Barton, J Cameron; Anderson, Cooper; Miranda, Frida Z; Kelley, Rachel; Kremer Hovinga, Johanna A; Terrell, Deirdra; Vesely, Sara K; George, James N; Muia, Joshua (2023). Cattle-FRETS71, a Novel Fluorogenic Substrate with Broad Applicability for Characterizing ADAMTS13 Properties and Function. Journal of thrombosis and haemostasis, 21(12), pp. 3393-3401. Wiley-Blackwell 10.1016/j.jtha.2023.08.016
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BACKGROUND
Current ADAMTS13 activity assays are important for diagnosing thrombotic thrombocytopenic purpura (TTP) but are unreliable to assay ADAMTS13 activity in animal models. The Cattle-FRETS71 assay is capable of detecting ADAMTS13 activity in plasma from multiple animal species, making it a potentially useful reagent at all stages of clinical research. The performance of Cattle-FRETS71 in TTP diagnosis is not yet known.
AIMS
We evaluated the performance of the Cattle-FRETS71 substrate against the human FRETS-rVWF71 and the FRETS-VWF73 commercial substrates in human plasma and serum samples to validate its utility in diagnosing TTP in patients.
METHODS
Internal validation was performed using heparinized plasma samples (n=81). External validation was a blinded study using serum samples from the Oklahoma TTP Registry (n=118, collected 2004-2014) that had been initially assayed by FRETS-VWF73 within 1 year of collection. Additional validation was done with citrated plasma samples having variable ADAMTS13 activities (n=32) that were analyzed by FRETS-VWF73.
RESULTS
There was an excellent correlation (r=0.94) between Cattle-FRETS71 and FRETS-rVWF71 for assayed heparinized plasma samples (n=81). Assay results between Cattle-FRETS71 and FRETS-VWF73 of Oklahoma TTP Registry serum samples (n=118) as well as of citrated plasma samples (n=32) were comparably good (r=0.81 and r=0.85, respectively).
CONCLUSIONS
The Cattle-FRETS71 assay is comparable with other assays in quantifying ADAMTS13 activity in human plasma collected from patients with documented or suspected TTP. The versatility of Cattle-FRETS71 combined with its specificity and sensitivity, makes it a useful tool for the standardization of ADAMTS13 activity across basic and clinical research paradigms.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory |
UniBE Contributor: |
Kremer Hovinga Strebel, Johanna Anna |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1538-7836 |
Publisher: |
Wiley-Blackwell |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
30 Aug 2023 14:14 |
Last Modified: |
26 Nov 2023 00:14 |
Publisher DOI: |
10.1016/j.jtha.2023.08.016 |
PubMed ID: |
37633642 |
Uncontrolled Keywords: |
ADAMTS13 Animal Models Enzyme Assays TTP von Willebrand Factor |
BORIS DOI: |
|
URI: |
https://boris.unibe.ch/id/eprint/185777 |
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