Do point of contact International Normalized Ratio (INR) testing devices give a lower reading when the INR is high in patients on warfarin (coumarin) therapy?

Point-of-Care INR Devices and High INR Readings

Yes, point-of-care INR testing devices can underestimate INR values when the INR is high, particularly at INR levels ≥4.0, which poses a significant clinical risk by potentially masking dangerous levels of anticoagulation that increase bleeding risk.

Device-Specific Performance Issues at High INR Values

The American Heart Association/American College of Cardiology Foundation guidelines document specific limitations of POC devices at elevated INR ranges:

• The Biotrack 512 (Ciba-Corning) underestimated INR by a mean of 0.76 units compared to reference methods 1
• The Coumatrak (DuPont) was accurate in the therapeutic range of 2.0-3.0 but gave discrepant results at higher INR values 1
• The Ciba-Corning monitor specifically underestimated results when INR was 4.0, though this error could be corrected using a revised ISI value 1

Clinical Significance of the Discrepancy

This underestimation is particularly dangerous because:

• Bleeding risk increases exponentially when INR exceeds the upper therapeutic limit, with sharp increases at INR >4.0 1, 2
• A POC device reading of 3.5 might actually represent a laboratory INR of 4.0 or higher, placing the patient at significantly elevated bleeding risk without appropriate clinical recognition 1
• Recent research confirms that mean differences between POC and laboratory INR increase progressively at high INR ranges, with vitamin K-dependent coagulation factor changes contributing to the discrepancy 3

Mechanism of Discrepancy

The 2023 study comparing CoaguChek XS Plus to conventional laboratory testing revealed:

• Conventional laboratory tests better assess warfarin-induced changes in coagulation factors compared to POC devices 3
• Vitamin K-dependent coagulation and anticoagulation factor decreases explain the significant discrepancy between methods in high INR ranges 3
• Endogenous thrombin potential levels showed that conventional laboratory methods (ACL TOP 750) performed better in assessing thrombin changes 3

Clinical Recommendations

When to Confirm with Laboratory Testing

Always obtain confirmatory laboratory INR testing when:

• POC INR reads ≥3.5-4.0, as the true INR may be significantly higher 1, 3
• Clinical bleeding occurs despite "therapeutic" POC readings 1
• Dose adjustments are being considered based on elevated POC values 3

Device Variability Considerations

Different POC devices show varying degrees of accuracy:

• ProTIME Monitor showed better correlation with reference laboratories (r=0.93 for venous samples, r=0.91 for patient finger-stick) 1
• Avocet PT 1000 demonstrated good correlation (r=0.96-0.97) with reference laboratory values 1
• CoaguChek monitors were only slightly less accurate than conventional methods in the best clinical laboratories when used within therapeutic ranges 1

Common Pitfalls to Avoid

Critical Error: Relying Solely on POC at High Values

• Never make clinical decisions about holding warfarin or administering vitamin K based solely on POC readings ≥4.0 without laboratory confirmation 3
• The difference between POC and laboratory INR of 0.4-0.5 units may seem small but can represent the difference between therapeutic (INR 3.0) and high bleeding risk (INR 3.5-4.0) 1, 2

Special Populations Requiring Extra Caution

Patients with antiphospholipid antibody syndrome (APS):

• 8% of APS patients with elevated anti-beta2glycoprotein I levels and positive lupus anticoagulants had non-measurable ProTime INR results 4
• Hemochron Signature devices showed generally higher INR results than plasma-based methods in this subset 4
• Alternative monitoring methods should be used for APS patients when POC devices fail or show discrepant results 4

Practical Algorithm for High INR Management

When POC INR reads 3.5-4.0:

1. Obtain immediate laboratory confirmation 3
2. Hold warfarin dose pending laboratory result 2
3. Assess for bleeding risk factors 2

When POC INR reads 4.0-6.0:

1. Obtain stat laboratory INR 3
2. Assume true INR may be 0.5-1.0 units higher 1, 3
3. Initiate bleeding precautions immediately 2

When POC INR reads >6.0:

1. Treat as potential INR >7.0 until laboratory confirmation 1
2. Consider oral vitamin K 3-5 mg if no active bleeding 2
3. Obtain laboratory INR within 1-2 hours 3

Quality Assurance Considerations

• POC devices require proper calibration with ISI values specific to the instrument and reagent combination 1
• External quality control testing should be performed regularly 1
• Differences between POC and laboratory INR >0.5 units warrant investigation of device accuracy 1, 3