From Dr. Ning Tang:
Hi, George, We have a patient with strong lupus anticoagulant (LAC or LA). Diluting the plasma can’t recover the intrinsic factor activities (all <20%), also all results of the intrinsic factor inhibitors were positive. Hence we replaced the APTT reagent by a silica clotting time reagent that contains sufficient phospholipid and is used as confirmatory test for LA, and built new factor and factor inhibitors calibration curves. From them we got normal intrinsic factors activities and negative inhibitors results for the patient plasma. Do you think this method is credible? Thank you!
Hello, Dr. Tang, and thank you for your question, which I discussed with my colleague and coagulation expert, Dave McGlasson, MLS. We agree that your approach is acceptable, provided you have adequately validated the confirmatory reagent and method. According to Pengo V, Tripodi A, Reber G, et al, Update of the guidelines for lupus anticoagulant detection. J Thromb Hemost 2009; 7: 1737–40, the PTT reagent that is most sensitive to LA provides silica as its activator and has a low phospholipid content. Pengo and colleagues suggest that ellagic acid activator is not sufficently sensitive to LA and should not be employed for LA detection. Having established the presence of LA, if there is reason to measure procoagulant levels, a PTT reagent with intermediate or low LA sensitivity is necessary, and if the initial PTT result using this reagent is prolonged, the specimen should be diluted to the point where the LA effect is lost so that the operator may estimate the procoagulant levels. I hope this is helpful.
Years ago I used a reagent
From Dave McGlasson: Years ago I used a reagent called Actin FSL which had an ellagic acid activator for APTT testing for the presence of a LA with great success. However, when doing comparative studies with different reagent combinations the silica activated reagents did perform better.
Dave, I’m not certain why the ISTH committee rules against ellagic acid-based PTT reagents for LA detection, do you know?
Thank you for the comments,
Thank you for the comments, the activator of the STAGO APTT reagent we used is silica, in fact most of the certificated APTT reagents in China are silica reagents now, we have few chances to realize the difference between silica and ellagic acid.
Hi George and Ning,
Hi George and Ning,
I would both agree and disagree with some of these comments. First, if you have used an APTT reagent with sufficiently high phospholipid to neutralise the LA activity and you have obtained normal factor levels and no factor inhibitor detection with this reagent, as compared to a previous reagent with ‘less phospholipid,’ then this would seem to evidence an LA effect. However, Ning did not mention which specific reagents were used, and this may be important. In regards to differential sensitivity of ‘ellagic acid’ vs ‘silica’, I think there is insufficient conclusive evidence, and this distinction may be over simplistic. Again, I would refer to a paper from a colleague, who showed that ellagic acid reagents could also be sensitive to LA: Kershaw G, Suresh S, Orellana D, Nguy YM. Laboratory identification of lupus anticoagulants. Semin Thromb Hemost. 2012;38:375–84. Although current commercial silica based reagents are generally more LA sensitive than ellagic acid reagents, I suspect this is not always going to be the case in the future.