Mixing Studies and the Rosner Index

Here is a 2-12-2024 message from Brenda Goforth, Senior CLS Hematology, Coagulation, and Urinalysis; Clinical Laboratory Antelope Valley Medical Center, Lancaster, CA 93534.

Hello, I would like some clarification on the subject mixing studies using the Rosner Index cutoff compared to the “>10% of the normal pooled plasma [NPP] limit” in regards to incubation of the NPP at 37 C. When using the Rosner Index do the patient specimen and and NPP need to be incubated separately and then mixed and tested along with the 1:1 patient/NPP? Would this be the NPP portion of the equation? Or does the NPP need to be incubated and then run without the patient part of the incubation? I have a book, An Algorithmic Approach to Hemostasis Testing, that refers to the incubation of the NPP and patient separately and them mixed and tested along with the 1:1 mix. For the >10% approach am I understanding it correctly that the NPP needs to be incubated only without the patient?

From George: Hello, Brenda, and thank you for your email. The short answer is no, you need not incubate the NPP and patient specimens separately when using the Rosner index or when using the >10% of the NPP PTT as the cutoff. I confirmed this with Dr. Ali Sadeghi-Khomami, Precision BioLogic Inc. researcher, who mentioned that the cutoff for the Rosner index is a ratio of 0.15, meaning <0.15 indicates correction, and >0.15 is no correction. It is necessary to set your own cutoff, for instance, our facility uses 0.11. I’ve attached a copy of a mixing study presentation slide deck from 2016 which references the Rosner and the Chang index. The Chang index does require incubation of the NPP, patient specimen, and mix. The presentation also references the 10% cutoff based on the NPP PTT result and facilities that use the upper limit of the reference interval. I advocate for using the NPP value as the decision basis rather than a fixed value.

See also Dr. Sadeghi-Khomami’s comment appended to our 1-31-2024 discussion, “Interpreting Inhibitor Mixing Study in a Hemophilia A Patient.”