” How common is the occurrence of lab error rates in HAE testing? Why would a patient test low C4/C1 inhibitor level years ago and now test within normal range (without patient taking HAE therapies or androgens)”

Mar 28, 2016

Dr. C: I hope everyone had a Happy Easter. I can certainly see where this would be confusing. For the C1 inhibitor testing the answer may lie in how the testing was performed. There are two tests for the C1 inhibitor functional level. The Chromogenic is the most accurate—near 100%. The ELISA technique can demonstrate over 22% equivocal and over 6% normal levels when compared to the Chromogenic for the same patient and sample. In other words you could have a normal test with the ELISA and have HAE. This underscores the value of carefully taking a personal and family history—keep looking for answers, never just rely on a single test. The protein level should also be normal for type II HAE where it would be low for type I. The C4 is more confusing—it is almost always low for HAE type I and II which makes it such a valuable screening tool. Large surveys have placed the chance of a C4 level >50% at <5%. At this time we do not have any diagnostic testing for HAE-nl-C1INH with the exception of the factor XII mutation so our discussion is restricted to Types I and II. Bruce do you have any comments for our reader?


Dr Z: A fundamental principle in medicine is that all unexpected lab tests need to be repeated. In this scenario, we have to ask which results were incorrect, the first set of tests or the second. In general, we would expect C4 and C1 inhibitor antigenic levels to remain low in type I HAE. It is true that normal C4 levels can vary widely in the population; however, this is primarily determined by genetics, which does not change over time. Going back to the results from this patient, there is no such thing as a perfect test. Further, there are multiple areas where problems can occur and lead to tests failing to provide accurate results. Dr. C pointed out the problem with C1INH functional testing. Because the blood complement and contact systems are highly labile, proper handling and storage of the samples once the blood is drawn is important for accurate results. Complement can also be activated as part of a variety of non-HAE diseases, leading to confounding results. In addition, the possibility of human error always needs to be considered. I also agree that the patient’s history is key, and that all tests need to be evaluated in the overall context of the personal and family history.


Dr. C: Thank you Bruce. Dr R is away on vacation but we will look forward to his joining us again next week. I hope that our discussion was helpful for our reader and followers with HAE. We look forward to hearing from you and our next “Question of the Week”.


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