From Kim Kinney, Indiana University Health, Hi George! We have a severe hemophiliac with an 8BU inhibitor receiving ReFacto. Factor assays are high, but dilutions dilute backward! 367, 238, then 183, then 167 causing a CV flag. We have seen this before, but have never heard an explanation for the “backward” dilution affect. Can you shed light? It does not happen on all treated hemophiliacs…is it the ReFacto? Thanks for the info!
Hi, Kim, and thank you for your question. I’m traveling and don’t have access to my usual references until Monday, and I may not have an answer anyway, so I’m posting this in the hopes that others have seen this effect and have an explanation. Stand by, and lets hope for an answer.
More from George on Tuesday, 10/22/13: Kim, again thank you for your question. I still don’t have a definitive answer, but I recall from experience that the one-stage clot-based factor VIII assay generates an unreliable result for ReFacto, as documented in Cauchie M, Toelen J, Peerlinck K, Jacquemin M. Practical and cost-effective measurement of B-domain deleted and full-length recombinant FVIII in the routine haemostasis laboratory. Haemophilia. 2013 May;19:e133-8. The factor assay generates a result that is about half what is expected from dosage and half-life computations. However, this doesn’t explain the backward results, nor does it explain the role of the inhibitor.
Meanwhile, I am curious about why your hematologists choose ReFacto to treat a hemophilic with an inhibitor, given that ReFacto, which is a recombinant B-domain deleted factor VIII concentrate, is likely to bind the inhibitor. Wouldn’t they be inclined to use FEIBA or NovoSeven? Just curious. I hope some of our participants have a more definitive answer, let’s wait and see.
Kim, I contacted Chris Ferrell from University of Washington Medical Center andDave McGlasson from Wilford Hall USAF Medical Center, Lackland AFB, Texas. Both have seen this phenomenon, but neither has a ready explanation, except that it may just reflect the imprecision of the clot-based factor VIII when measuring high levels. Chris has also seen in in chromogenic assays. It does not seem to be specific to ReFacto.
By the way, I’ve been assuming you were describing clot-based assay results, but Chris asks, are these clot-based assay or chromogenic results? She hasn’t seen numbers this high for a clottable factor VIII.