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VWF Reference Interval

From Sharon Johnson, Sysmex America:

Hi George: I was recently asked if guidelines or clinical recommendations had changed for VWF normal ranges based on blood group. In CLSI Guideline H-51A. 2002, it suggests laboratories establish their own reference ranges for VWF for “O” and “Non-O” blood groups, as patients with group “O” typically have much lower normal values. Is there another or newer clinical guideline from ISTH or another hemostasis group that supports one reference range for all blood groups?  I’d appreciate insights from your readers and contributors on this subject.

Hello, Sharon, and thank you for your question, First, it appears that CLSI has dropped H51 as it doesn’t appear in their catalogue, however the most authoritative material on VWD is provided in National Heart, Lung, and Blood Institute. (2009). The Diagnosis, Evaluation, and Management of Von Willebrand Disease. NIH Publication No. 08-5832, Bethesda, MD: US Department of Health and Human Services, National Institutes of Health.This is a freebie from NIH. The prevailing guideline is that we are to establish a single reference interval regardless of blood group. Consequently, the number of “low VWF” people (30–50%) is disproportionately blood group O, but this fits the symptoms–more group O people have mucocutaneous bleeding than the other blood groups. Check also Just, S. (2017) Laboratory testing for von Willebrand disease: the past, present, and future state of play for von Willebrand factor assays that measure platelet binding activity, with or without ristocetin. Semin Thromb Hemost; 43:75–91. I hope this helps.

A same-day response from Sharon: Thank you for your thoughtful response. I downloaded both the NIH and Just documents; the Just article is a fantastic overview of the reagent kits on the market (and more!). For those of us who were taught to create separate references ranges, this is a new, but logical, practice change to better identify VWD.  So much recent information is out there, such as the attached Medscape document, which still advocates the different blood froup-dependent reference ranges. Your blog can help educate laboratorians to set the most informative reference ranges for their facilities.

The Medscape document Sharon cites contains the misleading phrase: “VWF levels should be compared with an ABO blood group type–specific range from the laboratory where the test is performed.” The document is up to date on VWF activity assays, but for some reason it references the obsolete bleeding time test. As a slightly peevish aside, the Medscape document conflates “high-complexity assay” with “difficult to perform,” which has little meaning and is objectionable to laboratory scientists.

Here is the Medscape document, tap or click.

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