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

PT vs PTT: Key Differences

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

What Each Test Evaluates

PT Pathway Components

• PT specifically assesses factors VII, X, V, II (prothrombin), and fibrinogen in the extrinsic coagulation pathway 1
• Factor VII has the shortest half-life of all coagulation factors, making PT the earliest indicator of liver dysfunction 1
• Normal PT indicates adequate levels of these specific clotting factors in the extrinsic and common pathways 1

PTT Pathway Components

• PTT evaluates the intrinsic pathway factors (VIII, IX, XI, XII) plus all common pathway factors (I, II, V, X) 1, 2
• PTT assesses a broader range of coagulation factors compared to PT 2

Primary Clinical Applications

When to Use PT

• PT is the validated test for monitoring warfarin and other vitamin K antagonist therapy 1
• PT is reported as INR specifically for patients on vitamin K antagonists—the INR scale was designed exclusively for this purpose and should never be used for other clinical scenarios 1, 3
• Factor VII deficiency causes isolated PT prolongation with normal PTT 1
• Direct Factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) predominantly prolong PT more than PTT 1

When to Use PTT

• PTT is the primary test for monitoring unfractionated heparin therapy, with therapeutic range typically 1.5-2.5 times baseline 1
• Direct thrombin inhibitors (dabigatran, argatroban, lepirudin, bivalirudin) predominantly prolong PTT more than PT 1, 2
• PTT is used to assess patients on direct thrombin inhibitors 2

Differential Diagnosis Based on Test Patterns

Isolated PT Prolongation

• Factor VII deficiency 1
• Early liver disease (factor VII depletes first due to shortest half-life) 1
• Direct Factor Xa inhibitors 1
• Warfarin therapy (early stages) 1

Isolated PTT Prolongation

• Hemophilia A (factor VIII deficiency) or B (factor IX deficiency) 4
• Factor XI or XII deficiency 4
• Unfractionated heparin therapy 1
• Direct thrombin inhibitors 1
• Lupus anticoagulant or other circulating anticoagulants 4

Both PT and PTT Prolonged

• Common pathway deficiencies (factors II, V, X, fibrinogen) 1
• Severe liver disease 1
• Disseminated intravascular coagulation (DIC) 5
• Warfarin therapy (established) 1

Critical Pitfalls to Avoid

INR Misuse

• Never use INR to interpret PT results in patients on direct oral anticoagulants (DOACs)—the INR scale is invalid outside of vitamin K antagonist therapy 1, 3
• INR is a poor predictor of bleeding risk in patients not on vitamin K antagonists 2, 5
• For patients not on warfarin, report PT as ratio (patient-to-normal clotting time) rather than INR 3

Reagent Variability

• PT reagents (thromboplastins) have highly variable sensitivity to different anticoagulants, which is why INR standardization only works for warfarin 1
• PTT reagents vary significantly in their sensitivity to heparin and dabigatran, with results differing substantially between reagent types 1
• The concentration-response curve for dabigatran's effect on PTT is non-linear at higher concentrations (≥200 ng/mL) 1

Pregnancy Considerations

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

Pediatric Limitations

• In infants, PTT does not correspond to anti-Factor Xa levels due to developmental hemostasis 2
• PTT shows poor correlation with heparin levels in children and may be unreliable with elevated Factor VIII, fibrinogen, or presence of antiphospholipid antibodies 2

Diagnostic Algorithm for Prolonged Results

Initial Step for Any Prolongation

• Perform a 50:50 mixing study with normal plasma to distinguish factor deficiency from inhibitors 1
• If mixing study corrects: factor deficiency is present 6
• If mixing study does not correct: inhibitor (antibody or anticoagulant drug) is present 6

Advanced Testing When Needed

• For comprehensive coagulation assessment, especially in trauma or massive bleeding, use thromboelastography (TEG) or rotational thromboelastometry (ROTEM) rather than relying solely on PT/PTT 2
• Low molecular weight heparin should be monitored using anti-Xa activity, not PTT 2
• Direct oral anticoagulants require specific assays such as dilute thrombin time or ecarin clotting time for quantitation 2