TY - CHAP
T1 - Identification of ADAMTS13 inhibitors in acquired TTP
AU - Favaloro, Emmanuel J.
AU - Chapman, Kent
AU - Mohammed, Soma
AU - Vong, Ronny
AU - Pasalic, Leonardo
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13
KW - ADAMTS13
KW - ADAMTS13 inhibitors
KW - Chemiluminescence immunoassay
KW - CLIA
KW - Thrombotic thrombocytopenic purpura
KW - TTP
UR - http://www.scopus.com/inward/record.url?scp=85159757395&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85159757395&partnerID=8YFLogxK
M3 - Chapter (peer-reviewed)
C2 - 37204733
SN - 9781493971947
T3 - Methods in Molecular Biology
SP - 505
EP - 521
BT - Hemostasis and thrombosis
A2 - , Emmanuel J. Favaloro
A2 - , Robert C. Gosselin
PB - Humana Press
CY - New York
ER -