From Kim Kinney. (Clarian gets the most interesting cases.)

Hi George.
We have a patient with an acquired factor VIII (FVIII) inhibitor.  He started out having <1% VIII, but he is now up to 33%.  He has had a Bethesda titer all along, but it is starting to go down.  One thing I noticed is that when his VIII level got above around 30% we started having issues with his Bethesda titer in that the lower dilutions did not make much sense.  We had a 1:2 dilution with residual FVIII of 50% but then it went down with more dilutions until we hit the 1:16 dilution and it was back up to 51%.  From there, the FVIII went up in order.  I know that acquired antibodies follow second order kinetics and are not always accurate.  What is the VIII level above which you really should not do a Bethesda titer?  I would like to be able to tell docs above  certain VIII we do not do titers. Thanks for the help.

Hi George,
I am a MLT and I am currently working on my MT. I have a few questions about mixing studies. I have listened to several of your modules on your website but I am still having trouble with understanding factor deficiencies in certain scenarios. If a patient has a prolonged PT and PTT that corrects with normal pooled plasma but has an abnormal Russell Viper venom test and all other screening tests are normal, what factor deficiency could this patient have? I think it might be factor X deficiency but I am not exactly sure.

Another question I have is the same scenario as above, the prolonged PT, PTT is corrected by pooled plasma, all other screening tests are normal including the Russell Viper venom test. Does this sound like a factor deficiency such as V, II  X or a vitamin K deficiency?

Thank You for reading and any help understanding this would be greatly appreciated.
Vanessa

Jane Bossart originally posted this question on MEDLAB. I'm posting it here with her permission:

Hello,  I have a few questions about mixing studies. What do your labs use for "normal plasma (PNP)"?  If you purchase it, have you had any problems with it? What are your criteria for correction for both PT and APTT?

Thanks

Jane Bossart
Tri City Medical Center
Oceanside Ca

Here is another interesting question about mixing studies from blog participant Sue Hollister:

Over the past year we have had a few aPTT mixing studies where the initial 1:1 mix was actually longer than the orginal  prolonged aPTT.  For example, the original prolonged aPTT was 40 seconds, the initial 1:1 mix was 43 seconds and after 1 hour incubation the mix was 45 seconds. We are using a commercial normal pooled plasma to perform our mixes and this has happened with both fresh and frozen samples.  We have ruled out heparin and other anticoagulants as well.  Do you think it has something to do with the draw itself?
 
Thank you, Sue Hollister

From Lester Jones at Triad:

I am trying to find out what is the most effective mixing study ratio for lupus anticoagulants. Currently we are using a 1:1 mix for the DRVVT test. I think that a 1:4 would be better.  What do you recommend?

George,  I have just discovered your website while I was searching for articles on mixing studies.  I am looking for an actual procedure on performing the mixing studies.  Would you be able to refer me to a source for this? 

Thanks, Louise Schafer (Louise does not give her location)

George: I was looking at different coagulation methods, possibly doing factor testing and mixing studies.  We are looking at various instruments, one being the ACL TOP.  I was wondering if there was a list of the specific disease states and the correction factors involved.  For example, if a specimen was corrected by the addition of normal pooled plasma, but the Russell viper venom test was abnormal, what disease state would this indicate?  It would be nice to have a chart for quick reference.  Thanks for your time.

Julie Schartiger MLT (ASCP)
Holzer Medical Center
100 Jackson Pike
Gallipolis, OH  45631

As you saw from my recent "Coagulation Factor Inheritance" post, I had the opportunity to assist with the University of Medicine and Dentistry of New Jersey, www.umdnj.edu, graduate hemostasis course. In addition to working with course coordinator, Elaine Keohane, PhD, I had the privilege of collaborating with my friend and colleague, Larry Smith, PhD. Larry contributed chapter 7, Hematopoietic Theory, to the third (2007) edition of Rodak BF, Fritsma GA, Doig K. Hematology Clinical Principles and Applications and is the Director of the Coagulation and Hemostasis Laboratories at Memorial Sloan-Kettering Cancer Center in New York City. In the course of discussions, Larry mentioned the silica clotting time (SCT), which I had not heard of, and I asked him to prepare a guest blog on the subject. His description of the SCT will appear tomorrow, Thursday, May 15. Geo.

I have a question about the post regarding mixing studies and CAP checklist question 37991. (I have been trying to post this on “The Fritsma Factor” with no success.)

I thought CAP question 37991 addressed appropriate plasma for mixing studies. If this is the case, is it appropriate to use lyophilized plasma for mixing? I thought that practice was discouraged.

If the post is referring to controls for mixing studies, do you think that is required?  I remember a CAP posting from years ago (John Brandt) that said since the testing is really PT or APTT based, your usual PT/APTT controls should suffice; you would not need to run specific controls for the mixing studies.

Thank you for clarification (and “The Fritsma Factor”)
 
Nancy Fabbrini

George: We recently had a CAP inspection and had a couple of recommendations that we're trying to tidy up.

1.  HEM 37991 regarding a control for PT mixing studies. We were using what we considered to be the normal control but were told to order the Dade Control N. I've ordered and just want to make sure that the control contains normal levels of each factor. I'm hoping the package insert will provide me with the documentation but just off the top of your head, is it an acceptable control?

2.  HEM 38002 regarding documentation showing the procedure either includes a process to detect heparin or other antithrombotic drugs OR does the patient report include a comment that the effect of inhibitor drugs cannot be excluded. Can you share a mixing study procedure that would include that verbiage?  We don't include a process to detect heparin as we just do a quick mix patient with control and see if corrects.   Anything more complicated gets sent out. Thanks, George.

Joanne Kendrick, MT(ASCP)
Core Lab Supervisor
LabCorp at Brookwood Medical Center
Birmingham, AL