A patient with acquired hemophilia A has a prolonged aPTT that does NOT correct with a 1:1 mix of patient plasma with normal plasma. What does failure to correct in the mixing study indicate?

• A A factor deficiency — missing clotting factors are present in the normal plasma and would correct the aPTT
• B The presence of an inhibitor (e.g., anti-Factor VIII antibody) in the patient's plasma that inactivates Factor VIII in the normal plasma as well ✓
• C The patient has von Willebrand disease — vWF is not donated by the normal plasma in a 1:1 mix
• D Lupus anticoagulant — the mixing study corrects because phospholipid is provided by normal plasma

Explanation

In a 1:1 mixing study, normal plasma provides all clotting factors in sufficient amounts to correct deficiencies — a prolonged aPTT that corrects suggests a factor deficiency. If the aPTT does NOT correct after mixing, an inhibitor is present in the patient's plasma that neutralizes the clotting factor in the normal plasma as well. In acquired hemophilia A, auto-antibodies (usually IgG4) against Factor VIII neutralize FVIII activity; the anti-FVIII antibody in the patient's plasma also destroys the FVIII contributed by normal plasma. Lupus anticoagulant is also inhibitor-type but in vivo is prothrombotic, not hemorrhagic.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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