PT/INR in Factor V Leiden
Yes, PT/INR is normal in patients with Factor V Leiden. Factor V Leiden does not affect the extrinsic or common coagulation pathways measured by PT/INR testing 1, 2.
Why PT/INR Remains Normal
PT/INR measures specific coagulation factors (II, V, VII, X, and fibrinogen) in the extrinsic and common pathways, but Factor V Leiden is a qualitative defect, not a quantitative deficiency 2.
The mutation affects protein C resistance, not factor V levels or PT/INR. Factor V Leiden involves a single point mutation (G1691A) that substitutes glutamine for arginine at position 506, making activated Factor V resistant to inactivation by activated protein C 1.
Factor V is present at normal levels in patients with Factor V Leiden—the protein is simply resistant to degradation by activated protein C, which is not detected by standard PT/INR testing 3, 4.
Appropriate Testing for Factor V Leiden
Direct DNA-based genotyping or Factor V Leiden-specific functional assays are the recommended diagnostic methods, not PT/INR 1.
Modified activated protein C resistance (APC-R) assays using patient plasma diluted in Factor V-deficient plasma provide reliable differentiation between heterozygotes and homozygotes with minimal interference from other clinical factors 1, 3.
Traditional aPTT-based functional tests cast a wider net but lack specificity and are subject to interference from acute phase reactants, pregnancy, oral contraceptives, lupus anticoagulant, heparin, and warfarin therapy 1.
Patients on anticoagulation therapy should proceed directly to molecular testing if modified functional assays are not available, as standard coagulation tests cannot reliably detect Factor V Leiden in these circumstances 1, 3.
Critical Clinical Pitfall
Never use PT/INR as a screening test for Factor V Leiden or other inherited thrombophilias. PT/INR is only validated for monitoring vitamin K antagonist therapy and does not detect qualitative coagulation defects like Factor V Leiden 5, 2.
The INR therapeutic range (2.0-3.0) for anticoagulation applies equally to patients with Factor V Leiden who develop venous thromboembolism, as moderate-intensity anticoagulation is adequate for these patients 1, 6.