What is a mixing study, how is it performed and what is it purpose?    (20% marks)

[Click here to toggle visibility of the answers]

College answer

Mixing studies distinguish between factor deficiencies and the presence of inhibitors. They are performed by measuring the clotting time of the patient’s plasma diluted serially with normally plasma. If the mixture yields a 10% near normal results the study is said to be corrected and factor deficiency is inferred.

Discussion

The weird design of the second paper of 2019 put his SAQ (directly asking about mixing studies) together with a bunch of questions (Question 5.2 and Question 5.3) which, for their correct interpretation, required the trainees to be able to interpret mixing studies. Ergo, if the trainee knew nothing at all, they would have scored poorly in all three SAQs. It is difficult to guess what additional advantage was obtained by this direct question, as compared to another question testing the trainees' understanding of mixing studies by means a clinical scenario. Some might say the latter is positioned higher in Bloom's taxonomy pyramid. 

Anyway.  Lets say your sample of plasma is giving a high PT or aPTT - grab your suspicious plasma sample, and mix it with normal blood plasma, 50:50. Obviously, if some sort of "factor inhibitor" is present, the normal blood will also be affected, and the resulting mixture will give abnormal aPTT and PT results. However, if there is a factor deficiency, the mixed sample will result in a normal PT or aPTT because the missing factors were contributed in the normal sample.

In short exam-focused point form:

  • Patient plasma is mixed 1:1 with normal plasma
  • APTT and PT are measured immediately
  • Complete (with 10%) correction of PT /APTT suggests a factor deficiency
  • Plasma is incubated for 1 hour at 37°C
  • The mixing studies are repeated 
  • A longer APTT after 1 hour incubation suggests a factor VIII inhibitor.

References

References

Miller, C.H. "Mixing Studies". Ch 130. in: Transfusion Medicine and Hemostasis (Third Edition), 2019, Pages 783-784