ADAMTS13 is a plasma protease that cleaves von Willebrand factor (VWF) to prevent the spontaneous interaction of VWF with platelets that can result in microvascular thrombosis. Severe deficiency of ADAMTS13 results in thrombotic thrombocytopenic purpura (TTP), a cause of thrombotic microangiopathy (TMA). TMA, which is characterized by hemolytic anemia, thrombocytopenia and organ dysfunction from microvascular thrombosis, is a serious complication of dysregulated coagulation and complement activation in patients with infections, cancer, autoimmune disorders, pregnancy, organ transplants and other conditions (Chapman et al., 2012).
Autosomal recessive congenital ADAMTS13 deficiency (aka familial/inherited TTP and Upshaw-Schulman syndrome) is caused by biallelic pathogenic variants in the ADAMTS13 gene, with prevalence estimated at 1.1 per million (Zhao et al., 2021). Our esoteric hematology reference laboratory performs plasma testing for ADAMTS13 activity (to diagnose TTP) and ADAMTS13 inhibitor and antibody (to confirm acquired TTP), as well as genetic analysis of ADAMTS13 (to identify genetic etiology among patients with known ADAMTS13 deficiency). Genetic analysis of ADAMTS13 for diagnosis of inherited TTP may be recommended when there is evidence of severe ADAMTS13 deficiency.
As a laboratory stewardship service, our genetic counseling team assesses clinical history provided with incoming genetic test orders and contacts clients when an order change may be beneficial in terms of clinical utility, cost, or turnaround time; orders are only modified or canceled with explicit instruction from clients. Based on disease frequency of congenital ADAMTS13 deficiency, Versiti’s Hematology Genetics team noticed an above average ordering trend for Single Gene ADAMTS13 Analysis from one specific client (“Client A”). In February 2023, our genetic counselors performed a retrospective review of Single Gene ADAMTS13 Analysis orders submitted from Client A over the past five years. Using our stewardship process demonstrated in the flow chart below, the 49 orders placed by Client A in the previous five years were individually reviewed for clinical utility.
