aPTT in Factor V Leiden
Yes, the aPTT is normal in patients with Factor V Leiden. Factor V Leiden is a thrombophilic disorder that does not affect the intrinsic coagulation pathway measured by aPTT, and routine aPTT testing will not detect this mutation 1.
Why aPTT Remains Normal
Factor V Leiden involves a specific point mutation (R506Q) in the Factor V gene that makes Factor V resistant to inactivation by activated protein C, but does not affect the quantity or baseline function of Factor V in standard coagulation assays 1.
The aPTT measures the intrinsic and common coagulation pathways (factors XII, XI, IX, VIII, X, V, II, and fibrinogen), and Factor V Leiden patients have normal levels and baseline activity of these factors 2.
Standard aPTT testing cannot distinguish between normal Factor V and the mutant Factor V Leiden variant because both function normally in the absence of activated protein C 1.
Appropriate Testing for Factor V Leiden
The correct test for Factor V Leiden is either DNA-based genotyping or an activated protein C resistance (APC-R) assay, not aPTT 1, 3.
DNA-Based Testing (Preferred Method)
- DNA-based genotyping is the gold standard with sensitivity of 98.8% and specificity of 99.3% 3.
- This method can be performed on patients taking anticoagulants without interference 3.
- DNA testing distinguishes between heterozygotes and homozygotes, which is clinically important since homozygotes have approximately 10-fold higher thrombotic risk 3.
APC-R Functional Assays
- APTT-based APC-R assays with predilution in Factor V-deficient plasma have near 100% sensitivity and specificity for Factor V Leiden mutations 1.
- These assays measure the prolongation of aPTT in response to added activated protein C—Factor V Leiden shows reduced prolongation (resistance) 1.
- Modified APTT-based APC-R with predilution has 82% sensitivity for Factor V Leiden detection 4.
Clinical Implications
- Do not rely on routine coagulation screening (PT, aPTT) to detect Factor V Leiden 5.
- Factor V Leiden testing should be reserved for patients with venous thromboembolism where results may influence recurrence risk assessment and anticoagulation duration decisions 6.
- Avoid reflexive thrombophilia testing in patients with arterial or retinal vascular occlusions without systemic thrombosis history 6.
Common Pitfalls to Avoid
- Do not delay thrombophilia workup because aPTT is normal—this is expected in Factor V Leiden 1.
- Do not order aPTT to screen for Factor V Leiden—it will not detect the mutation and may provide false reassurance 1, 5.
- Avoid functional APC-R assays in patients on direct oral anticoagulants (DOACs)—these can falsely elevate APC-R ratios and miss the diagnosis; use DNA testing instead 1, 3.
- Ensure proper sample collection—improper handling can cause spurious aPTT prolongation unrelated to any coagulation disorder 7.