From Vanessa Chan, Sick Kids Hospital, Toronto:
Hi George, What is your opinion on the algorithm of tests when testing for lupus anticoagulant? If the mixing tests are normal, should we continue with a confirmatory test? The recent BJH guidelines say, “Mixing tests are a criterion for LA and improve the specificity. However, they introduce a dilution factor and may make weak LA samples appear negative. In the absence of any other causes of prolonged clotting times, such samples should be considered LA positive if the screen and confirmatory tests on undiluted plasma give positive results. Whenever possible, this should be confirmed by testing a fresh sample.” This indicates that a confirmatory test is done even when mixing studies correct (appear negative). Responses from other labs and clinicians are most welcome!
Hi, Vanessa, and thank you for your question. When a patient specimen has a prolonged partial thromboplastin time (PTT) and you have ruled out heparin, you first mix 1 part patient platelet-free-plasma with 1 part platelet-free pooled normal plasma (PNP) and performing an immediate PTT on the mix. If the result “corrects” to within 10% of the PNP PTT, incubate 1–2 hours at 37°C and repeat, comparing the result to the result of incubated PNP. Some LAs are time- and temperature-dependent, so you may detect an LA upon incubation.
If the immediate and incubated mixing study results both correct, but there is high suspicion of LA, some lab operators repeat both immediate and incubated PTT mixes using 4 parts patient plasma to 1 part PNP, which provides greater sensitivity for the LA. If the 4:1 mix corrects in both phases, LA may be ruled out and it is not necessary to continue with the LA screen and confirm test. In all cases, ensure the patient specimen and the reagent PNP are platelet-free.
I hope this helps, and I invite comments, as labs all tend to approach this question in different ways.