APTT Screening Test: Assessed Clotting Factors
The correct answer is D (A and B): APTT screens for both the common pathway factors (FX, FV, FII, Fibrinogen) AND the intrinsic pathway factors (FXII, FXI, FIX, FVIII). 1, 2
Mechanistic Basis of APTT
The APTT evaluates the intrinsic and common pathways of coagulation by measuring the activity of factors XII, XI, IX, VIII, X, V, II (prothrombin), and I (fibrinogen). 1 This comprehensive assessment distinguishes it from the PT, which only evaluates the extrinsic pathway (Factor VII) and common pathway. 1
Intrinsic Pathway Factors (Option B)
- FXII, FXI, FIX, FVIII are exclusively assessed by APTT, not by PT 1, 2
- These factors are activated during the preincubation phase with negatively charged materials (kaolin, ellagic acid) 3
- Deficiencies in factors VIII, IX, and XI are clinically significant and reliably detected by APTT 4, 5
- Factor XII deficiency is also detected, though typically asymptomatic 4
Common Pathway Factors (Option A)
- FX, FV, FII, Fibrinogen are assessed by both APTT and PT because they participate in the final common pathway 1, 2
- Mathematical modeling demonstrates that by the time a clot forms in APTT testing, factor II is activated by 4%, factor X by 5% 3
- The most pronounced APTT prolongation is caused by decreased factor X concentration 3
Why FVII (Option C) is Incorrect
Factor VII is not assessed by APTT. 1 FVII belongs exclusively to the extrinsic pathway and is only evaluated by PT testing. 1 The PT assay uses tissue factor to activate factor VII directly, bypassing all intrinsic pathway factors. 1
Clinical Application
When APTT is prolonged, the diagnostic approach follows this algorithm: 2, 6
- Perform 50:50 mixing study to differentiate factor deficiency from inhibitor 2, 6
- If mixing corrects, measure specific factors: VIII, IX, XI, XII for isolated APTT prolongation 2
- If both PT and APTT are prolonged, prioritize common pathway factors (II, V, X) and fibrinogen 2
- Factor activity levels below 20% reliably correlate with bleeding risk 2
Important Caveats
APTT reagent sensitivity varies significantly between commercial systems. 4, 5, 7 Some ellagic acid-based reagents may miss minor factor deficiencies (25-52% activity), while celite-based reagents detect all deficiencies more reliably. 7 This variability affects clinical detection of mild hemophilia and other coagulopathies. 4, 7