Use of the ADAMTS13 Activity Assay Improved the Accuracy and Efficiency of the Diagnosis and Treatment of Suspected Acquired Thrombotic Thrombocytopenic Purpura

Abstract

Context.-Acquired thrombotic thrombocytopenic purpura (A-TTP) is a rare but significant disease requiring rapid diagnosis and treatment. The diagnosis is often difficult because of variability in the presence of specific clinical criteria. The primary etiology of A-TTP involves inhibitors directed against ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Literature has shown that the ADAMTS13 activity assay is sensitive and specific for identifying cases of A-TTP, and application of this test as an on-site screening method has not been fully explored.Objective.-Our objective is to determine if the ADAMTS13 activity assay can be used as a successful, on-site diagnostic modality to rapidly identify cases of A-TTP and prevent unnecessary use of prophylactic therapeutic plasma exchange.Design.-A retrospective analysis was performed including 152 patients with clinically suspected A-TTP, screened using the ADAMTS13 activity assay. Results were correlated with potential therapeutic plasma exchange treatment for all cases highly suspicious for A-TTP and evaluated for unnecessary patient morbidity and financial cost.Results.-The ADAMTS13 activity assay had an overall sensitivity and specificity of 100% and 99%, respectively. The positive predictive value was 91% and the negative predictive value was 100%. In 95% of the studies ordered, A-TTP was ruled out, leading to decreased patient morbidity and $1.7 million of potential treatment costs avoided.Conclusion.-Implementation of the fluorescence energy transfer-based ADAMTS13 activity assay as a point-ofcare laboratory study decreased patient morbidity while also directing more efficient employment of therapeutic plasma exchange in cases of suspected A-TTP.

ADAMTS13 test and/or PLASMIC clinical score in management of acquired thrombotic thrombocytopenic purpura: a cost‐effective analysis

“…To our knowledge, this is the first such kind of health economic evaluation on this topic using data and costs from multiple studies in the literature, as well as our own institutional data. Our results are consistent with other studies describing that an in‐house rapid ADAMTS13 assay is more cost‐effective than to send out the test to a reference laboratory . Our results also suggest that the use of PLASMIC score to stratify patients before testing can further improve the cost‐effectiveness of an in‐house assay.…”

“…For example, we assumed that both the in‐house and the send‐out ADAMTS13 tests were FRETS based and, thus, had identical assay performance characteristics. This may not be true since there are other methods measuring ADAMTS13 and/or using different cutoff points from 10% ADAMTS13 activity (as in this evaluation) for distinguishing TTP from other TMAs, which may lead to different sensitivity and specificity parameters between laboratories . It must also be emphasized that the ADAMTS13 results cannot be interpreted correctly without clinical information.…”

Thrombotic thrombocytopenic purpura: pathogenesis, diagnosis and potential novel therapeutics

“…However, normal or mildly reduced plasma ADAMTS‐13 activity may be seen in a variety of hematological or non‐hematological disorders and other types of TMA . A recent study demonstrates that if a cut‐off of ADAMTS‐13 activity < 20 IU dL −1 is used to diagnose TTP, the ADAMTS‐13 test has a sensitivity and specificity of 100% and 99%, respectively, with a positive predictive value of 91% and a negative predictive value of 100% after excluding other conditions such as infection, HPCT and DIC .…”

ADAMTS13 and von Willebrand Factor in Thrombotic Thrombocytopenic Purpura

“…Assays of plasma ADAMTS13 activity and inhibitors help not only in differential diagnosis, but also in stratifying TTP patients for more targeted therapy and in predicting the risk of relapse and long-term outcome (71). When provided in real time, the measurement of plasma ADAMTS13 activity may help to avoid unnecessary plasma-exchange therapy in patients who have other forms of TMA, thereby dramatically reducing overall healthcare costs (72). …”

“…A recent retrospective study suggests that if an ADAMTS13 activity of <20% is used as the cut-off, the diagnostic sensitivity and specificity are 100% and 99%, respectively. The positive predictive value is 91%, and the negative predictive value is 100% (72). …”