Strictly speaking, an isolated elevation in prothrombin time (PT) with normal activated partial thromboplastin time (aPTT) reflects a defect in the extrinsic pathway, and factor VII deficiency is the only true isolated cause.
Core Principle:
- PT measures: Factors I (fibrinogen), II (prothrombin), V, VII, and X
- aPTT measures: Factors I, II, V, VIII, IX, X, XI, XII
- Only factor VII is exclusive to the PT (extrinsic) pathway
It follows that:
- Isolated PT prolongation = Factor VII abnormality (either deficiency or inhibition).
Practically speaking, a prolonged PT with normal aPTT may also result from::
- Early vitamin K deficiency
- Factor VII is first to fall due to its short half-life
- Warfarin therapy (early)
- Depletes factor VII faster than others
- Liver disease
- Factor VIII is not made in the liver; it’s produced by endothelial cells
- In advanced liver disease, FVIII levels may remain normal or rise (due to inflammation or endothelial activation)
- So while PT (sensitive to FVII and the common pathway) prolongs, aPTT may be less affected or normal because elevated FVIII counteracts deficiencies in other intrinsic pathway factors (like IX, XI)
- Disseminated intravascular coagulation:
- Consumption of multiple clotting factors → prolongs both PT and aPTT
- BUT FVIII is an acute-phase reactant → levels can be elevated in early or compensated DIC
- This may mask aPTT prolongation (by masking deficiencies in other intrinsic pathway factors), making it appear disproportionately normal compared to the PT
A single-institution retrospective study of causes of prolonged prothrombin time and activated partial thromboplastin time in the outpatient setting” (Hazim et al., Int J Lab Hematol, 2022)
- Isolated Prolonged PT (with normal aPTT):
- Total patients: 27 out of 77 (35% of those with persistent abnormalities)
- Acquired causes (22% of total cohort):
- Vitamin K deficiency – 8 patients
- Liver disease (affecting factor VII synthesis) – 4 patients
- Anticoagulation therapy effect – 4 patients (likely warfarin)
- Multiple factor deficiency (e.g., myelodysplastic syndrome) – 1 patient
- Congenital causes (13% of total cohort):
- Factor VII deficiency – 9 patients
- Factor V deficiency – 1 patient
- Clinical pearls:
- Vitamin K deficiency was the most common acquired cause of isolated PT prolongation.
- Factor VII deficiency was the most common congenital cause, consistent with the understanding that PT is exclusively sensitive to FVII.
- Mild liver disease may present with isolated PT prolongation due to the short half-life of FVII.
- Mixing studies were not routinely performed for mild PT prolongation (<14 s) because they nearly always corrected.