In a patient with a prolonged aPTT that does not correct after a 1:1 mixing study, which diagnosis is most likely?

• A. Factor deficiency
• B. Factor VIII inhibitor
• C. Vitamin K deficiency
• D. Factor XII deficiency

Answer: (B)

Mixing studies are used to tell apart a simple deficiency from an inhibitor in a prolonged aPTT. If adding normal plasma corrects the abnormal clotting time, the problem is a lacking factor. If the aPTT remains prolonged despite mixing, an inhibitor is present that neutralizes the factors in the mix. The most classic inhibitor in this scenario is an antibody against factor VIII, which blocks activity even when normal plasma supplies factor VIII. That’s why the prolonged aPTT does not correct with a 1:1 mix.

Vitamin K deficiency would involve multiple vitamin K–dependent factors and would more likely show partial correction with mixing, not a persistent noncorrection. Factor XII deficiency prolongs aPTT but does not cause bleeding and would typically correct with mixing because there’s no inhibitory antibody involved. A factor VIII inhibitor fits the pattern and is the best explanation for a non-correcting prolongation after mixing.