Utilization of testing for common inherited thrombot1c disorders in a reference laboratory

BACKGROUND/OBJECTIVE: Deep-vein thrombosis is a common complication of several inherited and acquired disorders. It is, therefore, important to be able to identify inherited thrombotic disorders in order to successfully prevent possible recurrent venous thrombosis and/or pulmonary embolism in potentially affected family members. Although functional assays are recommended for initial screening for many inherited thrombotic disorders, our reference laboratory offers both functional and nonfunctional tests for several of the more common inherited thrombotic disorders (factor V Leiden [FVL] and protein C, protein S and antithrombin III [ATI11] deficiencies), and a PCR-based assay for detection of the prothrombin O₂0210A mutation. We were interested to determine whether appropriate tests were being requested in order to accurately and efficiently diagnose these five disorders and/or whether the number of orders for each test was consistent with their relative prevalence. METHODOLOGY: We prospectively evaluated laboratory test ordering patterns at ARUP for five common inherited thrombotic disorders (FVL, prothrombin G20210A mutation, and protein C. protein S, and ATHI deficiencies) for up to 20 months from November 1998 through June 2000. RESULTS: The ATHI enzymatic test, a functional assay, was ordered an average of 2.5 times more frequently per month than the ATHI antigen test, while antigenic tests for protein C and protein S were ordered approximately 1.8 and 1.7 times more frequently, respectively, than protein C and protein S functional assays. The FVL PCR test was ordered 3.8 times more frequently per month than the APC resistance assay, a functional assay for the detection of FVL. The number of orders for prothrombin mutation tests was 2.8 times less per month than the ATHI functional assay, even though this mutation is approximately five times more prevalent than ATHI deficiency. CONCLUSIONS: Although functional assays are recommended for screening for protein C, protein S, and ATHI deficiencies, and for detection of FVL, only in the case of ATIII was a functional assay ordered more frequently than a nonfunctional test. In addition, the number of ATIII tests ordered was much greater, and the number of prothrombin mutation tests much less, than warranted by the relative prevalence of each of these disorders. Hematologists and clinical pathologists are in a unique position to guide clinicians in appropriate test ordering for inherited thrombotic disorder identification.