Diagnosis: Maternal Autoantibodies Leading to Acquired Hemophilia (Option D)
The most likely diagnosis is maternal autoantibodies causing acquired hemophilia A (Option D), as the failure of aPTT to correct on mixing study indicates the presence of an inhibitor rather than a simple factor deficiency.
Diagnostic Reasoning Based on Laboratory Pattern
The key diagnostic feature is the non-correcting mixing study, which distinguishes between factor deficiency and inhibitor presence:
- Immediate correction of aPTT with normal plasma indicates factor deficiency, while failure to correct suggests an inhibitor (lupus anticoagulant or factor inhibitor) 1
- A Rosner index ≥11% indicates inhibitor presence rather than factor deficiency 1
- In this neonate, the mixing study failed to correct, definitively pointing toward an acquired inhibitor rather than congenital hemophilia A 1
Why Not Factor VIII Deficiency (Hemophilia A)?
Congenital hemophilia A (Option A) is excluded because:
- In true factor VIII deficiency, the mixing study would show immediate correction when patient plasma is mixed with normal plasma 1, 2
- Hemophilia A is X-linked and would not present with maternal antibody transfer 3
- The clinical presentation with spontaneous bleeding and hemarthrosis fits hemophilia, but the laboratory pattern does not 3
Why Not Platelet Disorders?
Bernard-Soulier syndrome (Option B) and neonatal alloimmune thrombocytopenia (Option C) are excluded because:
- Both conditions present with thrombocytopenia, not a normal platelet count 3, 4
- Bernard-Soulier syndrome affects platelet function and would not prolong aPTT 5
- Neonatal alloimmune thrombocytopenia requires maternal antibodies against platelet antigens (HPA antigens), causing low platelet counts, not coagulation factor inhibition 3, 4
- The normal platelet count in this case definitively excludes both platelet disorders 3, 5
Acquired Hemophilia A in Neonates
Maternal autoantibodies against factor VIII can cross the placenta and cause transient acquired hemophilia in neonates:
- Acquired hemophilia A occurs due to autoantibodies against factor VIII that neutralize its procoagulant function 2, 6
- The diagnosis is based on isolated prolongation of aPTT that does not normalize after addition of normal plasma, along with reduced factor VIII levels 2, 7
- Hemarthrosis, while the hallmark of congenital severe hemophilia A, seldom occurs in acquired hemophilia A, making this presentation somewhat atypical but still consistent with severe antibody-mediated factor VIII inhibition 2
- Postpartum women are at highest risk for acquired hemophilia A, and maternal antibodies can transfer to the neonate 1, 8
Clinical Presentation Correlation
The spontaneous soft tissue bleeding and joint swelling indicate:
- Severe coagulation impairment consistent with factor VIII inhibition 2, 6
- The severity of bleeding correlates with the degree of factor VIII neutralization by autoantibodies 3
- Unlike congenital hemophilia where hemarthrosis is common, the presence of hemarthrosis in acquired hemophilia suggests particularly severe antibody-mediated inhibition 2
Critical Diagnostic Pitfall to Avoid
Do not assume that failure to correct on mixing study always means lupus anticoagulant - in the context of clinical bleeding (especially spontaneous bleeding and hemarthrosis), this pattern strongly suggests factor VIII inhibitor and requires immediate Bethesda assay to quantify inhibitor titer 1, 8, 7