An aPTT That Will Not Sit Still

An adult specimen comes back with PT 11.8 s (interval 10.5-13.5 s), normal, and aPTT 68.4 s (interval 25.0-35.0 s), markedly prolonged. Medication reconciliation at the time of collection shows no reported heparin, direct oral anticoagulant (DOAC), emicizumab, or recent factor VIII (FVIII) concentrate, so an obvious drug explanation is not sitting in front of you. The specimen is citrated platelet-poor plasma with no visible hemolysis or clot, collected before any transfusion.

A 1:1 mix with normal pooled plasma is run immediately and again after roughly two hours of incubation at 37 C. The immediate mix aPTT comes back at 39.1 s, a partial correction toward normal. The 2-hour incubated mix comes back worse, at 61.7 s, close to the original prolonged result. That pattern alone does not answer the question at hand. It tells you where to look next, not what the answer is.

The question for this case: which factor assays or inhibitor studies can confirm whether this pattern reflects a missing factor or a factor being actively neutralized, and where could assay interference send you the wrong way? Answering that requires knowing what a factor assay actually measures, how a chromogenic method differs from a one-stage clot-based method, and what a Bethesda titer can and cannot tell you.

A partial-correction, worsening-on-incubation mixing pattern is a reason to plan a targeted factor and inhibitor workup, not a diagnosis by itself.