What is the clinical significance and use of Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), International Normalized Ratio (INR), and Activated Clotting Time (ACT) in patient management?

Clinical Significance and Use of PT, APTT, INR, and ACT in Patient Management

The prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), and activated clotting time (ACT) are essential coagulation tests with specific clinical applications, each designed to assess different aspects of the coagulation cascade and monitor specific anticoagulant therapies.

Prothrombin Time (PT) and International Normalized Ratio (INR)

• PT measures the function of the extrinsic and common pathways of coagulation, specifically assessing factors I, II, V, VII, and X 1
• PT is the primary test for monitoring vitamin K antagonist (VKA) therapy such as warfarin 2
• INR was specifically developed to standardize PT results across different laboratories and thromboplastin reagents, primarily for monitoring VKA therapy 1, 3
• The INR is calculated using the patient's PT, mean normal PT, and the international sensitivity index (ISI) of the thromboplastin reagent 3
• Standard therapeutic INR ranges:
  • Most conditions requiring anticoagulation: 2.0-3.0 4
  • Mechanical heart valves: 2.5-3.5 4
• INR should not be used as a general predictor of bleeding risk in patients not on VKA therapy, as it lacks validation for this purpose 1, 5

Activated Partial Thromboplastin Time (APTT)

• APTT evaluates the intrinsic and common pathways of coagulation, specifically assessing factors I, II, V, VIII, IX, X, XI, and XII 1
• Primary test for monitoring unfractionated heparin (UFH) therapy 6
• Sensitivity of APTT depends on reagents used, making standardization between laboratories challenging 7
• UFH therapy is typically monitored to maintain APTT at 1.5-2.5 times the normal control value 6
• APTT may be prolonged by factors other than anticoagulants, including liver disease, consumption of coagulation factors, and hematological disorders 1

Activated Clotting Time (ACT)

• Point-of-care test primarily used in high-dose anticoagulation settings such as cardiac catheterization, cardiac surgery, and extracorporeal procedures 1
• More suitable than APTT for monitoring high-dose heparin therapy 1
• Results available within minutes, allowing for rapid clinical decision-making during procedures 1

Clinical Applications

Monitoring Anticoagulant Therapy

• VKA therapy (e.g., warfarin): Monitor using PT/INR 2
  • INR should be determined daily after initial dose until stabilized in therapeutic range 2
  • Once stable, testing intervals typically range from 1-4 weeks 2
• Unfractionated heparin: Monitor using APTT 6
  • Target APTT is typically 1.5-2.5 times normal control 6
• Low molecular weight heparin (LMWH): Monitor using anti-Xa activity, not APTT 1
• Direct oral anticoagulants (DOACs): Standard coagulation tests have limitations 1
  • Dabigatran (direct thrombin inhibitor): Dilute thrombin time, ecarin clotting time, or ecarin chromogenic assay for quantitation 1
  • Factor Xa inhibitors (apixaban, edoxaban, rivaroxaban): Anti-Xa assay calibrated with the specific drug 1

Bleeding Risk Assessment

• PT/INR alone is a poor predictor of bleeding risk in patients not on VKA therapy 1, 5
• For trauma patients, especially elderly patients on anticoagulants, routine coagulation testing including PT/INR, APTT, and anti-Xa levels is recommended 1
• For emergency neurosurgery, maintaining PT/APTT <1.5 times normal control and platelet count >50×10⁹/L is recommended 5

Conversion Between Anticoagulants

• When converting from heparin to warfarin, overlap therapy for 4-5 days until warfarin has produced the desired PT/INR 2
• When measuring PT/INR in patients receiving both heparin and warfarin, blood should be drawn:
  • At least 5 hours after IV bolus heparin
  • 4 hours after cessation of continuous IV heparin infusion
  • 24 hours after subcutaneous heparin injection 2

Common Pitfalls and Limitations

• INR was designed specifically for monitoring VKA therapy and should not be used as a universal predictor of bleeding risk 1, 5
• Plasma transfusion to correct mildly elevated INR values (1.0-2.0) in patients not on VKA therapy lacks evidence of benefit and may expose patients to unnecessary risks 5
• APTT results can vary significantly between laboratories due to differences in reagent sensitivity 7
• Standard coagulation tests (PT/APTT) have limited utility in assessing DOAC activity; specific assays are preferred when available 1
• In liver disease, INR is a poor predictor of bleeding risk despite its use in prognostic scores 5

Advanced Coagulation Testing

• For more comprehensive assessment of coagulation, especially in trauma or massive bleeding, viscoelastic tests like thromboelastography (TEG) or rotational thromboelastometry (ROTEM) may provide additional information 1, 5
• Quantitative assays for DOACs (anti-Xa levels, dilute thrombin time) should be considered when available, particularly in elderly trauma patients on anticoagulant therapy 1

By understanding the specific applications and limitations of these coagulation tests, clinicians can appropriately select and interpret them to guide anticoagulant therapy and assess bleeding risk in various clinical scenarios.