Here is a message from Ms. Khaldee Lindsey Davenport-Landry (Lindsey), a graduate student in this spring’s University of Medicine and Dentistry of New Jersey’s graduate course, CLSC 5124, Advanced Hemostasis. Lindsey is an experienced medical laboratory scientist; she asks about mixing studies:
We do a rare mixing study at our hospital, and even more rare PTT mixing study. We have in our procedure that if the correction of the PTT is within reference range, we should then do the incubated PTT mix. I do not remember talking about this in the recent coag class you helped to teach.Just wondering if this procedure needs a face lift.
Hello, Lindsey, and thank you for the question. Your procedure is correct, if the PTT is prolonged and the prolongation is corrected in a 1:1 mix, the next step is to incubate the mix for two hours at 37ºC and repeat. Your purpose is to detect any potential time- and temperature-dependent inhibitor. The specific inhibitors, in particular anti-factor VIII are usually IgG4, which is often detected only upon incubation. The procedure for mixing studies is provided in our Audio Module 25, which also discusses our various definitions for correction.
Though textbooks assert that the non-specific inhibitor, lupus anticoagulant (LA), is not time- and temperature-dependent, there are some LAs that in fact do require at least brief incubation. To create more confusion, some specific anti-FVIII antibodies may be detected in the immediate 1:1 mix. For this reason, some laboratory directors simply skip the immediate mix and do all mixes after a 1- or 2-hour incubation.
If this is true, how do you differentiate? The clinical picture gives the answer: someone with LA may have experienced a thrombotic event or may be asymptomatic. Someone with anti-FVIII is nearly certain to be bleeding, often hemorrhaging.
The UMDNJ will offer their graduate Hemostasis course again in spring of 2014, and next year will offer its graduate Hematology course.