From Bob Dahms, Coagulation Technical Specialist, Long Beach Memorial (first-time user):
I am looking for literature to contraindicate performing factor VIII inhibitor screening and Bethesda titers. I restrict orders for both unless the patient has a factor VIII <20%. Also, post-treatment factor VIII levels of 40-50% have questionable Bethesda titer interpretation. Screening a 9:1 mix at 37 degrees for two hours is also ineffective. There must be some gate keeper recommendations for restricting the application of Bethesda titers. They are time consuming and technical. When are they not appropriate?
A second area of interest is factor IX inhibitor screening. Most reports seem to suggest either 15 minutes incubation at 37 degrees or immediate testing. Any guidance on this issue?
Hello, Bob, and welcome to The Fritsma Factor. In July, 2009 we ran a Quick Question about factor VIII activity level cutoffs for ruling out a Bethesda titer. The response is linked here. You can see there is little consensus, laboratory practitioners use cutoffs from 20 to 50%. I’ve not seen a study that supports one level over another, it may just be a matter of local preference. At University of Alabama at Birmingham we use 30% as our cutoff.
I do think screening is effective, and refer you to a recent comment from Dr. Larry D. Brace, Edward Hospital, Naperville. Dr. Brace prefers a 1:19 dilution. While we use such screens, they are not validated and should be treated as preliminary results to be followed with a Bethesda titer.
Factor IX inhibitors neutralize the factor within five minutes, according to Lechner K: Factor IS inhibitors: report of two cases and a study of the biological, chemical, and immunological properties of the inhjibitors. Thromb Diath Haemorrh 1971;25: 447. You can perform the Bethesda titer assay for factor IX with no incubation.
Again, thank you for your question. Geo.