52 Evaluation of Hereditary Angioedema Testing at a Large Academic Center Reveals Poor Compliance

In 2013, the American Academy of Allergy, Asthma, and Immunology (AAAAI) published a consensus guideline outlining a testing strategy to diagnose hereditary angioedema (HAE). The guideline recommends that tests be ordered sequentially, with serum complement C4 ordered first, followed by C1-inhibitor antigen (C1INH) assay if C4 is low. C1INH function assay is ordered only if C1INH antigen is normal. To examine compliance with the AAAAI guidelines in a large academic medical center. All C1INH antigen and function assays ordered between January 1, 2000 and November 1, 2016 were reviewed. C1INH function assays were only available between June 1, 2010 and November 1, 2016. Compliance with the AAAAI guideline by ordering physicians was measured before and after its publication date (June 2013). Compliance for C1INH antigen was defined as a presence of low serum C4 in patients who received testing for C1INH antigen; normal C4 or no C4 ordered was considered noncompliant. Similarly, compliance for the C1INH function assay was defined as a presence of normal C1INH antigen in patients who were tested for C1INH function assay; low antigen or no antigen ordered was considered noncompliant. The compliance rate for each test was defined as the number of compliant orders divided by the total number of orders. Low values were defined as below the lower limit of the reference interval. When multiple results were available, compliance was assessed using the lowest serum C4 for compliance with C1INH antigen and highest C1INH antigen for compliance with C1INH function assay, to maximize the compliance rate. A total of 1283 C1INH antigen assays from 1147 patients and 506 C1INH function assays from 484 patients were reviewed. Many tests were ordered simultaneously instead of sequentially. Of 1283 C1INH antigen tests, seven patients had two antigen assays performed on the same day (all normal). Of the remaining 1276 tests, 55.7% (771/1276) were ordered at the same time as serum C4. Of the 506 C1INH function tests, 25.2% (128/506) were ordered at the same time as C1INH antigen. Of the 1147 patients tested for C1INH antigen, 782 had serum C4 performed, 106 with low C4 (compliance rate 9.2%, 106/1147). Similarly, of the 484 patients receiving C1INH function assays, 157 had accompanying C1INH antigen tests. However, only 145 C1INH antigen tests were normal (compliance rate 30.0%, 145/484). Compliance rates after the guideline’s publication were slightly higher than before (8.6% before and 14.5% after for C1INH antigen; 22.2% and 38.8% for C1INH function assay). Compliance with the AAAAI guideline for HAE is low. Many of the tests were ordered at the same time, which may have adversely affected the compliance. Further effort should focus on sequential testing, possibly by incorporating an algorithmic testing cascade.