A 35-year-old male presents with sudden severe hemorrhagic problems. Platelet count is normal, PFA-100 is normal, PT is normal, aPTT is markedly prolonged and does not correct after a 1:1 mixing study. These findings are most consistent with which diagnosis?

• A. Lupus anticoagulant
• B. von Willebrand disease
• C. Hemophilia A
• D. Factor VIII inhibitor

Answer: (D)

When the aPTT is markedly prolonged and does not correct after a 1:1 mixing study with normal plasma, the pattern points to an inhibitor against a clotting factor rather than a simple deficiency. Here, the findings fit an acquired antibody against factor VIII. That autoantibody neutralizes factor VIII in both the patient’s plasma and the added normal plasma, so the intrinsic pathway remains impaired and the aPTT stays prolonged.

The normal platelet count and a normal PFA-100 indicate platelet function is intact, and the normal PT shows the extrinsic pathway is unaffected, focusing the problem on the intrinsic pathway where factor VIII operates. Among possibilities, a lupus anticoagulant can also prolong the aPTT and resist mixing, but it typically associates with thrombosis rather than severe bleeding, making an anti–factor VIII inhibitor a more consistent explanation for this bleeding presentation. Von Willebrand disease would usually affect platelet adhesion and often alter PFA-100 results, and a congenital factor VIII deficiency would typically correct with mixing, not persist as prolonged.

So, the most consistent diagnosis is an acquired factor VIII inhibitor (acquired hemophilia A).