ADAMTS13 conformation is closed in non-immune acquired thrombotic thrombocytopenic purpura of unidentified pathophysiology

Joly, Bérangère S.; Roose, Elien; Coppo, Paul; Vanhoorelbeke, Karen; Veyradier, Agnès

doi:10.3324/haematol.2022.280768

Cited by 6 publications

(20 citation statements)

References 17 publications

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“…Recent reports have highlighted an additional potential mechanism resulting in TTP that is unrelated to the congenital deficiency of or antibodies to ADAMTS13. Changes in ADAMTS13 to a “closed” conformation have been linked to a non-immune form of TTP, in a proposed phenomenon of TTP of unknown pathophysiology, or uTTP ( Figure 1 ) [ 2 , 13 , 14 , 15 , 16 ]. In these cases, cTTP is not present, and antibodies to ADAMTS13 are not detected, leading to this third category [ 13 , 14 , 16 ].…”

Section: Known Mechanisms Laboratory Values and Treatmentmentioning

confidence: 99%

Pathological Mechanisms and Novel Testing Methods in Thrombotic Thrombocytopenic Purpura

Dolin,

Maitta

2024

Biomedicines

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Thrombotic thrombocytopenic purpura (TTP) is an uncommon, but potentially disabling or even deadly, thrombotic microangiopathy with a well-studied mechanism of ADAMTS13 deficiency or dysfunction. While established treatments are largely effective, the standard ADAMTS13 testing required to definitively diagnose TTP may cause delays in diagnosis and treatment, highlighting the need for rapid and effective diagnostic methods. Additionally, the heterogeneous presentation and varied inciting events of TTP suggest more variation in its mechanism than previously thought, implying three potential pathways rather than the accepted two. The recent discovery of ADAMTS13 conformation as a potential contributor to TTP in addition to the proposal of using the absolute immature platelet count (A-IPC) as a biomarker, present novel areas for monitoring and treatment. A-IPC in particular may serve as a more rapid and accurate diagnostic test to distinguish TTP from non-TTP TMAs and to monitor treatment response and relapse. These considerations highlight the need to further study TTP in order to improve best practices and patient care.

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Section: Known Mechanisms Laboratory Values and Treatmentmentioning

confidence: 99%

Pathological Mechanisms and Novel Testing Methods in Thrombotic Thrombocytopenic Purpura

Dolin,

Maitta

2024

Biomedicines

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“…Laboratory features showed less severe thrombocytopenia, higher creatinine values and higher ADAMTS13 antigen levels in uTTP compared to iTTP cases. 1 The ADAMTS13 conformation index, measurable in 59/76 uTTP and in 30/49 iTTP patients with ADAMTS13 antigen levels of ≥0.03 µg/mL displayed an open conformation in 23/30 (76%) cases of iTTP but in only 8/59 (13.6%) uTTP patients.…”

mentioning

confidence: 96%

“…The study by Mariotte et al 7 and the letter by Joly et al 1 suggesting the existence of a third pathophysiological form of TTP besides the well-established iTTP and cTTP, raise scientifically and practically important questions. What might the pathophysiology of uTTP be?…”

mentioning

confidence: 99%

“…Joly et al , on behalf of the French Reference Center for Thrombotic Microangiopathies (CNR-MAT), reiterates the existence of a so-far largely disregarded - not to say «scotomized» - form of acquired thrombotic thrombocytopenic purpura (TTP). 1 In the hundred years since its first description by Moschcowitz in 1924, TTP has attracted the interest of numerous clinicians and researchers; the development of our knowledge on the pathophysiology and more recently new therapeutic advances in this previously mostly fatal disease are a major success story of modern scientific medicine. 2…”

mentioning

confidence: 99%

“…The letter by Joly et al 1 now focuses on the ADAMTS13 conformation in acquired TTP of unknown pathophysiology, tentatively called uTTP. The authors selected a new cohort of 125 adult patients with a first episode of acute non-idiopathic TTP (ADAMTS13 activity <10% of normal) enrolled in the French Thrombotic Microangiopathy Registry between 2012 and 2016.…”

mentioning

confidence: 99%

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