.