What does an activated protein C resistance ratio of 2.6 (reference > 2.3) indicate about factor V Leiden thrombophilia?

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Interpretation of Activated Protein C Resistance Ratio of 2.6

An activated protein C resistance (APC-R) ratio of 2.6 with a reference range >2.3 indicates a NORMAL result, meaning Factor V Leiden mutation is unlikely and the patient does not have resistance to activated protein C. 1

Understanding the Test Result

Normal vs. Abnormal Values

  • The APC-R ratio measures how well activated protein C can inhibit coagulation in the patient's plasma. 1
  • A ratio >2.3 is considered normal, indicating adequate response to activated protein C. 1
  • Your result of 2.6 falls ABOVE the cutoff threshold, placing it in the normal range. 1
  • Lower ratios (typically <2.0-2.3, depending on the assay) indicate APC resistance and suggest Factor V Leiden mutation. 1, 2

What This Means Clinically

Factor V Leiden is unlikely:

  • The most common cause of inherited APC resistance is the Factor V Leiden mutation (Arg506Gln), which accounts for the vast majority of APC-R cases. 1, 3
  • Your normal ratio effectively excludes this mutation with high sensitivity and specificity when using modern predilution assays. 1, 4

Thrombotic risk implications:

  • Factor V Leiden heterozygotes have approximately 4-7 fold increased risk of venous thromboembolism (VTE), while homozygotes have 9-80 fold increased risk. 5
  • With a normal APC-R ratio, you do not have this inherited thrombophilic risk factor. 2
  • The link between APC resistance and arterial stroke is tenuous in adults, though it may play a larger role in cerebral venous thrombosis (CVT) with an odds ratio of 3.38. 1

Important Caveats About the Test

Assay-Specific Considerations

  • Modern predilution assays (where patient plasma is diluted in Factor V-deficient plasma) have near 100% sensitivity and specificity for Factor V Leiden mutations. 1, 4
  • First-generation undiluted APTT-based assays had only 50-86% sensitivity and were prone to interference from lupus anticoagulants, elevated Factor VIII, pregnancy, oral contraceptives, and low protein S levels. 1, 6
  • If your test was performed using a predilution method (most modern laboratories use this), the result is highly reliable. 1

When Further Testing May Be Needed

Molecular DNA testing for Factor V Leiden is NOT indicated with your normal result unless:

  • You have a strong personal history of unprovoked VTE at young age (<50 years). 2
  • You have recurrent thrombotic events despite a normal APC-R ratio. 2
  • There is a documented family history of Factor V Leiden with high-risk clinical situations. 5

Acquired APC Resistance

  • Acquired APC resistance can occur without Factor V mutations and represents an independent risk factor for venous thrombosis. 1
  • However, your normal ratio of 2.6 indicates you do not have clinically significant acquired APC resistance either. 1

Clinical Bottom Line

Your result of 2.6 (above the >2.3 threshold) is reassuring and indicates normal activated protein C function, effectively ruling out Factor V Leiden thrombophilia as a cause of any thrombotic concerns. 1, 2 No further testing for this specific thrombophilic disorder is warranted based on this result alone. 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Factor V Leiden thrombophilia.

Genetics in medicine : official journal of the American College of Medical Genetics, 2011

Guideline

Inheritance Risk of Factor V Leiden from Mother to Child

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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