Mixing Studies in Hematology

Introduction to Mixing Studies

Mixing studies are fundamental diagnostic tests used in pediatric hematology to differentiate between factor deficiencies and the presence of inhibitors when coagulation testing is abnormal.

Key Points

Essential first-line investigation for abnormal coagulation results
Differentiates between factor deficiencies and inhibitors
Crucial for directing further specific factor testing
Cost-effective screening tool

Clinical Applications

Investigation of prolonged PT/PTT
Evaluation of bleeding disorders
Monitoring of anticoagulation therapy
Assessment of acquired inhibitors

Methodology

Procedure Steps:

Collection of patient plasma
Mixing with normal pooled plasma (1:1 ratio)
Immediate testing (Time 0)
Incubation at 37°C for 1-2 hours
Repeat testing post-incubation

Result Interpretation

Pattern Recognition:

Factor Deficiency:
- Immediate correction of abnormal values
- Sustained correction after incubation
- Typically shows >70% correction
Inhibitor Present:
- Initial partial or no correction
- Progressive worsening after incubation
- Less than 50% correction typical

Clinical Pearls

Always perform both immediate and incubated studies
Consider preanalytical variables affecting results
Interpret in context of clinical history
Document timing of any recent factor replacement
Consider lupus anticoagulant in non-bleeding patients

Indications

Unexplained prolongation of PTT/PT
Suspected factor deficiency
Unexplained bleeding
Monitoring of inhibitor development in hemophilia
Pre-operative screening when indicated

Limitations

May miss weak inhibitors
Results affected by recent factor replacement
Requires proper sample handling
Limited utility in mild factor deficiencies
May need repeat testing for confirmation

Pediatric Considerations

Age-specific normal ranges must be considered
Challenging blood collection may affect results
Higher prevalence of transient inhibitors
Development factors affect interpretation

Further Reading