Factor VIII Deficiency Causes Prolonged PTT But Not PT
Factor VIII deficiency causes prolonged partial thromboplastin time (PTT) but not prothrombin time (PT) because Factor VIII is specifically involved in the intrinsic coagulation pathway that is measured by the PTT test, while the PT test measures the extrinsic pathway which does not require Factor VIII. 1
Coagulation Pathway Specificity
Factor VIII functions exclusively within the intrinsic coagulation pathway, which is specifically measured by the PTT test:
- Intrinsic Pathway (measured by PTT): Factor VIII serves as a cofactor for Factor IXa in the activation of Factor X, a critical step in the intrinsic pathway of coagulation 1
- Extrinsic Pathway (measured by PT): This pathway bypasses the need for Factor VIII by activating Factor X directly through the tissue factor-Factor VIIa complex 2
Laboratory Diagnosis of Factor VIII Deficiency
The laboratory profile of Factor VIII deficiency (Hemophilia A) shows:
- Prolonged PTT: Due to impaired intrinsic pathway function
- Normal PT: Because the extrinsic pathway remains intact
- Normal thrombin time: As the final common pathway is not affected 3
This pattern of prolonged PTT with normal PT is the classic laboratory finding that raises suspicion for Factor VIII deficiency, particularly in males with a history of bleeding disorders 4.
Severity Classification and Laboratory Correlation
The severity of Factor VIII deficiency correlates with the degree of PTT prolongation:
| Severity | Factor VIII Activity Level | PTT Prolongation |
|---|---|---|
| Severe | <1% of normal | Markedly prolonged |
| Moderate | 1-5% of normal | Moderately prolonged |
| Mild | >5% to <40% of normal | Mildly prolonged or normal |
Diagnostic Approach
When a prolonged PTT is identified:
Mixing studies are essential to differentiate between factor deficiency and inhibitor presence:
- Complete correction in both immediate and incubated samples indicates factor deficiency
- Initial correction with subsequent prolongation after incubation suggests an inhibitor (typically FVIII autoantibody) 1
Specific factor assays should be performed to confirm the diagnosis:
- Factor VIII:C one-stage assay measures the ability of the patient's plasma to correct the prolonged APTT of Factor VIII-deficient plasma 2
Clinical Implications
The impact of Factor VIII deficiency on coagulation tests has important clinical implications:
- PTT is a reliable screening test for hemophilia A, but may be normal in mild cases (>5% Factor VIII activity) 1
- The degree of PTT prolongation generally correlates with bleeding risk, though not perfectly 5
- Multiple mild factor deficiencies can paradoxically cause more PTT prolongation than expected from a single severe deficiency 6
Common Pitfalls to Avoid
- Relying solely on PTT: Mild Factor VIII deficiency may be missed if only PTT is measured without specific factor assays 7
- Overlooking acquired inhibitors: Factor VIII inhibitors can develop and cause PTT prolongation similar to congenital deficiency 3
- Misinterpreting mixing studies: Proper interpretation of mixing studies is crucial to differentiate between factor deficiency and inhibitors 1
Factor VIII replacement therapy normalizes the PTT by temporarily providing the missing coagulation factor needed for effective hemostasis, confirming the direct relationship between Factor VIII levels and PTT results 5.