UTILIZATION AND COST EFFECTIVENESS OF A RISK STRATIFIED DIAGNOSTIC APPROACH TO PATIENTS WITH SUSPECTED THROMBOTIC THROMBOCYTOPENIC PURPURA

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare but deadly thrombotic microangiopathy (TMA) that is caused by ADAMTS13 deficiency. The PLASMIC clinical scoring system was developed and validated to determine the pretest probability of severe ADAMTS13 deficiency in cases of suspected TTP. We studied the role of the PLASMIC score in guiding use of the ADAMTS13 activity assay and assessed cost of a score-based diagnostic approach to patients with TMA compared to two currently used strategies.
Methods: We utilized an expanded dataset from the Harvard TMA Research Collaborative consisting of n=647 consecutive TMA cases at three large academic medical centers between 2004-2015 for which ADAMTS13 assays were sent. To investigate trends in ADAMTS13 testing over time, we compared the experience at two centers (A and B) with a liberal ADAMTS13 testing policy against a third center in our consortium (C) that carries a more restrictive policy requiring pre-approval by the blood transfusion service. Cost savings analysis was subsequently performed to assess the potential impact of an algorithm incorporating the PLASMIC score for clinical decision support in the workup of these patients.
Results: At Sites A and B, we observed after adjusting for changes in inpatient volume that ADAMTS13 tests increased greater than eight-fold during the study period (from 11 to 94/100,000 admissions between 2004-15, P <0.05). Despite this increase in testing, the average number of patients diagnosed with severe ADAMTS13 deficiency remained steady (5.48 vs 4.67 cases per 100,000 admissions per year for 2004-09 vs 2010-20, p=0.93). Furthermore, stratification of patients by PLASMIC score revealed that low-risk cases accounted for 59% (range: 39-72%) of ADAMTS13 testing (see Figure). By contrast, over the same period of time, Site C did not show a significant increase in ADAMTS13 testing (24 to 22 per 100,000 admissions from 2004-15, p=0.82) and had a steady number of patients with severe ADAMTS13 deficiency (7.96 compared to 5.53 cases per 100,000 admissions per year for 2004-09 vs 2010-15, p=0.83). Site C also had a lower average proportion of patients with low-risk PLASMIC scores who received ADAMTS13 testing each year (39%, range: 0-70%, p=0.004). No patient with a low risk score in our registry was found to have severe ADAMTS13 deficiency between 2004-2015. Cost minimization analysis demonstrates that risk stratification of patients by PLASMIC score to guide use of both testing and therapy would have decreased total costs by 30% ($208,800) in the most recent year studied (2015, n=100 suspected cases) without change in outcomes (see Table).
Conclusions: Our results demonstrate that a significant number of patients at minimal risk for TTP nevertheless undergo ADAMTS13 testing, receive expert consultation and/or TPE. An approach incorporating upfront application of the PLASMIC clinical scoring system to risk stratify patients with suspected TTP may help enhance the cost effectiveness of diagnosing and managing these cases.