From Aliaa Amer: Hi George, we are using Actin FSL for our routine activated partial thromboplastin time (APTT, PTT). Whenever we get a prolonged APTT that is >5 s above the upper limit of the norm range we do mixing studies, both immediate and 2 h incubation using 1:1 and 4:1 mix, the latter to detect weak lupus anticoagulant (LA). In many instances we get full correction and we proceed to factor assays which turn out to be normal. Then we test for LA using the dilute Russell viper venom time (DRVVT). To our surprise we find it is positive for a mild LA (LAS/LAC = 1.5, our cut off is 1.2) which could not be detected even by the 4:1 preparation. Do you have any explanation for this? We are using the Siemens BCS analyzer.
Hello, Aliaa Amer, and thank you for your question. Siemens Actin FSL possesses low affinity for lupus anticoagulant (LA), as described in Fritsma GA, Dembitzer FR, Randhawa A, et al. Recommendations for appropriate activated partial thromboplastin time reagent selection and utilization. AM J Clin Pathol 2012;137:904–8, please pardon the self-reference. Mild prolongation may reflect a lupus anticoagulant effect, however it is more likely caused by a factor deficiency. One factor we don’t usually assay routinely is factor XII, this could be the culprit, as mild factor XII deficiency is not uncommon.
Assuming that you use the same Actin FSL in your mixing study, it may be insensitive to a weak LA, even in the 4:1 ratio, yet you can demonstrate the LA in the more sensitive DRVVT system. Further, owing to LA heterogeneity, PTT-based lupus anticoagulant detection and confirmation systems need not agree with DRVVT-based systems. A positive confirmatory test result in either one or the other is conclusive for LA, provided you’ve ruled out other potential causes for the originally prolonged PTT.
By the way, you don’t mention it, but I assume the specimens that produce these results are anticoagulant-free. Also, I’m curious as to how many times you’ve seen this. I had a brief conversation with Dr. Thomas Ortel at the ASCLS/AACC meeting this summer in Houston, and he recommends that when there is clinical or laboratory suspicion of LA, that you continue with the screen and confirmatory studies even when the mixing study corrects.