Inhibitor Screen

The PT and APTT may be prolonged due to the deficiency of one (or more) clotting factors or to the presence of an inhibitor that interferes either specifically or non-specifically with coagulation factors. An inhibitor screen (mixing study) can help to distinguish between these possibilities.

These tests are performed by mixing the patient's plasma with an equal volume of normal pooled plasma. The test that was originally prolonged (PT and/or APTT) is then repeated on the mixture. For the APTT, correction is indicated by a clotting time of the normal/patient plasma mix that is within 5 seconds of the normal plasma alone. If the clot time does not correct to within 5 seconds of the control plasma, an immediate-acting inhibitor is present. Because only 30-40% of any given clotting factor is necessary to give normal results in the PT and APTT, correction of the clot time of the immediate mix indicates deficiency of one or more clotting factors.

In the investigation of a prolonged APTT, the mixing study also includes an incubated mix in which the normal/patient mix is incubated for at least 60 minutes at 37 degrees Celsius. As an additional control to correct for labile clotting factor loss during incubation, the normal plasma alone is incubated in parallel. Detection of an inhibitor in the incubated mix, but not in the immediate mix, indicates the presence of a progressive-type inhibitor, usually directed against FVIII. The Hemostasis and Thrombosis Laboratory recommends that the finding of a progressive inhibitor of the APTT be followed up with specific assay of FVIII and FVIII inhibitor (Bethesda titer).

The Hemostasis and Thrombosis Laboratory does not provide a normal range for inhibitor studies. Instead, each test carries a specific interpretation, such as "No inhibitor Detected", "Immediate-Acting Inhibitor Present" or "Progressive Inhibitor Present" with suggestions for further evaluation.