In patients with a factor VIII inhibitor, how does the APTT behave after mixing studies?

In patients with a factor VIII inhibitor, mixing studies play a crucial role in understanding the behavior of activated partial thromboplastin time (APTT). When a sample from a patient who has a factor VIII inhibitor is mixed with normal plasma, the expectation is that some aspects of coagulation function might be restored. However, due to the presence of the inhibitor, the APTT initially shows a prolonged result.

The delay in correction is because the inhibitor binds to the factor VIII in the normal plasma, rendering it inactive. Thus, after mixing, there is a temporary semblance of correction, but as the sample is incubated, it continues to express its prolonged APTT. This is a classic behavior seen with factor inhibitors where, upon incubation, the inhibitor continues to act on the added factor VIII from the normal plasma, leading to a further prolongation of the APTT. This distinctive pattern—initial prolongation that worsens with incubation—is a hallmark of factor VIII inhibitors and is why this answer is correct.

This phenomenon is clinically significant as it directs the diagnosis towards specific treatments and management of patients with hemophilia A complicated by inhibitors. Understanding this helps clinicians provide appropriate therapeutic measures to manage bleeding risks in these patients effectively.