Diagnosis: Maternal Autoantibodies Leading to Acquired Hemophilia A
The most likely diagnosis is maternal autoantibodies leading to acquired hemophilia A, as the failure of aPTT to correct on mixing studies indicates the presence of an inhibitor rather than a factor deficiency.
Diagnostic Reasoning
Laboratory Pattern Analysis
The clinical presentation demonstrates a classic pattern for acquired hemophilia A rather than congenital factor deficiencies:
- Prolonged aPTT with failed mixing study correction is the hallmark finding that distinguishes acquired hemophilia A from congenital hemophilia 1
- The mixing test failure indicates an inhibitory substance (autoantibody) rather than simple factor deficiency, as factor deficiencies would correct when mixed with normal plasma 1
- Normal platelet count and normal PT exclude platelet disorders (Bernard-Soulier syndrome, neonatal alloimmune thrombocytopenia) and extrinsic pathway defects 2
Why Not Factor VIII Deficiency (Hemophilia A)?
Factor VIII deficiency (congenital hemophilia A) would show aPTT correction on mixing studies because adding normal plasma provides the missing factor 1. The key distinguishing feature here is:
- In congenital hemophilia: mixing study corrects immediately because you're simply replacing the missing factor 1
- In acquired hemophilia: mixing study fails to correct because autoantibodies neutralize the factor VIII in the normal plasma 1
The guideline explicitly states: "Prolongation of the aPTT in a mixture of patient and normal plasma after a 1-2 h incubation compared to an immediate mix is typical of FVIII autoantibodies" 1
Clinical Context Supporting Acquired Hemophilia A
- Neonatal presentation with spontaneous bleeding and hemarthrosis in the setting of maternal autoantibodies is consistent with transplacentally transferred anti-factor VIII antibodies 3, 4
- Acquired hemophilia A characteristically presents with spontaneous soft tissue bleeding, though hemarthrosis is less common than in congenital hemophilia 5
- The postpartum/neonatal period is a recognized time for acquired hemophilia A manifestation due to maternal autoantibody transfer 3, 4
Excluding Other Diagnoses
Bernard-Soulier syndrome and neonatal alloimmune thrombocytopenia are excluded because:
- Both would present with thrombocytopenia, not a normal platelet count 2
- Both would have normal aPTT, as they are platelet disorders not affecting the intrinsic coagulation pathway 2
Confirmatory Testing Required
To definitively establish the diagnosis, the following should be performed immediately:
- Factor VIII activity level measurement - will be reduced in acquired hemophilia A 1
- Bethesda assay to quantify the factor VIII inhibitor titer, though it may underestimate autoantibody potency due to type 2 kinetics 1
- Factor VIII antibody ELISA if results are ambiguous or to distinguish from lupus anticoagulant 1
- Lupus anticoagulant testing to exclude this alternative cause of non-correcting mixing studies 1
Critical Management Considerations
Given the high mortality risk (9-31% in historical series) associated with acquired hemophilia A 1:
- Immediate hemostatic control is the priority using bypassing agents (recombinant activated factor VII or activated prothrombin complex concentrate) 1
- Immunosuppressive therapy should be initiated immediately upon diagnosis to eradicate autoantibodies 1
- In neonates with maternally-derived antibodies, the condition may be transient as maternal antibodies clear 6
The combination of failed mixing study correction with spontaneous bleeding in a neonate strongly indicates maternal autoantibodies causing acquired hemophilia A rather than congenital factor VIII deficiency 3, 4, 5.