Mixing Studies

The first step in determining whether there are one or more deficiencies in blood coagulation proteins that might account for a bleeding tendency is to perform the basic screening tests of blood coagulation, namely the Prothrombin Time (PT) and the Activated Partial Thromboplastin Time (APTT). If one or both of these tests is abnormal, the next step is to establish whether the abnormality is due to a coagulation factor deficiency, or an inhibitor of the coagulation process. The test that permits this distinction is known as the Mixing Study.

In this test, the patient's plasma is mixed with an equal volume of normal plasma (which contains normal levels of all the clotting factors). The PT and/or APTT (depending on which one originally showed an abnormality) is then repeated on the mixture and the result(s) compared to that of the normal and patient's plasma alone. The tests on the mixture are performed both immediately after the mixing and after 2 hours of incubation at 37oC. The latter step allows the detection of FVIII inhibitors that are typically time- and temperature-dependent.

 If the abnormal clotting time is corrected by addition of normal plasma, we can deduce that the problem was caused by a clotting factor deficiency. If however, the abnormality persists in the mixture of normal and patient plasma, or was incompletely corrected, then we can suspect the presence of a coagulation factor inhibitor (including a Lupus Anticoagulant).