What is the most likely diagnosis for a full-term neonate presenting with spontaneous soft tissue bleeding and joint swelling suggestive of hemarthrosis, with a normal platelet count, normal prothrombin time (PT), prolonged activated partial thromboplastin time (aPTT), and failure of aPTT to correct after mixing with normal plasma?

Diagnosis: Acquired Hemophilia A from Maternal Autoantibodies

The most likely diagnosis is D. Maternal autoantibodies leading to acquired hemophilia, as the failure of aPTT to correct on mixing study indicates the presence of an inhibitor (autoantibody) rather than a simple factor deficiency, which is the hallmark laboratory finding distinguishing acquired hemophilia A from congenital factor deficiencies. 1, 2

Laboratory Pattern Analysis

The clinical presentation demonstrates the classic triad for acquired hemophilia A:

• Prolonged aPTT with failed mixing study correction is pathognomonic for an inhibitory substance (autoantibody) rather than factor deficiency, as factor deficiencies would correct when mixed with normal plasma 1, 2
• Normal PT and normal platelet count exclude extrinsic pathway defects and platelet disorders (eliminating options B and C) 2
• Spontaneous soft tissue bleeding and hemarthrosis in a neonate with this laboratory pattern indicates transplacentally transferred maternal autoantibodies against factor VIII 1, 3

Why Not the Other Options

Factor VIII Deficiency (Option A) - Incorrect

• Congenital hemophilia A (factor VIII deficiency) would show correction on mixing studies because adding normal plasma provides the missing factor 1, 2
• The non-correcting mixing study definitively rules out simple factor deficiency 1
• Hemarthrosis is common in severe congenital hemophilia but occurs rarely in acquired hemophilia A 3, 4

Bernard-Soulier Syndrome (Option B) - Incorrect

• This platelet function disorder would present with thrombocytopenia and prolonged bleeding time, not isolated prolonged aPTT 5
• The normal platelet count excludes this diagnosis 2

Neonatal Alloimmune Thrombocytopenia (Option C) - Incorrect

• Would present with low platelet count, not normal platelets 2
• Does not cause prolonged aPTT 6

Diagnostic Confirmation Required

Immediate next steps to confirm acquired hemophilia A:

• Factor VIII activity level measurement will be reduced 1, 2
• Bethesda assay to quantify the factor VIII inhibitor titer, though it may underestimate autoantibody potency due to type 2 kinetics 1, 2
• Lupus anticoagulant testing to exclude this alternative cause of non-correcting mixing studies 1, 2
• Factor VIII antibody ELISA if results are ambiguous 2

Critical Management Considerations

This is a life-threatening emergency requiring immediate intervention:

• Immediate hemostatic control using bypassing agents (recombinant activated factor VII at 90 μg/kg every 2-3 hours or activated prothrombin complex concentrate at 50-100 IU/kg every 8-12 hours) 1, 2
• Fatal bleeding occurs in 9-31% of acquired hemophilia A cases, with deaths from gastrointestinal, pulmonary, intracranial, and retroperitoneal hemorrhages 1
• In neonates with maternally transferred antibodies, the condition typically resolves as maternal antibodies clear, but acute bleeding control remains the immediate priority 1, 7

Common Pitfall

The key diagnostic error would be assuming this is congenital hemophilia A based on the bleeding pattern and proceeding with factor VIII replacement, which would be ineffective in the presence of inhibitory antibodies 1, 3. The non-correcting mixing study is the critical distinguishing feature that mandates consideration of acquired hemophilia A 1, 2, 8.