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PTT Prolongation Limit and Mixing Studies

I received the following question from Dr. Robert Gay at Greensboro Pathology Associates, Greensboro, NC:

It makes sense not to perform a mixing study when the partial thromboplastin time (PTT) is just above the reference range but what is commonly used as a cutoff? Is there a way that individual labs can establish what their limit should be?

Hello, Dr. Gay, and thank you for your question. This actually was posted as a Quick Question back in July, summarized in Quick Question: Mixing Studies on August 15, 2010. It came up again in an October 11, 2011 discussion of prothrombin time (PT) and PTT reference intervals. It seems there is no firm answer, although 43% of the responders simply chose “Any non-heparin PTT that is prolonged beyond the upper limit of normal.” It is helpful to realize that 28% also responded they solicit clinical information before performing mixing studies. I think this is an fertile question for a good clinical laboratory researcher.

Comments (1)
Feb 2, 2011 7:01am

Hi George and Dr. Gay. The sheer volume of discussions conc
Hi George and Dr. Gay. The sheer volume of discussions concerning PTT mixing studies in this forum indicates the need for a comprehensive evaluation of the topic. One would like for a quick, clear and concise answer so that we can say “yes, we have a problem,” or “no, we definitely do not have a problem.” I am sure there is no easy answer.

To address Dr. Gay’s question one must determine what is being looked for in the mixing study and how are we going to look for that answer. The first question being, are we looking for a factor deficiency? Here is where mixing studies can definitely be of value for the pathologist and clinician, and we can generally answer with a resounding “normal” or “not normal.”

The second question to ask “is an inhibitor present in our patient?” The PTT mixing study will usually be very informative if a factor inhibitor is present.

The third question to ask “is a lupus anticoagulant (LA) present in our patient. The original post from Dr. Gay indicates the patient’s PTT was slightly above the normal range. A mixing study is of limited utility in LA workups. In our experience, LAs do not necessarily prolong the PTT and mixing studies do not always show abnormal results.

The best answer for this question is three fold. The first is to resist the desire to discuss the need for mixing studies in absolute terms. While we would love to establish criteria as to when and when not to perform mixing studies, that is just not the case. The second point is to understand the needs of the clinician and patient. Are we looking for factor deficiency, factor inhibitors or LA? And lastly, we need to understand our test systems and methodology and identify its sensitivities, strengths and weaknesses.

Herb Crown
St. Louis University Hospital Coagulation Reference Laboratory

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