Development and validation of a predictive model for death in acquired severe ADAMTS13 deficiency-associated idiopathic thrombotic thrombocytopenic purpura: the French TMA Reference Center experience

Benhamou, Y.; Assié, C.; Boëlle, Pierre‐Yves; Buffet, M.; Grillberger, Rana; Malot, Sandrine; Wynckel, Alain; Presne, Claire; Choukroun, Gabriel; Poullin, Pascale; François, Patrice; Gruson, Didier; Hamidou, M.; Bron, Dominique; Pourrat, Jacques; Mira, Jean‐Paul; Guern, Véronique Le; Pouteil‐Noble, Claire; Daubin, Cédric; Vanhille, Philippe; Rondeau, Éric; Palcoux, Jean-Bernard; Mousson, Christiane; Vigneau, Cécile; Bonmarchand, G.; Guidet, Bertrand; Galicier, Lionel; Azoulay, Élie; Rottensteiner, Hanspeter; Veyradier, Agnès; Coppo, Paul

doi:10.3324/haematol.2011.049676

Cited by 126 publications

(112 citation statements)

References 35 publications

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“…The mortality rate for children presenting with acute episodes of A-TTP (8%) has been shown to be similar to that observed in adults (8%-11%). 4,22,23 Clinical criteria remain inadequate for definitive diagnosis of TTP in children and are incapable of differentiating diseases with overlapping presentations such as atypical hemolytic uremic syndrome and Upshaw-Schulman syndrome. 24 The treatments of atypical hemolytic uremic syndrome, UpshawSchulman syndrome, and A-TTP (eculizumab, 25 plasma infusion, and TPE, respectively) are significantly different, requiring rapid results from an ADAMTS13 activity assay to aid in differentiating these diagnoses in the neonatal and pediatric populations.…”

Section: Since Implementation Of the Adamts13 Assay At Texasmentioning

confidence: 99%

Use of the ADAMTS13 Activity Assay Improved the Accuracy and Efficiency of the Diagnosis and Treatment of Suspected Acquired Thrombotic Thrombocytopenic Purpura

Barrows

Teruya

2014

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Acquired thrombotic thrombocytopenic purpura (A-TTP) is a rare but significant disease requiring rapid diagnosis and treatment. The diagnosis is often difficult because of variability in the presence of specific clinical criteria. The primary etiology of A-TTP involves inhibitors directed against ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Literature has shown that the ADAMTS13 activity assay is sensitive and specific for identifying cases of A-TTP, and application of this test as an on-site screening method has not been fully explored.Objective.-Our objective is to determine if the ADAMTS13 activity assay can be used as a successful, on-site diagnostic modality to rapidly identify cases of A-TTP and prevent unnecessary use of prophylactic therapeutic plasma exchange.Design.-A retrospective analysis was performed including 152 patients with clinically suspected A-TTP, screened using the ADAMTS13 activity assay. Results were correlated with potential therapeutic plasma exchange treatment for all cases highly suspicious for A-TTP and evaluated for unnecessary patient morbidity and financial cost.Results.-The ADAMTS13 activity assay had an overall sensitivity and specificity of 100% and 99%, respectively. The positive predictive value was 91% and the negative predictive value was 100%. In 95% of the studies ordered, A-TTP was ruled out, leading to decreased patient morbidity and $1.7 million of potential treatment costs avoided.Conclusion.-Implementation of the fluorescence energy transfer-based ADAMTS13 activity assay as a point-ofcare laboratory study decreased patient morbidity while also directing more efficient employment of therapeutic plasma exchange in cases of suspected A-TTP.

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Section: Since Implementation Of the Adamts13 Assay At Texasmentioning

confidence: 99%

Use of the ADAMTS13 Activity Assay Improved the Accuracy and Efficiency of the Diagnosis and Treatment of Suspected Acquired Thrombotic Thrombocytopenic Purpura

Barrows

Teruya

2014

Archives of Pathology &Amp; Laboratory Medicine

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“…40,41 Forthcoming studies will assess Figure 1. Proposition for the treatment of acute refractory TTP.…”

Section: Future Directions: How To Further Improve the Prognosis In Ttp?mentioning

confidence: 99%

Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange

Coppo

Froissart

2015

Hematology

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Daily therapeutic plasma exchange (TPE) transformed the historically fatal prognosis of acquired, anti-ADAMTS13 antibody-mediated thrombotic thrombocytopenic purpura (TTP), leading to the current overall survival rates of 80%-85%. However, relapses occur in ϳ40% of patients and refractory disease with fatal outcomes still occurs. In this context, the introduction of rituximab has probably been the second major breakthrough in TTP management. Rituximab is now routinely recommended during the acute phase, typically in patients with a suboptimal response to treatment, or even as frontline therapy, with high response rates. In more severe patients, salvage strategies may include twice-daily TPE, pulses of cyclophosphamide, vincristine, as well as splenectomy in more desperate cases.In this life-threatening disease, relapse prevention represents a major goal. Persistent severe acquired ADAMTS13 deficiency in patients who are otherwise in remission is associated with a high risk of relapse and preemptive treatment with rituximab may be considered in this context.In the coming years, the TTP therapeutic landscape should be enriched by original strategies stemming from clinical experience and new agents that are currently being evaluated in large, ideally international, clinical trials. Promising agents under evaluation include N-acetylcysteine, bortezomib, recombinant ADAMTS13, and inhibitors of the glycoprotein-Ib/IX-von Willebrand factor axis. Learning Objectives• Patients with acquired TTP who experience a suboptimal response (refractoriness or disease exacerbation) with standard management need a more intensive treatment • Salvage therapies typically include rituximab, and in the more severe cases twice daily plasma exchange, boluses of cyclophosphamide, vincristine, and splenectomy • A persistent severe acquired ADAMTS13 deficiency during TTP remission should prompt consideration of preemptive rituximab to prevent relapses

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“…Secondary forms of TTP are treated according to the underlying pathology. Treatment of TTP in children is controversial (13)(14)(15). Immunosuppressant drugs such as glucocorticoids, rituximab, cyclophosphamide, vincristine, or cyclosporine may also be used if there is relapse or recurrence following plasmapheresis (5-7), but there are no data from the literature to confirm this utilization in childhood; in our patient treatment with IVIG was effective and more active than plasmpapheresis.…”

Section: Discussionmentioning

confidence: 99%

Intravenous Immunoglobulin Therapy When Plasmapheresis Fails in Thrombotic Thrombocytopenic Purpura Associated with Severe ADAMTS 13 Deficiency in Childhood: A Case Report

et al. 2013

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Thrombotic thrombocytopenic purpura (TTP) is a disorder of the blood-coagulation system, causing extensive microscopic clots to form in the small blood vessels throughout the body. TTP is quite a rare pathology in childhood, being more frequent among adults. Often it is hardly to distinguish from other haematological pathologies in children both for its uncommon incidence and for the presence of clinical forms that are heterogeneous and difficult to classify. We report the case of an ll-year-old girl suffering from TTP, in whom the study of metallo-protease ADAMST 13 showed a low value « 10%) with positive anti-ADAMTS 13 Ig G and inhibitor, strengthening the hypothesis of autoimmune genesis. The girl was initially treated with cycles of plasmapheresis with both poor compliance and benefit for the girl and later treated with IV Immunoglobulin. This last treatment resulted in a rapid improvement of the symptomatology and no reappearance of the clinical signs at four-year follow-up.

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Development and validation of a predictive model for death in acquired severe ADAMTS13 deficiency-associated idiopathic thrombotic thrombocytopenic purpura: the French TMA Reference Center experience

Cited by 126 publications

References 35 publications

Use of the ADAMTS13 Activity Assay Improved the Accuracy and Efficiency of the Diagnosis and Treatment of Suspected Acquired Thrombotic Thrombocytopenic Purpura

Use of the ADAMTS13 Activity Assay Improved the Accuracy and Efficiency of the Diagnosis and Treatment of Suspected Acquired Thrombotic Thrombocytopenic Purpura

Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange

Intravenous Immunoglobulin Therapy When Plasmapheresis Fails in Thrombotic Thrombocytopenic Purpura Associated with Severe ADAMTS 13 Deficiency in Childhood: A Case Report

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