Imperial College London
Alternate

ProfessorJimCrawley

Faculty of Medicine, Department of Immunology and Inflammation

Professor of Haemostasis
 
 
 
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Contact

 

+44 (0)20 3313 2297j.crawley Website

 
 
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Location

 

5S5aCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Underwood:2023:10.1016/j.jtha.2023.02.011,
author = {Underwood, MI and Alwan, F and Thomas, MR and Scully, MA and Crawley, JTB},
doi = {10.1016/j.jtha.2023.02.011},
journal = {Journal of Thrombosis and Haemostasis},
pages = {1544--1552},
title = {Autoantibodies enhance ADAMTS-13 clearance in patients with immune thrombotic thrombocytopenic purpura},
url = {http://dx.doi.org/10.1016/j.jtha.2023.02.011},
volume = {21},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundSevere deficiency in ADAMTS-13 (<10%) and the loss of von Willebrand factor–cleaving function can precipitate microvascular thrombosis associated with thrombotic thrombocytopenic purpura (TTP). Patients with immune-mediated TTP (iTTP) have anti-ADAMTS-13 immunoglobulin G antibodies that inhibit ADAMTS-13 function and/or increase ADAMTS-13 clearance. Patients with iTTP are treated primarily by plasma exchange (PEX), often in combination with adjunct therapies that target either the von Willebrand factor-dependent microvascular thrombotic processes (caplacizumab) or the autoimmune components (steroids or rituximab) of the disease.ObjectivesTo investigate the contributions of autoantibody-mediated ADAMTS-13 clearance and inhibition in patients with iTTP at presentation and through the course of the PEX therapy.Patients/MethodsAnti-ADAMTS-13 immunoglobulin G antibodies, ADAMTS-13 antigen, and activity were measured before and after each PEX in 17 patients with iTTP and 20 acute TTP episodes.ResultsAt presentation, 14 out of 15 patients with iTTP had ADAMTS-13 antigen levels of <10%, suggesting a major contribution of ADAMTS-13 clearance to the deficiency state. After the first PEX, both ADAMTS-13 antigen and activity levels increased similarly, and the anti-ADAMTS-13 autoantibody titer decreased in all patients, revealing ADAMTS-13 inhibition to be a modest modifier of the ADAMTS-13 function in iTTP. Analysis of ADAMTS-13 antigen levels between consecutive PEX treatments revealed that the rate of ADAMTS-13 clearance in 9 out of 14 patients analyzed was 4- to 10-fold faster than the estimated normal rate of clearance.ConclusionThese data reveal, both at presentation and during PEX treatment, that antibody-mediated clearance of ADAMTS-13 is the major pathogenic mechanism that causes ADAMTS-13 deficiency in iTTP. Understanding the kinetics of ADAMTS-13 clearance in iTTP may now enable further optimization of treatment of patients with iTTP.
AU  - Underwood,MI
AU  - Alwan,F
AU  - Thomas,MR
AU  - Scully,MA
AU  - Crawley,JTB
DO  - 10.1016/j.jtha.2023.02.011
EP  - 1552
PY  - 2023///
SN  - 1538-7836
SP  - 1544
TI  - Autoantibodies enhance ADAMTS-13 clearance in patients with immune thrombotic thrombocytopenic purpura
T2  - Journal of Thrombosis and Haemostasis
UR  - http://dx.doi.org/10.1016/j.jtha.2023.02.011
UR  - http://hdl.handle.net/10044/1/103127
VL  - 21
ER  -
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