Mixing Study Interpretation: Factor Deficiency
The mixing study results indicate a factor deficiency (Answer B). The prolonged PTT that corrects to normal (32 sec, within normal range of 24-37 sec) after mixing with normal plasma definitively indicates the patient lacks one or more coagulation factors, which are supplied by the normal plasma in the mixture. 1, 2, 3
Interpretation Logic
Correction on mixing = Factor deficiency, not inhibitor. By definition, complete correction of the aPTT in a 1:1 mix of patient and reference plasma indicates a factor deficiency rather than an inhibitor. 3 The American Society of Hematology confirms that immediate correction of the aPTT with normal plasma indicates factor deficiency, while failure to correct suggests an inhibitor (lupus anticoagulant or factor inhibitor). 1
Key Findings Supporting Factor Deficiency:
Normal PT (10.0 sec) excludes deficiencies in the extrinsic and common pathways (Factor VII, and common pathway factors like Factor X, V, prothrombin, and fibrinogen when combined with prolonged PTT). 4
Isolated prolonged PTT (50 sec) points to deficiency in the intrinsic pathway factors: Factor VIII, IX, XI, or XII. 1, 5
Post-incubation correction (32 sec) rules out time-dependent inhibitors like Factor VIII autoantibodies, which would show prolongation after incubation compared to immediate mixing. 2
Next Steps in Diagnosis
Perform specific factor assays to identify which intrinsic pathway factor is deficient. Regardless of mixing study results, specific factor assays should be performed to facilitate accurate diagnosis. 2
Most Likely Deficiencies:
Hemophilia A (Factor VIII deficiency) is the most common inherited cause presenting with isolated low Factor VIII activity and immediate correction on mixing studies. 1
Von Willebrand disease presents with low Factor VIII levels and corrects on mixing studies. 1
Hemophilia B (Factor IX deficiency) causes bleeding and corrects on mixing studies. 1
Factor XI deficiency may cause mild bleeding tendency. 5
Critical Pitfall to Avoid:
Do not completely exclude acquired hemophilia A based solely on mixing study correction. The International Society on Thrombosis and Haemostasis notes that immediate correction does not completely exclude acquired hemophilia A, so if clinical bleeding is present, proceed with inhibitor workup (Bethesda assay) regardless. 1, 2 However, in this case with post-incubation correction, acquired hemophilia A is highly unlikely since Factor VIII autoantibodies typically show prolongation after incubation. 2
Additional Considerations
Rule out preanalytical variables before finalizing diagnosis:
Verify no heparin contamination by checking thrombin time or medication history. 1, 5
Consider if patient is on warfarin (though normal PT makes this unlikely). 1, 5
Confirm proper sample collection and processing, as preanalytical variables significantly influence aPTT measurements. 5
Clinical context matters for specific factor identification: