What is the difference between Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT)?

Difference Between PT and APTT

PT (Prothrombin Time) and APTT (Activated Partial Thromboplastin Time) are fundamentally different coagulation tests that assess distinct pathways: PT evaluates the extrinsic and common pathways (factors II, V, VII, X, and fibrinogen), while APTT evaluates the intrinsic and common pathways (factors VIII, IX, XI, XII, and the common pathway factors). 1

What Each Test Measures

Prothrombin Time (PT)

• PT measures the extrinsic coagulation pathway, which includes factors VII, X, V, II (prothrombin), and fibrinogen 1
• Normal PT indicates adequate levels of these specific clotting factors in the extrinsic and common pathways 1
• PT is primarily designed and validated to assess coagulation status in patients receiving vitamin K antagonist (VKA) therapy like warfarin 1
• The test is reported as clotting time (seconds), PT ratio (patient-to-normal), or INR (International Normalized Ratio) 2

Activated Partial Thromboplastin Time (APTT)

• APTT measures the intrinsic coagulation pathway, which includes factors XII, XI, IX, VIII, and the common pathway factors (X, V, II, fibrinogen) 3
• APTT is the primary test for monitoring unfractionated heparin therapy 4
• The test is reported as clotting time (seconds) or as a ratio (patient-to-normal clotting time) 2
• APTT is more sensitive to deficiencies in the intrinsic pathway factors compared to PT 3

Clinical Applications and Interpretation

When PT is Primarily Affected

• Direct Factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) predominantly prolong PT more than APTT 4
• Warfarin and other vitamin K antagonists cause PT prolongation by reducing factors II, VII, IX, and X 4
• Liver dysfunction affects PT earlier and more significantly than APTT because factor VII (measured by PT) has the shortest half-life 1
• Factor VII deficiency specifically prolongs PT while leaving APTT normal 1

When APTT is Primarily Affected

• Direct thrombin inhibitors (dabigatran) predominantly prolong APTT more than PT 4
• Unfractionated heparin monitoring relies on APTT, with therapeutic range typically 1.5-2.5 times the baseline 4
• Hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) cause isolated APTT prolongation 5
• Lupus anticoagulant and other circulating anticoagulants typically prolong APTT 5

When Both Are Prolonged

• Disseminated intravascular coagulation (DIC) causes prolongation of both PT and APTT due to consumption of multiple clotting factors 1
• Severe liver disease affects both pathways as the liver synthesizes most coagulation factors 1
• Common pathway factor deficiencies (factors II, V, X, or fibrinogen) prolong both tests 3
• Warfarin at supratherapeutic doses can prolong both PT and APTT 1

Critical Differences in Sensitivity

Reagent Variability

• PT reagents (thromboplastins) have highly variable sensitivity to different anticoagulants, which is why INR was developed for warfarin monitoring but remains invalid for DOACs 4
• APTT reagents also vary significantly in their sensitivity to heparin and dabigatran, with results differing substantially between reagent types 4
• The concentration-response curve for dabigatran's effect on APTT is non-linear at higher concentrations (≥200 ng/mL) 4

Pregnancy-Specific Considerations

• During pregnancy, both PT and APTT are shortened due to increased coagulation factors, especially in the third trimester 4
• PT ratio and APTT ratio ≥1.5 should be used as the cut-off for coagulopathy in pregnancy rather than absolute values in seconds 4
• At 36 weeks gestation, median PT is 9.60 seconds and median APTT is 31.00 seconds 4

Common Pitfalls and Limitations

Screening Limitations

• Neither PT nor APTT should be used as routine preoperative screening tests in asymptomatic patients without clinical bleeding history, as false-positive results greatly outnumber true-positives 3
• A normal APTT has limited value in trauma patients on dabigatran, especially outside peak plasma drug concentration 4
• Normal PT and APTT cannot rule out the presence of DOACs, as therapeutic concentrations may not prolong these tests depending on the reagent used 4

Monitoring Anticoagulation

• INR should never be used to interpret PT results in patients on DOACs, as the INR scale was specifically designed for vitamin K antagonists only 4
• PT/INR are only mildly elevated by dabigatran and are less sensitive than APTT for detecting this drug 4
• APTT can be twofold elevated at peak dabigatran concentration but may still be 1.5 times normal after 12 hours, making timing correlation difficult 4

Diagnostic Algorithm

• If both PT and APTT are normal in a patient with abnormal bleeding, further investigation of the coagulation system is not needed 3
• If one or both tests are prolonged, perform a 50:50 mixing study with normal plasma to distinguish factor deficiency from inhibitors 4
• For isolated PT prolongation: consider factor VII deficiency, early liver disease, or Factor Xa inhibitors 1
• For isolated APTT prolongation: consider hemophilia, von Willebrand disease, heparin therapy, lupus anticoagulant, or dabigatran 5
• For both prolonged: consider common pathway deficiencies, severe liver disease, DIC, or warfarin therapy 1