Coagulation Tests: PT and APTT

Introduction to Coagulation Pathways

The American College of Cardiology acknowledges that 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

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
APTT is the primary test for monitoring unfractionated heparin therapy 2

Direct Factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) predominantly prolong PT more than APTT 3, 4
Warfarin and other vitamin K antagonists cause PT prolongation by reducing factors II, VII, IX, and X 2
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
Direct thrombin inhibitors (dabigatran) predominantly prolong APTT more than PT 3, 4
Unfractionated heparin monitoring relies on APTT, with therapeutic range typically 1.5-2.5 times the baseline 2

PT reagents (thromboplastins) have highly variable sensitivity to different anticoagulants, which is why INR was developed for warfarin monitoring but remains invalid for DOACs 5, 6
APTT reagents also vary significantly in their sensitivity to heparin and dabigatran, with results differing substantially between reagent types 5, 7
The concentration-response curve for dabigatran's effect on APTT is non-linear at higher concentrations (≥200 ng/mL) 5, 3

During pregnancy, both PT and APTT are shortened due to increased coagulation factors, especially in the third trimester 8, 9
PT ratio and APTT ratio ≥1.5 should be used as the cut-off for coagulopathy in pregnancy rather than absolute values in seconds 8, 9
At 36 weeks gestation, median PT is 9.60 seconds and median APTT is 31.00 seconds 8

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 5, 3
PT/INR are only mildly elevated by dabigatran and are less sensitive than APTT for detecting this drug 5, 3
APTT can be twofold elevated at peak dabigatran concentration but may still be 1.5 times normal after 12 hours, making timing correlation difficult 5, 3
If one or both tests are prolonged, perform a 50:50 mixing study with normal plasma to distinguish factor deficiency from inhibitors 10
For isolated PT prolongation: consider factor VII deficiency, early liver disease, or Factor Xa inhibitors 1
For both prolonged: consider common pathway deficiencies, severe liver disease, DIC, or warfarin therapy 1