Why might mixing studies fail to correct an isolated prolonged aPTT?

• A. Presence of an inhibitor such as lupus anticoagulant or a specific factor inhibitor.
• B. Platelet aggregation defect.
• C. Factor II deficiency.
• D. Vitamin K deficiency.

Answer: (A)

Mixing studies test whether a prolonged aPTT is due to a deficiency of intrinsic pathway factors or to an inhibitor. When normal plasma is mixed with patient plasma, a deficiency is corrected because the normal plasma supplies the missing factors, restoring the pathway and normalizing the clotting time.

If an inhibitor is present, the inhibitor remains active in the mixture and continues to interfere with the assay. Lupus anticoagulant, a common inhibitor, targets phospholipid-dependent steps of the coagulation cascade, so adding normal plasma doesn’t overcome the inhibition and the aPTT stays prolonged. A specific factor inhibitor similarly neutralizes the affected factor even after mixing, preventing correction.

In contrast, a deficiency of factors like factor II would be corrected by the added normal plasma, and vitamin K deficiency–related factor depletion would also be replenished by the normal plasma, leading to normalization of the aPTT.

So, the reason mixing studies fail to correct an isolated prolonged aPTT is the presence of an inhibitor that remains active in the mixture.