George has had several conversations with frequent contributor and international expertDave McGlasson (Wilford Hall USAF Medical Center, San Antonio) about normalizing the DRVVT ratio on the laboratory’s DRVVT mean of the reference interval in accordance withZhang L, et al: A simplified algorithm for the laboratory detection of lupus anticoagulants. Am J Clin Pathol 2005;124:894–901. The author states, “The normalized ratio is recommended to correct for differences in instrument-reagent combinations and to improve discrimination between normal and low-positive LA samples. The formula for normalization is attached in this link: DRVVT Normalization Ratio.
In an email conversation with Dave, frequent contributor Dr. Emmanuel Favaloro(Australia) wrote: “We have always used normalised ratios. It doesn’t make sense to me not to, since the baseline values for the screen and confirm are invariably different. Moreover, they will change slightly with different batches of reagents and different normal pools. On the other hand, if you have established your normal ranges based on non-normalised data you might be OK.”
The purpose for this post is to ask you, do you know about normalization of the DRVVT ratio, do you use it, do you advocate for it, and what advantages does the ratio provide?
Hi George, Fritsma Factor contributors and readers,
We a
Hi George, Fritsma Factor contributors and readers,
We are aware of the DRVVT normalization ratio and the recommendations to use it, however, we are currently not using it. There are a couple of reasons. When we validated our cut-offs, we used about 40-50 normals and calculated them using the 99th percentile (not 2SD and not 3SD). When we switch lot numbers of PPP, lupus sensitive PTT and DRVVT reagents, we have found that the QC ranges do not shift very much (we use our PPP as a normal QC as well) and so we have always kept the same cut-offs to date. I guess this is where Dr. Favaloro would say we may be OK since we validated our normals using non-normalized data and our ranges have not changed much.
We took a look retrospectively at 200 samples and calculated a normalized ratio for each step of our testing: Lupus sensitive PTT, DRVVT screen and if applicable, DRVVT screen and confirm ratio. The normalized ratio cut-offs were calculated based on our initial validation samples. We found only 1 sample where using the ratio, we would have continued on with a confirmatory step. On the other hand, there were a lot of samples where the mixing corrected and we did not continue with confirmation testing.
The value of the normalized ratio would be that it does correct for slight differences in PPP and reagent lots but at the same time, it also adds an extra calculation or two or three which increases the chance of error and adds to workload.
On a different note: after I posted the question about mixing studies, we have started to keep track of samples that corrected with mixing and if we continued to run the confirmatory, what results we recover (like Herb Crown’s study). It will be interesting to see what happens, but so far, after further investigation, we see that the mixing corrects and the confirmatory is positive for patients on LMWH.
Vanessa Chan