Abstract
Background
Historically a diagnosis of thrombotic thrombocytopenic purpura (TTP) was made on autopsy. Following the identification of ADAMTS13 deficiency as central to the pathophysiology of TTP, measurement of the enzyme became a vital diagnostic tool. ADAMTS13 activity can be measured using fluorescence resonance energy transfer (FRET), immunoblotting (IB) or enzyme-linked immunosorbent assay (ELISA). However, such assays have traditionally been performed in only a few selective laboratories nationally. ADAMTS13 testing serves as both a diagnostic investigation for those with suspected TTP, as well as a method of monitoring those at risk of relapse. Due to the diversity in local practice, availability, and reporting of both acute and serial ADAMTS13 measurements, it remains unclear as to what constitutes best practice with regards to frequency of testing and how the test can result best support clinical decision making.
Aim
To review changing trends and patterns in ADAMTS13 testing before and after the set-up of a regional TTP Specialist Centre. To evaluate how this might inform future practice with regards to regional testing provision, patient monitoring and elective Rituximab.
Methods
This was a retrospective study of ADAMTS13 testing from 2011-18. Data was collected using the Trust electronic laboratory software system, instituted in 2011.
The data was reviewed to identify serial trends in testing and in relation to the set-up of a regional TTP Specialist Service provision in 2013.
Results
A total of 2140 ADAMTS13 activity requests for 464 individual patients were performed between January 2011 and January 2018 using the Technoclone ELISA ADAMTS13 activity assay.
A review of the number of ADAMTS13 activity tests performed demonstrated a serial annual rise with total tests per year- 2011: 39, 2012: 88, 2013: 137, 2014: 301, 2015: 401, 2016: 494, 2017: 679. This equated to a 17-fold increase in testing from 2011 compared to 2017, and 5-fold increase from 2013 to 2018 since the set-up of the regional Specialist Service.
External referrals for testing constituted 14% of all ADAMTS13 activity requests with a significant 600% rise in all external requests between 2013 and 2018. These included external requests for analysis from 23 different hospital trusts, with the furthest requesting trust being 54 miles from the regional centre.
65% of external requests represented acute referrals with 35% representing monitoring requests for patients receiving shared care between their local hospital and Specialist Centre.
Of all internal requests, 82% were from haematology followed by critical care and nephrology. In contrast to external requesting, of the internal requests only 5% were for acute diagnosis compared with 95% of requests made for monitoring purposes.
ADAMTS13 activity for monitoring in this patient cohort represented a combination of assessing response to treatment following an acute diagnosis, as well as long term monitoring in remission to identify potential relapse. Internal requests for both acute and monitoring purposes rose annually, with a 20-fold increase in monitoring requests from 2011 to 2017, and a 3-fold increase in acute requests over the same time period.
Conclusions
ADAMTS13 testing has continued to significantly increase annually suggesting a combination of improved diagnostic awareness and increased disease monitoring. The setup of a regional clinical service including laboratory diagnostics results in a significant increase in acute testing requests serving a wide geographic area. In an era where agents are available to potentially avoid acute relapse, more patients are being monitored using serial ADAMTS13 measurements during follow-up. Although avoiding acute clinical relapse has significant implications for the health service and patient mortality, the economics of serial testing in a condition where the enzyme activity is so unpredictable, remains unclear. There is wide variation globally in ADAMTS13 testing and hence a wider evaluation of current practice and outcomes would not only be valuable in establishing greater consensus on best practice, but also inform us more of the natural history of this condition.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
