Clinical importance of ADAMTS13 activity during remission in patients with acquired thrombotic thrombocytopenic purpura

Page, Evaren E.; Hovinga, Johanna A. Kremer; Terrell, Deirdra R.; Vesely, Sara K.; George, James N.

doi:10.1182/blood-2016-06-724161

Cited by 78 publications

(81 citation statements)

References 15 publications

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“…Two years after total remission, ADAMTS13 in this chimpanzee continues to be severely deficient, which suggests that, other than in a baboon model, an external factor is necessary to cause TTP . This is similar with human patients, in which it was observed that after clinical remission of acquired TTP, severe ADAMTS13 deficiency was still present in up to 30% of non‐symptomatic patients . Notably, survivors of acute TTP with an ADAMTS13 activity <10% after remission have a threefold greater likelihood of developing another episode of TTP .…”

Section: Discussionsupporting

confidence: 62%

“…To our knowledge, this is the first report of a non-human primate suffering from spontaneous TTP, related to acquired deficiency of ADAMTS13 (defined as <10%). 17 A human assay was able to analyse ADAMTS13 in a deficient and in two healthy chimpanzees, using human reference intervals. The first analysis of ADAMTS13 in this chimpanzee was performed after two-week corticosteroid treatment.…”

Section: Discussionmentioning

confidence: 99%

“…9,10 This is similar with human patients, in which it was observed that after clinical remission of acquired TTP, severe ADAMTS13 deficiency was still present in up to 30% of non-symptomatic patients. 6,17 Notably, survivors of acute TTP with an ADAMTS13 activity <10% after remission have a threefold greater likelihood of developing another episode of TTP. 2 When relapse of TTP symptoms occurs in this chimpanzee, monotherapy with prednisone for at least three weeks is advised.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Thrombotic thrombocytopenic purpura related to ADAMTS13 deficiency, and successful treatment in a chimpanzee (Pan troglodytes verus)

Bolhuis¹,

Wolters²,

Boer

et al. 2017

J of Medical Primatology

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Thrombotic thrombocytopenic purpura related to ADAMTS13 deficiency, and successful treatment in a chimpanzee (Pan troglodytes verus)

Bolhuis¹,

Wolters²,

Boer

et al. 2017

J of Medical Primatology

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“…The introduction of plasma exchange with replacement of fresh frozen plasma – removing antibodies against ADAMTS‐13, VWF, and cytokines, and replenishing ADAMTS‐13 at the same time – led to large numbers of TTP survivors with new problems emerging. The major problem is the risk of relapse, which is almost exclusively seen in patients with severe ADAMTS‐13 deficiency at presentation with the acute episode , and is highest in patients with persistence or reappearance of severe ADAMTS‐13 deficiency in remission . ADAMTS‐13 activity is now increasingly used as a biomarker in the follow‐up of patients and for initiation of pre‐emptive treatment when ADAMTS‐13 activity decreases to values below 10–15% .…”

Section: Ittpmentioning

confidence: 99%

Pathophysiology of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome

Hovinga

Heeb

Skowronska

et al. 2018

Journal of Thrombosis and Haemostasis

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Thrombotic microangiopathies are rare disorders characterized by the concomitant occurrence of severe thrombocytopenia, microangiopathic hemolytic anemia, and a variable degree of ischemic end-organ damage. The latter particularly affects the brain, the heart, and the kidneys. The primary forms, thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), although their clinical presentations often overlap, have distinctive pathophysiologies. TTP is the consequence of a severe ADAMTS-13 deficiency, either immune-mediated as a result of circulating autoantibodies, or caused by mutations in ADAMTS-13. HUS develops following an infection with Shiga-toxin producing bacteria, or as the result of excessive activation of the alternative pathway of the complement system because of mutations in genes encoding complement system proteins.

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“…Even though ADAMTS13 is uniformly severely deficient during an acute episode, there is significant variability of this biomarker during remission, with deficient ADAMTS13 during remission not uniformly being accompanied by relapse. [63][64][65] Being able to determine those at greatest risk of relapse, and other potential risk factors in addition to the ADAMTS13 activity will be key. Different enzymes (including thrombin, plasmin, cathepsin G, neutrophil elastase, proteinase 3, matrix metalloproteinase 9, and granzyme M and B) have been associated with the regulation of VWF and platelet interaction.…”

Section: Future Directionsmentioning

confidence: 99%

Novel therapies in thrombotic thrombocytopenic purpura

Masias

Cataland

2018

Research and Practice in Thrombosis and Haemostasis

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Essentials The standard of care for patients with TTP remains daily plasma exchange in addition to immune suppressive therapy.Despite the improved treatment options for TTP, the acute mortality of TTP remains between 15‐20%.Caplacizumab reduces the time to platelet recovery and the exacerbation rate in acute TTP.A better understanding of the cause and treatments of long‐term complications of TTP are needed. Thrombotic thrombocytopenic purpura (TTP) is characterized by microangiopathic hemolytic anemia and a consumptive thrombocytopenia, as a result of severe deficiency of ADAMTS13. The standard of care of the acute episode is treatment with plasma exchange and immunosuppression. After the acute episode is resolved, patients face a significant risk of relapse and long‐term complications associated with significant morbidity and even mortality. Novel treatments have been under development and will be discussed in this review. Caplacizumab, a nanobody that blocks the interaction between VWF and platelets, has shown promising results in decreasing the time to recover from the acute events that will hopefully translate into long‐term clinical benefit for patients. In addition, identifying biomarkers to allow us to better predict the risk for relapse and the development of these long‐term complications in patients with TTP are a few of the challenges that require our attention moving forward.

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Clinical importance of ADAMTS13 activity during remission in patients with acquired thrombotic thrombocytopenic purpura

Cited by 78 publications

References 15 publications

Thrombotic thrombocytopenic purpura related to ADAMTS13 deficiency, and successful treatment in a chimpanzee (Pan troglodytes verus)

Thrombotic thrombocytopenic purpura related to ADAMTS13 deficiency, and successful treatment in a chimpanzee (Pan troglodytes verus)

Pathophysiology of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome

Novel therapies in thrombotic thrombocytopenic purpura

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