LAC Profile: PTT Versus PTT-LA

From “Ari.” Hi George, I stumbled upon your amazing site when researching this question and was wondering if you could shed some light on this. I have a patient who had a DVT. His PCP noted a slightly prolonged aPTT and sent mixing studies. From what I can tell, the aPTT mostly corrected with mix, but the PTT–LA is definitely long and only slightly corrects (basically it stays prolonged). I understand the PTT–LA results as indicative of a lupus anticoagulant (LAC) which fits the clinical picture of DVT, but I’m having trouble understanding why the aPTT would correct on mixing. Can you shed some light on this?
I’ve copied the relevant labs with patient identifying factors removed to this link: https://imgur.com/a/e0ubV. (Readers go to the link for the patient data, Geo.)

Hello, Dr. “Ari” and thank you for your compliment. I reviewed your data with Oksana Volod, MD, a colleague and friend. She is Director, Coagulation Consultation Services, Cedars Sinai, Los Angeles. Dr. Volod responds…

• The PTT prolongation is too small to warrant a mixing study, thus the correction data can’t be reliably interpreted. [Added by Geo: Many lab scientists and pathologists recommend setting a minimum prolongation of, for instance, 5 seconds above the upper limit of the reference interval as a mixing study trigger.] In this instance, assuming LAC is present, the PTT reagent is perhaps insensitive to LAC, or, equally likely, the LAC possess low avidity. Dr. Volod recommends bypassing the mix and going straight to the LAC profile, based on clinical presentation.
• Dr. Volod also mentions she finds little utility for the saline mix, though many “seasoned” lab scientists like how it can help indicate a factor deficiency. She also prefers a two-hour incubation, and does not perform an additional normal plasma mixing study as part of the LAC profile.. [From Geo: Though not a strict guideline, the CDC recommends two-hour mixing study incubation on the principle that we do two-hour Nijmegen Bethesda Assay incubations when measuring factor inhibitors. Also, the ISTH guidelines recommend eliminating the normal plasma mixing study as part of the LAC profile, though many find it to be helpful in making their interpretation.]
• Dr. Volod concludes, clearly LAC is positive, be sure to repeat the work up in 12 weeks.

In addition, another “clotter” friend, colleague, and co-author, Dave McGlasson responds, “This is one of those times when Doug Triplett’s 4:1 mixing study might be warranted to increase sensitivity in detecting LACs.” He refers to the recommendation of the late Douglas Triplett, MD, of Muncie, who recommended a 4:1 ratio of patient plasma to normal plasma as a means for detecting LACs whose avidity is low but which may still have clinical consequences.

A final comment, this case illustrates how various PTT reagent formulations may be more or less sensitive to LAC. If you will pardon my self-reference, see Fritsma GA, Dembitzer FR, Randhawa A, Marques MB, Van Cott EM, Adcock-Funk D, Peerschke EI. Recommendations for appropriate activated partial thromboplastin time reagent selection and utilization. Am J Clin Pathol. 2012;137:904–8