Acquired Hemophilia A from Maternal Autoantibodies (Option D)
The most likely diagnosis is acquired hemophilia A caused by transplacentally transferred maternal autoantibodies (Option D), as the failure of the aPTT to correct on mixing study definitively indicates the presence of an inhibitor rather than a simple factor deficiency, which is the hallmark diagnostic finding of acquired hemophilia A. 1, 2
Diagnostic Reasoning
Why the Mixing Study is Decisive
- A prolonged aPTT that fails to correct after mixing with normal plasma indicates the presence of an inhibitor (autoantibody) rather than simple factor deficiency, which is pathognomonic for acquired hemophilia A 1, 2
- The failure to correct with a Rosner index ≥11% specifically points to an inhibitory substance blocking factor activity 1
- In contrast, congenital factor VIII deficiency (hemophilia A, Option A) would show immediate correction of the aPTT when mixed with normal plasma, as the normal plasma supplies the missing factor 3
Clinical Presentation Supports Acquired Hemophilia A
- Spontaneous soft tissue bleeding and hemarthrosis in a neonate are classic manifestations of severe factor deficiency or inhibitor presence 1
- The normal platelet count and normal PT exclude platelet disorders (Option B - Bernard-Soulier syndrome) and extrinsic pathway defects 2
- Neonatal alloimmune thrombocytopenia (Option C) is excluded by the normal platelet count 2
Mechanism in Neonates
- In neonates with transplacentally acquired maternal autoantibodies, maternal IgG antibodies against factor VIII cross the placenta and cause acquired hemophilia A 1
- This condition is typically self-limited as maternal IgG is cleared over 2-3 months, distinguishing it from congenital hemophilia 1
Confirmatory Testing Required
- Measure factor VIII activity level immediately, which will be reduced in acquired hemophilia A 1, 2
- Perform Bethesda assay to quantify the factor VIII inhibitor titer, though it may underestimate autoantibody potency due to type 2 kinetics 1, 2
- Consider factor VIII antibody ELISA if results are ambiguous or to distinguish from lupus anticoagulant 2
Critical Management Considerations
- Immediate hemostatic control is the priority using bypassing agents (recombinant activated factor VII or activated prothrombin complex concentrate) if active bleeding is present 1, 2
- Avoid factor VIII replacement therapy as it will be neutralized by the inhibitor and may boost antibody titers 1
Common Pitfall to Avoid
- Do not confuse this with congenital hemophilia A (Option A) - the key distinguishing feature is that congenital factor VIII deficiency would correct on mixing studies, whereas acquired hemophilia A with inhibitors does not correct 2, 3
- Age-appropriate reference ranges must be considered when interpreting coagulation studies in neonates, as developmental hemostasis causes physiological differences in hemostatic protein concentrations 4