What is the difference between prothrombin time (PT) and activated partial thromboplastin time (aPTT)?

Prothrombin Time vs. Activated Partial Thromboplastin Time

PT measures the extrinsic and common coagulation pathways (factors II, V, VII, X, and fibrinogen), while aPTT measures the intrinsic and common pathways (factors VIII, IX, XI, XII, and the common pathway factors). 1

Fundamental Pathway Differences

PT evaluates the extrinsic pathway:

• Specifically assesses factors VII, X, V, II (prothrombin), and fibrinogen 1
• Uses tissue factor (thromboplastin) as the activator with high phospholipid concentrations 2
• Factor VII has the shortest half-life, making PT more sensitive to early liver dysfunction 1

aPTT evaluates the intrinsic pathway:

• Measures factors VIII, IX, XI, XII, plus all common pathway factors (I, II, V, X) 2, 1
• Uses contact activation (kaolin, celite, or ellagic acid) with lower phospholipid concentrations 2
• More sensitive to heparin and lupus anticoagulants due to lower phospholipid content 2

Primary Clinical Applications

PT/INR is the gold standard for:

• Monitoring vitamin K antagonist (warfarin) therapy exclusively 2, 1
• The INR was specifically designed and validated only for VKA monitoring, not as a universal bleeding predictor 1, 3
• Detecting factor VII deficiency (isolated PT prolongation with normal aPTT) 1
• Assessing direct Factor Xa inhibitors (rivaroxaban, apixaban, edoxaban), which predominantly prolong PT more than aPTT 1

aPTT is the primary test for:

• Monitoring unfractionated heparin therapy, with therapeutic range typically 1.5-2.5 times baseline 2, 1
• Detecting direct thrombin inhibitors (dabigatran, argatroban, lepirudin), which predominantly prolong aPTT more than PT 2, 1
• Screening for hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) 1
• Detecting lupus anticoagulant, though baseline PT is rarely prolonged in these patients 2

Critical Sensitivity Differences

PT reagent variability:

• Thromboplastin reagents have highly variable sensitivity to different anticoagulants 1
• The ISI (International Sensitivity Index) corrects for this variability, but only for warfarin monitoring 2, 4
• INR is formally invalid for direct oral anticoagulants (DOACs), liver disease, or general bleeding risk assessment 2, 1, 5

aPTT reagent variability:

• Different aPTT reagents show substantial variation in sensitivity to heparin and dabigatran 1
• The concentration-response curve for dabigatran is non-linear at higher concentrations (≥200 ng/mL) 1
• In infants, aPTT does not correspond to anti-Factor Xa levels due to developmental hemostasis 2

Diagnostic Interpretation Patterns

Isolated PT prolongation suggests:

• Factor VII deficiency (shortest half-life among coagulation factors) 1
• Early liver disease (factor VII depleted first) 1
• Direct Factor Xa inhibitor therapy 1
• Early vitamin K deficiency or warfarin effect 1

Isolated aPTT prolongation suggests:

• Unfractionated heparin therapy 1
• Direct thrombin inhibitor therapy 1
• Hemophilia A or B (factors VIII or IX deficiency) 1
• Lupus anticoagulant 2
• Factor XI or XII deficiency 1

Both PT and aPTT prolonged together indicates:

• Common pathway deficiencies (factors II, V, X, or fibrinogen) 1
• Severe liver disease (>70% synthetic function loss required) 6
• Disseminated intravascular coagulation (DIC) 3
• Vitamin K deficiency or warfarin effect (depletes factors II, VII, IX, X) 6
• Combined anticoagulant therapy 3

Common Clinical Pitfalls

Do not use INR for non-warfarin scenarios:

• INR lacks validity for DOACs, liver disease, DIC, or acute bleeding assessment 2, 1, 5
• Point-of-care INR devices should never be used in patients on NOACs 2
• Pre-procedural INR shows weak or no association with bleeding in 78 of 79 studies reviewed 3

Do not rely solely on PT/aPTT for bleeding risk:

• These tests monitor only the initiation phase (first 4% of thrombin production) 3
• Standard coagulation screens can appear completely normal while overall coagulation remains abnormal 3
• Consider viscoelastic testing (TEG/ROTEM) for comprehensive assessment in trauma or massive bleeding 1, 3

Recognize monitoring limitations:

• aPTT shows poor correlation with heparin levels in children 2
• In patients with high factor VIII or fibrinogen (acute phase reactants), aPTT may not reflect true heparin effect 2
• Low molecular weight heparin does not affect aPTT; use anti-Factor Xa levels instead 2

Special Population Considerations

Pregnancy-specific changes:

• Both PT and aPTT are shortened due to increased coagulation factors, especially in third trimester 1
• Use PT ratio and aPTT ratio ≥1.5 as coagulopathy cut-off rather than absolute values in seconds 1
• At 36 weeks gestation, median PT is 9.60 seconds and median aPTT is 31.00 seconds 1

Lupus anticoagulant patients:

• Baseline PT rarely prolonged due to high phospholipid concentrations in PT reagents 2
• aPTT more sensitive to lupus anticoagulant interference 2
• PT-INR generally unaffected by lupus anticoagulant when monitoring warfarin therapy 2
• Phospholipid composition varies among reagents, so generalization is difficult 2