What is prothrombin time (PT)?

Prothrombin Time (PT): Definition, Purpose, and Clinical Applications

Prothrombin time (PT) is a laboratory test that measures the time it takes for blood to clot through the extrinsic and common coagulation pathways, primarily assessing factors II, VII, and X. 1 It was originally developed by Armand Quick in 1935 to evaluate coagulation defects in patients with jaundice and bleeding tendencies.

Historical Development and Mechanism

The PT test was formally introduced when only four coagulation factors were recognized:

• Fibrinogen (Factor I)
• Prothrombin (Factor II)
• "Thromboplastin" (Factor III)
• Ionic calcium (Factor IV)

The test was named "prothrombin time" because:

• It was believed that clotting time was directly proportional to prothrombin levels
• Other factors in the coagulation cascade were not yet discovered 1

How PT is Measured

PT is measured by:

1. Adding calcium and thromboplastin (tissue factor) to citrated plasma
2. Measuring the time in seconds until clot formation
3. The thromboplastin reagent contains tissue factor and phospholipids that promote activation of Factor X by Factor VII 1

Clinical Applications

PT is primarily used for:

1. Monitoring vitamin K antagonist (VKA) therapy:

   • Most established and validated use of PT
   • Converted to International Normalized Ratio (INR) for standardization
   • Target INR ranges typically 2.0-3.0 or 2.5-3.5 depending on indication 1, 2

2. Other common but less validated uses:

   • Assessing hemorrhagic tendency
   • Predicting procedural bleeding risk
   • Evaluating disease severity (especially liver disease)
   • Prognosticating clinical course
   • Gauging transfusion needs
   • Screening for hemostatic disorders of the extrinsic pathway 1

International Normalized Ratio (INR)

The INR was developed to standardize PT results across different laboratories and thromboplastin reagents:

• Formula: INR = (PT/MNPT)^ISI

  • MNPT = Mean Normal Prothrombin Time
  • ISI = International Sensitivity Index 1

• Purpose: To eliminate variability in PT results due to differences in thromboplastin reagents and laboratory techniques 1

• Important limitation: The INR was specifically designed and validated only for monitoring VKA therapy, not for general coagulation assessment 1

Clinical Interpretation

Normal PT values typically range from 10-13 seconds, though reference ranges may vary by laboratory.

Prolonged PT may indicate:

• VKA therapy (intended effect)
• Liver disease
• Vitamin K deficiency
• Disseminated intravascular coagulation (DIC)
• Factor deficiencies (II, V, VII, X)

Monitoring Considerations

When monitoring VKA therapy:

• PT should be determined daily after initial dose until stabilization in therapeutic range
• Once stable, testing intervals typically range from one to four weeks
• Additional testing is recommended when:
  • Changing between warfarin products
  • Starting, stopping, or changing other medications 2

Common Pitfalls and Limitations

1. INR misapplication: Using INR for purposes other than VKA monitoring lacks clinical evidence and face validity 1

2. Thromboplastin variability: Different thromboplastins have varying sensitivities to coagulation factor deficiencies, which can affect PT results 1

3. Timing considerations: When interpreting PT/INR in patients on direct oral anticoagulants (DOACs), the time between drug administration and blood sampling is crucial 1

4. Inappropriate plasma transfusion: Correcting mildly abnormal INR values in non-bleeding patients without VKA therapy often leads to unnecessary transfusions with potential harms 1

5. Method differences: The Owren PT method has shown advantages over the Quick PT method in harmonization of INR results, with better precision and less variation 3

PT remains a cornerstone test in coagulation assessment, but its interpretation must be contextualized to the specific clinical scenario, particularly distinguishing between VKA-treated patients and other clinical situations.