What is Prothrombin Time (PT) and how is it done?

Prothrombin Time (PT): Definition and Methodology

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

What is Prothrombin Time?

PT is one of the most commonly used coagulation tests in clinical practice. It was originally developed by Armand Quick in 1935 to evaluate coagulation defects in patients with jaundice and bleeding tendencies 1. The test specifically measures the functionality of the extrinsic and common pathways of the coagulation cascade.

Key aspects of PT:

• Evaluates factors II, VII, and X of the coagulation cascade
• Normal values typically range from 10-13 seconds (though reference ranges vary by laboratory)
• Prolonged PT may indicate:
  • Vitamin K antagonist therapy (e.g., warfarin)
  • Liver disease
  • Vitamin K deficiency
  • Disseminated intravascular coagulation (DIC)
  • Factor deficiencies (II, V, VII, X)

How PT Testing is Performed

The PT assay is performed through the following steps:

1. Blood collection in a citrated tube (sodium citrate anticoagulant)
2. Centrifugation to separate plasma from cellular components
3. Addition of calcium and thromboplastin (tissue factor) to the citrated plasma
4. Measurement of the time in seconds until clot formation 2, 1

The traditional term "thromboplastin" refers to a phospholipid-protein extract of tissue (usually lung, brain, or placenta) that contains both tissue factor and phospholipid necessary to promote activation of factor X by factor VII 2.

International Normalized Ratio (INR)

PT results are often converted to the International Normalized Ratio (INR) to standardize results across different laboratories and thromboplastin reagents. This is calculated using the formula:

INR = (PT/MNPT)^ISI

Where:

• MNPT = Mean Normal Prothrombin Time
• ISI = International Sensitivity Index 2, 1

The ISI reflects the responsiveness of a thromboplastin to warfarin-induced changes in clotting factors. Different thromboplastins have varying sensitivities, which necessitated the development of the INR system 2.

Important Considerations for PT Testing

1. Sample stability: PT testing should ideally be performed within 24 hours of blood collection when samples are stored at room temperature or refrigerated at 4°C 3

2. Standardization challenges: Despite efforts to harmonize results through the INR system, laboratory-reported INR values may still differ, even when using the same thromboplastin reagent and coagulometer 4

3. INR limitations: The INR was specifically designed and validated only for monitoring vitamin K antagonist therapy, not for general coagulation assessment 1

4. Clinical applications: The World Journal of Emergency Surgery recommends performing PT routinely in elderly trauma patients to assess anticoagulant exposure 2

Recent Technological Advances

Newer technologies are emerging that allow for rapid PT/INR testing in whole blood without the need for separation of cellular components, potentially enabling point-of-care or patient self-testing 5.

PT testing remains a cornerstone of coagulation assessment, particularly for monitoring anticoagulant therapy with vitamin K antagonists and evaluating liver function and bleeding disorders.