Causes of a Significantly Prolonged Partial Thromboplastin Time (PTT)
A significantly prolonged PTT most commonly indicates factor deficiencies of the intrinsic pathway, presence of inhibitors like lupus anticoagulant or factor inhibitors, or the effect of heparin therapy. 1, 2
Common Causes of Prolonged PTT
1. Factor Deficiencies
- Hemophilia A: Factor VIII deficiency 2
- Hemophilia B: Factor IX deficiency 2
- Hemophilia C: Factor XI deficiency 2
- Factor XII deficiency: Usually not associated with bleeding risk 1, 3
2. Inhibitors
- Acquired factor inhibitors: Particularly acquired hemophilia A with autoantibodies against Factor VIII 1
- Lupus anticoagulant: Paradoxically associated with thrombosis rather than bleeding 1, 4, 5
3. Medication Effects
- Heparin therapy: Direct anticoagulant effect 6
- Other anticoagulants: Some direct oral anticoagulants can affect PTT 3
Diagnostic Approach
Step 1: Mixing Studies
Mixing studies help differentiate between factor deficiencies and inhibitors:
- Factor deficiency: PTT corrects when patient plasma is mixed with normal plasma
- Inhibitor presence: PTT remains prolonged after mixing 1
- Time-dependent inhibitors: FVIII inhibitors may show more prolongation after 1-2 hour incubation 1
Step 2: Specific Factor Assays
- Measure levels of factors VIII, IX, XI, and XII when PTT is prolonged 1, 2
- An isolated low factor VIII level suggests acquired hemophilia A 1
- Sometimes all intrinsic factors appear decreased due to in vitro artifact 1
Step 3: Inhibitor Testing
- Bethesda assay: Quantifies factor inhibitors, particularly FVIII inhibitors 1, 2
- Lupus anticoagulant testing: Including dilute Russell's Viper Venom Time (dRVVT) and silica-based aPTT with low phospholipid content 2, 5
- FVIII antibody ELISA: Useful in complex cases to distinguish between lupus anticoagulant and acquired FVIII inhibitor 1
Clinical Significance
Research shows that prolonged PTT may indicate:
- Hemostatic defect: In approximately 50% of cases 7
- No particular risk: In about 36% of cases 7
- Laboratory artifact: In 14% of cases 7
Important Considerations
- The degree of PTT prolongation does not necessarily correlate with bleeding risk 7
- Repeat testing may be necessary as some inhibitors become detectable only after several days 1
- Different PTT reagents have varying sensitivities to factor deficiencies and lupus anticoagulant 2, 3
- Proper sample processing is essential to avoid artifactual prolongation 2
Clinical Management Implications
- For patients with bleeding symptoms, urgent hemostatic treatment may be required, particularly with bypassing agents for acquired hemophilia A 1
- For preoperative patients with unexplained prolonged PTT, further investigation is essential before proceeding with surgery 8, 5
- Patients with lupus anticoagulant without bleeding history generally do not require specific intervention before surgery 5
- Plasma infusion is not routinely indicated for prolonged PTT due to lupus anticoagulant 5
Remember that the cause of an abnormal PTT is more important than the degree of prolongation when assessing hemostatic risk 7. Close collaboration between clinicians and laboratory staff is crucial for proper diagnosis and management.