Which of the following does not prolong International Normalized Ratio (INR)?

Factor VIII Deficiency Does Not Prolong INR

Factor VIII deficiency does not prolong the International Normalized Ratio (INR) because Factor VIII is part of the intrinsic coagulation pathway, which is not measured by the INR test. 1

Understanding INR and Coagulation Pathways

The INR specifically measures the extrinsic and common coagulation pathways by evaluating the prothrombin time (PT). This test is sensitive to the following factors:

• Factors measured by INR: Factors I (fibrinogen), II (prothrombin), V, VII, and X 1, 2
• Not measured by INR: Factors VIII, IX, XI, and XII (intrinsic pathway factors)

How Each Option Affects INR:

1. Chronic Liver Disease (CLD): Prolongs INR due to decreased synthesis of multiple coagulation factors including II, V, VII, and X 1

2. Vitamin K Deficiency: Prolongs INR because vitamin K is required for the synthesis of functional factors II, VII, IX, and X 1

3. Warfarin: Prolongs INR by inhibiting vitamin K-dependent factors (II, VII, IX, X) 1

4. Factor VIII Deficiency: Does NOT prolong INR because Factor VIII is part of the intrinsic pathway measured by aPTT, not PT/INR 1

5. Factor VII Deficiency: Prolongs INR because Factor VII is a key component of the extrinsic pathway directly measured by PT/INR 1

Clinical Relevance of INR Testing

INR was developed to standardize PT results across different laboratories and reagents, primarily for monitoring oral anticoagulant therapy with vitamin K antagonists like warfarin 2, 3.

• Normal INR range: 0.8-1.2 for individuals not on anticoagulant therapy
• Target INR range: 2.0-3.0 for most patients on warfarin therapy 1

Common Pitfalls in INR Interpretation:

• Assuming all coagulation factor deficiencies affect INR
• Using INR to assess bleeding risk in liver disease without considering the balanced reduction in both pro- and anticoagulant factors 1
• Attempting to "correct" elevated INR in cirrhosis with fresh frozen plasma, which may not improve hemostasis and can worsen portal hypertension 1

Important Clinical Considerations

• In patients with liver disease, INR may be elevated despite a rebalanced hemostatic system due to parallel decreases in anticoagulant factors (especially protein C) 1
• Factor VIII levels are often elevated in liver disease, contributing to a relatively hypercoagulable state despite prolonged INR 1
• Viscoelastic tests may provide better assessment of coagulation status in complex cases than traditional tests like INR 1

Remember that while Factor VIII deficiency (hemophilia A) causes bleeding tendencies, it will show normal PT/INR values but prolonged aPTT results, making it the only option that does not prolong INR.