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Identification of ADAMTS13 Inhibitors in Acquired TTP. | LitMetric

Identification of ADAMTS13 Inhibitors in Acquired TTP.

Methods Mol Biol

Haematology Department, Institute of Clinical Pathology and Medical Research (ICPMR), Pathology West, NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia.

Published: May 2023

AI Article Synopsis

  • * Without enough ADAMTS13, VWF accumulates into large multimers, leading to unwanted blood clot formation (thrombosis).
  • * The report outlines a protocol for testing antibodies that inhibit ADAMTS13, using patient plasma in a specialized assay to measure its activity, with a rapid test option available that can yield results in about 35 minutes.

Article Abstract

Thrombotic thrombocytopenic purpura (TTP) is a prothrombotic condition caused by a deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). In turn, ADAMTS13 (also called von Willebrand factor (VWF) cleaving protease (VWFCP)) acts to cleave VWF multimers and thus reduce plasma VWF activity. In the absence of ADAMTS13 (i.e., in TTP), plasma VWF accumulates, in particular as "ultra-large" VWF multimers, and this leads to thrombosis. In most patients with confirmed TTP, ADAMTS13 deficiency is an acquired disorder due to the development of antibodies against ADAMTS13, which either promote clearance of ADAMTS13 from circulation or cause inhibition of ADAMTS13 activity. The current report describes a protocol for assessment of ADAMTS13 inhibitors, being antibodies that inhibit ADAMTS13 activity. The protocol reflects the technical steps that help identify inhibitors to ADAMTS13, whereby mixtures of patient plasma and normal plasma are then tested for residual ADAMTS13 activity in a Bethesda-like assay. The residual ADAMTS13 activity can be assessed by a variety of assays, with a rapid test able to be performed within 35 minutes on the AcuStar instrument (Werfen/Instrumentation Laboratory) used as an example in this protocol.

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Source
http://dx.doi.org/10.1007/978-1-0716-3175-1_33DOI Listing

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