Abstract
Background
Thrombotic thrombocytopenic purpura (TTP) is a rare, life‐threatening thrombotic microangiopathy (TMA), characterized by ADAMTS‐13 activity <10%. ADAMTS‐13 activity assays are typically performed in reference laboratories with a turnaround time of several days. First‐line treatment for TTP, therapeutic plasma exchange (TPE), typically starts while results are pending. The automated, on‐demand HemosIL AcuStar ADAMTS‐13 Activity assay provides results in under an hour, which could reduce unnecessary TPE use and associated costs.
Objectives
To estimate the hospital budget impact in the United States, United Kingdom, and France of using a rapid ADAMTS‐13 activity assay.
Methods
We compared routine use of a rapid assay in adults with TMA with a scenario in which results take 3 days. Model structure and variables were based on published literature, plus survey and interviews of five clinicians from the three countries. Costs for the ADAMTS‐13 activity assays and TPE were included.
Results
Model results suggest that if an on‐demand, rapid ADAMTS‐13 activity assay is used, US, UK, and French hospitals could save $18 million, £1.2 million, and €1.6 million annually, respectively. This equates to $10 788, £3497, and €4700 saved per patient with TMA in the United States, United Kingdom, and France. The model is most sensitive to the exact split of diagnoses of TMA cases, as savings accrue from non‐TTP diagnoses.
Conclusions
In patients with TMA, use of a rapid, on‐demand ADAMTS‐13 activity assay such as the HemosIL AcuStar ADAMTS‐13 Activity assay has the potential to be cost saving for hospitals.
Keywords: ADAMTS‐13 protein, cost savings, plasma exchange, thrombotic microangiopathies, thrombotic thrombocytopenic purpura
Essentials.
ADAMTS‐13 assays are used in the differential diagnosis of thrombotic microangiopathy (TMA).
Patients with TMA receive therapeutic plasma exchange (TPE) while they await assay results.
We modeled the impact of a rapid assay that gives results within an hour rather than days.
The assay could cut TPE use saving $18 million in the United States, £1.2 million in the United Kingdom, and €1.6 million in France annually.
1. INTRODUCTION
Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy (TMA). Differential diagnosis includes atypical (complement‐mediated) hemolytic uremic syndrome (aHUS), Shiga toxin–producing Escherichia coli–associated hemolytic uremic syndrome (STEC‐HUS), or other TMAs caused by conditions such as malignancy or certain medications.
Diagnosis of TTP is time critical, as mortality is 90% without treatment. 1 Guidelines recommend initiating first‐line treatment—therapeutic plasma exchange (TPE)—as soon as TTP is suspected, and ideally within 4 to 8 hours of the patient presenting. 1 , 2
TTP is characterized by low activity levels (<10%) of a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13 (ADAMTS‐13), the von Willebrand factor cleaving protease, in plasma. ADAMTS‐13 activity assays to confirm TTP diagnosis are typically performed in specialized and reference laboratories, as most methods are complex and require specialist skills. 3 , 4 , 5 This can mean a turnaround time (TAT) of several days, due to time taken for sample transport as well as testing and reporting. 6 , 7 As a result, TPE is usually initiated empirically while results are pending.
HemosIL AcuStar ADAMTS‐13 Activity (Instrumentation Laboratory, Bedford MA, USA) is an automated, on‐demand assay with results available in under an hour. Use of this assay could allow more rapid diagnosis of TTP and reduce unnecessary TPE use in patients with other diagnoses, the need to transfer to more specialized hospitals, 8 and the risk of adverse events associated with TPE. Ruling out a TTP diagnosis more rapidly can also allow for earlier initiation of appropriate therapies, potentially improving patient outcomes. For example, earlier initiation of eculizumab in patients with aHUS is associated with a significantly reduced need for dialysis. 9
We estimated the hospital budget impact of routine use of the HemosIL AcuStar ADAMTS‐13 Activity assay on use of TPE in the United States, United Kingdom, and France.
2. METHODS
We compared a rapid TAT scenario using an on‐demand assay versus a standard TAT scenario in which it takes an average of 3 days to receive results. The treatment pathways and model variables were fixed values based on publications plus surveys and interviews with five clinicians from the three countries (see Tables 1 and 2 for details of model input parameters). The survey asked experts to validate assumptions about model parameters and the treatment pathway and suggest values for parameters such as the proportion of individuals with each diagnosis receiving TPE.
TABLE 1.
Population and cost input parameters
| Parameter | Value | Source | Notes |
|---|---|---|---|
| Adult population size (18+ y) |
United States: 256 943 733 United Kingdom: 52 673 433 France: 52 641 954 |
UK Office for National Statistics 20 , 21 French National Institute of Statistics and Economic Studies 22 |
Most recent available data were used:
|
| Annual incidence of TMA | 6.5 per million | Calculation based on Bendapudi et al, 23 Schönermarck et al, 24 Veyradier et al 13 | Same incidence used across study countries |
| Breakdown of individuals with TMA by diagnosis |
23.0% TTP (1.5/m) 13.4% aHUS (0.9/m) 2.3% STEC‐HUS (0.1/m) 61.4% Other (4/m) |
Calculation based on Bendapudi et al 23 and Schönermarck et al 24 | Same breakdown of TMA used across study countries |
| Cost of one TPE treatment |
United States: $5103.70 United Kingdom: £1822.50 France: €3032.05 |
United States: Average of figures from Goshua et al, 25 Connell et al 4 and Kim et al 3 United Kingdom: NHS reference costs 2019 (average of costs for the procedure performed as nonelective short and elective or long stays) 26 plus cost for Octaplas 27 (14 units estimated 7 ) France: Public hospital tariff for plasma exchange from ATIH (tariff for GHS9615 GHM28Z16Z) 28 plus costs for fresh frozen plasma (F. Provôt, personal communication) |
Older cost estimates inflated to 2019 values using medical care inflation rates |
| Cost per HemosIL AcuStar ADAMTS‐13 Activity test |
United States: $500 United Kingdom: £365.69 France: €412.98 |
Instrumentation Laboratory, personal communication | Average cost provided in $ and converted to £ and € using xe.com |
| Cost per standard ADAMTS‐13 activity test |
United States: $312.62 United Kingdom: £100 France: €89 |
United States: Average of figures from Connell et al, 4 Kim et al, 12 Kim et al 3 United Kingdom: University College London Hospitals (Health Services Laboratories) 29 France: Eurofins Biomnis 30 |
Older cost estimates inflated to 2019 values using medical care inflation rates |
Abbreviations: aHUS, atypical (complement‐mediated) hemolytic uremic syndrome; ATIH, Agence Technique de l’Information sur l’Hospitalisation; NHS, National Health Service; STEC‐HUS, Shiga toxin–producing Escherichia coli–associated hemolytic uremic syndrome; TMA, thrombotic microangiopathy; TPE, therapeutic plasma exchange; TTP, thrombotic thrombocytopenic purpura.
TABLE 2.
Percentage of patients with each diagnosis receiving TPE and duration of TPE in standard and rapid turnaround time (TAT) scenarios for each country*
| Diagnoses | US | UK | France | |||
|---|---|---|---|---|---|---|
| Standard TAT scenario | Rapid TAT scenario | Standard TAT scenario | Rapid TAT scenario | Standard TAT scenario | Rapid TAT scenario | |
| TTP | 100%, 3 days | 100%, 3 days | 100%, 3 days | 100%, 3 days | 100%, 3 days | 100%, 3 days |
| aHUS | 100%, 3 days | 10.3%, 3 days | 100%, 3 days | 50%, 3 days | 100%, 3 days | 100%, 3 days |
| STEC‐HUS | 100%, 2 days | 10.3%, 2 days | 100%, 2 days | 50%, 2 days | 100%, 3 days | 100%, 3 days |
| Other diagnoses | 100%, 3 days | 5%, 3 days | 100%, 3 days | 0%, 0 days | 100%, 3 days | 10%, 3 days |
Abbreviations: aHUS, atypical (complement‐mediated) hemolytic uremic syndrome; STEC‐HUS, Shiga toxin–producing Escherichia coli–associated hemolytic uremic syndrome; TAT, turnaround time; TPE, therapeutic plasma exchange; TTP, thrombotic thrombocytopenic purpura.
The model includes all adults hospitalized with TMA (due to TTP, aHUS, STEC‐HUS, or other TMA diagnoses that would need differential diagnosis). The incidence of these conditions was assumed to be the same across all study countries. Population estimates used the most recent available data for each country. The proportion of patients with each diagnosis who received TPE and the duration for which this was received was based on expert responses to the survey. Costs to the hospital are for ADAMTS‐13 activity assays and for any TPE received over 3 days. Cost estimates were obtained from the literature or national cost databases where available, with additional information obtained from expert personal communication and from the HemosIL AcuStar ADAMTS‐13 Activity test manufacturer (Instrumentation Laboratory). Older cost estimates inflated to 2019 values using medical care inflation rates.
Based on guideline recommendations 1 , 10 , 11 and expert confirmation, we assumed that all patients with TMA would receive TPE until TTP was excluded based on the ADAMTS‐13 assay result and clinical judgment. In the standard TAT scenario, it was assumed that most patients would receive TPE for 3 days, as used in previous modeling, 12 and consistent with expert responses in our survey. The US and UK experts indicated that tests to confirm STEC‐HUS diagnosis would be expected back in 2 days, so for these countries it was assumed that TPE would be stopped after 2 days in patients with STEC‐HUS.
In the rapid TAT scenario, it was assumed that once TTP was excluded, a decision on whether to initiate TPE would be based on clinical judgment. The rates of TPE use for each diagnosis were based on average expert estimations for each country. We conservatively assumed that patients with STEC‐HUS would receive TPE at the same rates as those with aHUS until the results of the STEC‐HUS test were received.
Modeling was carried out in Excel (Microsoft Corporation, Redmond, WA, USA). One‐way sensitivity analyses were carried out for key variables where the literature or survey indicated uncertainty or variation in practice. A Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was completed for the study and is available from the corresponding author on request.
3. RESULTS AND DISCUSSION
3.1. Base case results
Model results are summarized in Table 3. The rapid TAT scenario prevents 1215 people from having unnecessary TPE in the United States (3611 treatments), 238 people (711 treatments) in the United Kingdom, and 190 people (570 treatments) in France. This results in total savings nationally for US, UK, and French hospitals of $18 million, £1.2 million, and €1.6 million annually, respectively.
TABLE 3.
Summary of results of the model base case
| US | UK | France | |
|---|---|---|---|
| Total cases of TMA | 1678 | 344 | 344 |
| TTP cases | 385 | 79 | 79 |
| aHUS cases | 225 | 46 | 46 |
| STEC‐HUS cases | 38 | 8 | 8 |
| Other TMA diagnoses | 1030 | 211 | 211 |
| Number of patients avoiding unnecessary TPE | 1215 | 238 | 190 |
| Number of TPE treatments prevented | 3611 | 711 | 570 |
| Savings per patient with TMA | $10,788 | £3479 | €4700 |
| Savings for a hospital serving a catchment area with 1m adults | $70,496 | £22,854 | €30,710 |
| Total annual savings nationally | $18m | £1.2m | €1.6m |
Abbreviations: aHUS, atypical (complement‐mediated) hemolytic uremic syndrome; STEC‐HUS, Shiga toxin–producing Escherichia coli–associated hemolytic uremic syndrome; TMA, thrombotic microangiopathy; TPE, therapeutic plasma exchange; TTP, thrombotic thrombocytopenic purpura.
3.2. Results of sensitivity analyses
One‐way sensitivity analyses were conducted evaluating the impact of:
TPE not being performed for any patients with non‐TTP diagnoses after TTP is excluded in the rapid scenario.
TTP being more common and “other” diagnoses less common.
Reducing the proportion of patients with “other” diagnoses who have ADAMTS‐13 activity testing.
Varying the percentage of patients with HUS who receive TPE after TTP is excluded.
Table 4 summarizes the results of these sensitivity analyses.
TABLE 4.
Results of sensitivity analyses (annual national savings)
| Scenario | United States | United Kingdom | France |
|---|---|---|---|
| (1) No TPE initiated after TTP excluded | $19.3 million | £1.3 million | €2.3 million |
| (2) TTP accounts for 50% TMAs, and “other” 34% | $11.5 million | £0.7 million | €0.9 million |
| (3) Only 50% of “other” diagnoses get ADAMTS‐13 activity test | $10.7 million | $0.7 million | €0.8 million |
| (4) % with aHUS who get TPE after TTP ruled out (ranges from country experts except for France) |
High estimate (31%): $17.3 million Low estimate (0%): $18.5 million |
High estimate (100%): £1.1 million Low estimate (0%): £1.3 million |
High estimate not applicable (100% used in base case) Low estimate (0%): €2.1 million |
Abbreviations: aHUS, atypical (complement‐mediated) hemolytic uremic syndrome; TMA, thrombotic microangiopathy; TPE, therapeutic plasma exchange; TTP, thrombotic thrombocytopenic purpura.
If TPE is not initiated for any patient in whom TTP is excluded after ADAMTS‐13 activity testing, this increases savings to $19.3 million in the United States, £1.3 million in the United Kingdom, and €2.3 million in France. This represents the maximum savings possible in the model (if all other parameters remain constant).
We selected an incidence of 1.5 per million for TTP in our base case, as reported by the French National Reference Center for Thrombotic Microangiopathies, which collects data on all TTP cases nationally. 13 This is a relatively low incidence for TTP, with estimates of up to 3.5 per million in the United States 14 and 6 per million in the United Kingdom. 15 Solely increasing the incidence of TTP in the model would not have a large impact as TPE use for these patients does not differ between the two scenarios.
Therefore, we looked at the impact of keeping the overall incidence of TMA the same, but increasing the proportion of TMA cases that were TTP (from 23% to 50%, ie, to about 3.3 per million) and reducing the proportion of “other” diagnoses (from 61% to 34%, ie, to about 2.2 per million). This reduced savings by between 36% and 47% across the countries.
Experienced clinicians may be able to exclude TTP for some patients based on clinical judgment, without the need for ADAMTS‐13 activity testing. This may particularly be the case for those with “other” TMA diagnoses that are, for example, secondary to malignancy or use of certain medications. If only 50% of those with “other” diagnoses require ADAMTS‐13 activity testing, this reduces savings by 41% to 51%. (Reducing the incidence of “other” diagnoses by 50% would have the same effect.)
Finally, less use of TPE in the aHUS group led to reduced savings, and more use of TPE led to increased savings, but differences were not substantial.
3.3. Limitations and considerations
In some more specialized hospitals, rapid tests are already in use, so some of the estimated savings will already have been recognized. Hospitals that do not currently have the instrumentation to perform rapid tests would have an initial capital investment for the equipment. This was not included in the model for several reasons. National figures on what proportion of hospitals already have the Hemosil AcuStar are not available. Also, the instrumentation can perform multiple different tests and not solely the ADAMTS‐13 assay; therefore, costs would need to be considered across the range of tests for which it is used and for the life span of the equipment, rather than solely for the ADAMTS‐13 assay within the single year covered by our model.
Our base case assumption of an average 3‐day turnaround for standard testing has been used in other analyses 12 and was validated in our expert survey. Turnaround times of up to a week or longer for reference laboratory testing have been reported in some literature. 4 , 9 , 11 Longer turnaround times for standard testing would mean greater potential savings with rapid testing.
There is uncertainty in several of the variables used in the model. TTP is rare, and there are limited national‐level data on its incidence. There are also very limited published estimates of the breakdown of TMAs by diagnosis. In addition, practice is likely to vary between different hospitals nationally and internationally (as indicated in our expert survey). We also surveyed only a small sample of clinicians.
The final diagnosis of TTP is clinical, and the model assumes that clinical diagnosis is accurate regardless of the assay used, as it will be based on overall clinical picture and not solely assay results. A high level of agreement has been reported between the Hemosil AcuStar ADAMTS13 Activity and other ADAMTS13 activity assays, with sensitivity ranging from 90.1% to 100%, and specificity from 94.6% to 100%. 5 , 16 , 17 If in some cases clinical picture is not consistent with rapid assay results, additional ADAMTS‐13 activity testing through reference laboratories may be needed. 16
4. CONCLUSION
In patients with TMA, use of a rapid, on‐demand ADAMTS‐13 activity assay such as the HemosIL AcuStar ADAMTS‐13 Activity assay has the potential to be cost saving for hospitals.
The findings of our model are consistent with other studies that have also suggested that rapid turnaround ADAMTS‐13 activity assays can produce cost savings through reducing TPE use. 3 , 7 , 12
RELATIONSHIP DISCLOSURE
The research was funded by Instrumentation Laboratory, but the Economist Intelligence Unit (EIU) maintained editorial independence throughout. All authors are (or were at the time of the research) employed by the EIU, who receive funding for projects from commercial companies such as Instrumentation Laboratory.
AUTHOR CONTRIBUTIONS
RC conceptualized and supervised the study. AW developed and ran the model. RM provided clinical input on the patient pathway to inform model structure, identified data points, and performed model checking. KS assisted in identification of experts and data points. AS managed the study and provided feedback on the model. All authors assisted in development of the expert survey and contributed to the final manuscript.
ACKNOWLEDGMENTS
We thank the clinicians who kindly gave their time to take part in our survey and interviews: Sue Pavord and Jean‐Paul Westwood, United Kingdom; Francois Provôt, France; X. Long Zheng, Spero Cataland, and Ronald Go, United States. Thanks also to Caroline Coomber for performing the initial literature searches. Views expressed in this article are those of the Economist Intelligence Unit and do not necessarily reflect the views of the clinicians interviewed or the study funders.
White A, Martin R, Sew K, Stucke A, Cook R. Economic impact of a rapid, on‐demand ADAMTS‐13 activity assay for the diagnosis of thrombotic thrombocytopenic purpura. Res Pract Thromb Haemost. 2022;6:e12711. doi: 10.1002/rth2.12711
Handling Editor: Dr Johnny Mahlangu
Funding information
Research was funded by Instrumentation Laboratory.
REFERENCES
- 1. Scully M, Hunt BJ, Benjamin S, et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158(3):323‐335. [DOI] [PubMed] [Google Scholar]
- 2. Azoulay E, Bauer PR, Mariotte E, et al. Expert statement on the ICU management of patients with thrombotic thrombocytopenic purpura. Intensive Care Med. 2019;45(11):1518‐1539. [DOI] [PubMed] [Google Scholar]
- 3. Kim CH, Simmons SC, Wattar SF, et al. Potential impact of a delayed ADAMTS13 result in the treatment of thrombotic microangiopathy: an economic analysis. Vox Sang. 2020;115(5):433‐442. [DOI] [PubMed] [Google Scholar]
- 4. Connell NT, Cheves T, Sweeney JD. Effect of ADAMTS13 activity turnaround time on plasma utilization for suspected thrombotic thrombocytopenic purpura. Transfusion. 2016;56(2):354‐359. [DOI] [PubMed] [Google Scholar]
- 5. Valsecchi C, Mirabet M, Mancini I, et al. Evaluation of a new, rapid, fully automated assay for the measurement of ADAMTS13 activity. Thromb Haemost. 2019;119(11):1767‐1772. [DOI] [PubMed] [Google Scholar]
- 6. Martin IW, Katus MC, Martin CLB, et al. Rapid ADAMTS13 availability impacts treatment for microangiopathic hemolytic anemia and thrombocytopenia. J Clin Apheresis. 2016;31(5):419‐422. [DOI] [PubMed] [Google Scholar]
- 7. Thomas W, Cutler JA, Moore GW, et al. The utility of a fast turnaround ADAMTS13 activity in the diagnosis and exclusion of thrombotic thrombocytopenic purpura. Br J Haematol. 2019;184(6):1026‐1032. [DOI] [PubMed] [Google Scholar]
- 8. Nixon CP, Cheves TA, Sweeney JD. Availability of an ADAMTS13 assay with rapid turnaround time may avoid interhospital transfer in patients with thrombotic microangiopathy. Transfusion. 2018;58(5):1328‐1329. [DOI] [PubMed] [Google Scholar]
- 9. Ryan M, Donato BMK, Irish W, et al. Economic impact of early‐in‐hospital diagnosis and initiation of eculizumab in atypical haemolytic uraemic syndrome. Pharmacoeconomics. 2020;38(3):307‐313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2496‐2502. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Go RS, Winters JL, Leung N, et al. Thrombotic microangiopathy care pathway: a consensus statement for the Mayo Clinic Complement Alternative Pathway‐Thrombotic Microangiopathy (CAP‐TMA) Disease‐Oriented Group. Mayo Clin Proc. 2016;91(9):1189‐1211. [DOI] [PubMed] [Google Scholar]
- 12. Kim CH, Simmons SC, Williams ILA, et al. ADAMTS13 test and/or PLASMIC clinical score in management of acquired thrombotic thrombocytopenic purpura: a cost‐effective analysis. Transfusion. 2017;57(11):2609‐2618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Veyradier A. TPP: Epidemiology of the CNR_MAT Cohort Aged Over 16 Years (PTT : Épidémiologie de la Cohorte du CNR‐MAT sur 16 ans). Centre National de Référence ‐ Microangiopathies Thrombotiques (CNR‐MAT); 2015. https://www.cnr‐mat.fr/le‐centre‐cnr‐mat/organisation/reunions‐annuelles‐du‐centre‐de‐reference/reunion‐du‐centre‐de‐reference‐2015.html [Google Scholar]
- 14. Staley EM, Cao W, Pham HP, et al. Clinical factors and biomarkers predict outcome in patients with immune‐mediated thrombotic thrombocytopenic purpura. Haematologica. 2019;104(1):166‐175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Scully M, Yarranton H, Liesner R, et al. Regional UK TTP registry: correlation with laboratory ADAMTS 13 analysis and clinical features. Br J Haematol. 2008;142(5):819‐826. [DOI] [PubMed] [Google Scholar]
- 16. Beranger N, Benghezal S, Joly BS, et al. Diagnosis and follow‐up of thrombotic thrombocytopenic purpura with an automated chemiluminescent ADAMTS13 activity immunoassay. Res Pract Thromb Haemost. 2020;5(1):81‐93. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Pascual C, Nieto JM, Fidalgo T, et al. Multicentric evaluation of the new HemosIL Acustar® chemiluminescence ADAMTS13 activity assay. Int J Lab Hematol. 2021;43(3):485‐493. [DOI] [PubMed] [Google Scholar]
- 18. United States Census Bureau . U.S. and World Population Clock. U.S. Department of Commerce; June 22, 2020. Cited June 29, 2020. https://www.census.gov/popclock/ [Google Scholar]
- 19. United States Census Bureau . National Population by Characteristics: 2010‐2019. United States Census Bureau; June 17, 2020. Cited March 15, 2021. https://www.census.gov/data/tables/time‐series/demo/popest/2010s‐national‐detail.html [Google Scholar]
- 20. Office for National Statistics . United Kingdom Population Mid‐Year Estimate. Office for National Statistics; June 24, 2020. Cited March 15, 2021. https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/timeseries/ukpop/pop [Google Scholar]
- 21. Office for National Statistics . Estimates of the Population for the UK, England and Wales, Scotland and Northern Ireland. Office for National Statistics; June 24, 2020. Cited March 15, 2021. https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/populationestimatesforukenglandandwalesscotlandandnorthernireland [Google Scholar]
- 22. INSEE . [Demographic Review 2019]. Institut National de la Statistique et des Études Économiques; January 14, 2020. Cited March 15, 2021. [Google Scholar]
- 23. Bendapudi PK, Li A, Hamdan A, et al. Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative. Br J Haematol. 2015;171(5):836‐844. [DOI] [PubMed] [Google Scholar]
- 24. Schönermarck U, Ries W, Schröppel B, et al. Relative incidence of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome in clinically suspected cases of thrombotic microangiopathy. Clin Kidney J. 2020;13(2):208‐216. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Goshua G, Gokhale A, Hendrickson JE, et al. Cost savings to hospital of rituximab use in severe autoimmune acquired thrombotic thrombocytopenic purpura. Blood Adv. 2020;4(3):539‐545. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. NHS England, NHS Improvement . National Cost Collection 2019. NHS England and NHS Improvement. Cited March 19, 2021. https://www.england.nhs.uk/national‐cost‐collection/#ncc1819 [Google Scholar]
- 27. Joint Formulary Committee . British National Formulary. BMJ Group and Pharmaceutical Press; Mar 4, 2021. Cited Mar 19, 2021. https://bnf.nice.org.uk/ [Google Scholar]
- 28. ATIH . [MCO and HAD Tariffs]. Agence Technique de l'Information sur l'Hospitalisation (ATIH); March 3, 2020. Cited March 19, 2021. https://www.atih.sante.fr/tarifs‐mco‐et‐had [Google Scholar]
- 29. University College London Hospitals . ADAMTS13 Information: ADAMTS13 Assay Request Form. UCLH. Cited March 19, 2021. https://www.uclh.nhs.uk/our‐services/find‐service/cancer‐services/blood‐diseases‐clinical‐haematology/blood‐diseases‐types‐and‐services/red‐cell‐diseases/TTP/united‐kingdom‐thrombotic‐thrombocytopenic‐purpura‐ttp‐registry/adamts13‐information [Google Scholar]
- 30. Eurofins Biomnis . [ADAMTS13 ‐ Willebrand Factor Protease]. Eurofins Biomnis. Cited March 19, 2021. https://www.eurofins‐biomnis.com/services/referentiel‐des‐examens/page/ADAM/ [Google Scholar]