High prevalence of infectious events in thrombotic thrombocytopenic purpura and genetic relationship with toll‐like receptor 9 polymorphisms: experience of the <scp>F</scp>rench <scp>T</scp>hrombotic <scp>M</scp>icroangiopathies <scp>R</scp>eference <scp>C</scp>enter

Morgand, Marjolaine; Buffet, M.; Busson, Marc; Loiseau, Pascale; Malot, Sandrine; Amokrane, Kahina; Fortier, Catherine; London, Jonathan; Bonmarchand, G.; Wynckel, Alain; François, Patrice; Poullin, Pascale; Vanhille, Philippe; Presne, Claire; Bron, Dominique; Girault, Stéphane; Delmas, Yahsou; Hamidou, M.; Mousson, Christiane; Vigneau, Cécile; Lautrette, Alexandre; Pourrat, Jacques; Galicier, Lionel; Azoulay, Élie; Pène, Frédéric; Mira, Jean‐Paul; Rondeau, Éric; Ojeda-Uribe, Mario; Charron, Dominique; Maury, Éric; Guidet, Bertrand; Veyradier, Agnès; Tamouza, Ryad; Coppo, Paul

doi:10.1111/trf.12263

Cited by 33 publications

(29 citation statements)

References 32 publications

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“…Exacerbations of aTTP not only re‐expose patients to the increased risk of morbidity and mortality, they also lead to readmission and resumption of daily TPE, and its complications . Thus, prevention of exacerbations is paramount.…”

Section: Resultsmentioning

confidence: 99%

Efficacy and safety of open‐label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study

Knoebl

Cataland

Peyvandi

et al. 2020

Journal of Thrombosis and Haemostasis

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Background: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, lifethreatening autoimmune thrombotic microangiopathy. Caplacizumab, an anti-von Willebrand Factor Nanobody ® , is effective for treating aTTP episodes and is well tolerated. Objectives and methods:In the phase 3 HERCULES trial (NCT02553317), patients with aTTP received double-blind caplacizumab or placebo during daily therapeutic plasma exchange (TPE) and for ≥30 days thereafter. Patients who experienced an exacerbation while on blinded study drug treatment switched to receive open-label caplacizumab plus re-initiation of daily TPE. Exacerbations were defined as recurrence of disease occurring within 30 days after cessation of daily TPE.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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Section: Resultsmentioning

confidence: 99%

Efficacy and safety of open‐label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study

Knoebl

Cataland

Peyvandi

et al. 2020

Journal of Thrombosis and Haemostasis

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“…In the French TTP registry, 41% had infections at diagnosis. 6 Viruses such as HIV, human parvovirus B19, and hepatitis C virus are known to be associated with TTP. [7][8][9] Dengue virus infection, however, is not a recognized trigger of TTP.…”

Section: Discussionmentioning

confidence: 99%

Dengue Virus Infection Triggering Thrombotic Thrombocytopenic Purpura in Pregnancy

Deepanjali

Naik

Mailankody

et al. 2015

The American Society of Tropical Medicine and Hygiene

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Abstract. We report a case of thrombotic thrombocytopenic purpura (TTP) that immediately followed symptomatic dengue virus infection in a pregnant lady. The patient developed dengue fever at 16 weeks of gestation, resulting in spontaneous abortion. Subsequently, fever reappeared with persistent thrombocytopenia and jaundice. Investigations revealed microangiopathic hemolysis; there was no evidence of disseminated intravascular coagulation. The TTP episode resolved after six cycles of therapeutic plasma exchange with fresh-frozen plasma. An ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif 13 repeats) activity assay, done during convalescence, showed normal activity. The patient had an uneventful second pregnancy and has remained free of TTP recurrence for more than 2 years now. We review the pathophysiological basis of TTP in dengue infection, and suggest that jaundice with disproportionate elevation of serum aspartate aminotransferase level in a patient with dengue should arouse the suspicion of TTP.

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“…First, infectious agents can be precipitating factors in patients with a severe ADAMTS13 deficiency, through endothelial activation. No specific agents could be identified, 86 as opposed to HUS, which was typically associated to specific strains of the bacteria Escherichia coli . Endothelial activation in this context may involve nucleosomes that derive at least in part from neutrophil extracellular traps (NETS), networks made of nuclear DNA, histones, granular and cytoplasmic proteins that are released by neutrophils in response to infections.…”

Section: Introductionmentioning

confidence: 99%

“…Variants of the anti-infectious innate immunity sensor Toll-like receptor (TLR)-9 were reported to be more represented in iTTP patients negative for the HLA-DRB1*11 Class II susceptibility allele. 86 TLR-9 harboring specific variants could, therefore, be more prone to activate endothelial and polymorphonuclear cells and produce Th1 cytokines in a context of infection, precipitating an iTTP episode. 86 Similarly, anecdotal responses in patients with severe iTTP following the administration of the complement blocker eculizumab suggest a role for complement deregulation in iTTP pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

Dissecting the pathophysiology of immune thrombotic thrombocytopenic purpura: interplay between genes and environmental triggers

et al. 2018

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Although outstanding progress has been made in understanding the pathophysiology of thrombotic thrombocytopenic purpura (TTP), knowledge of the immunopathogenesis of the disease is only at an early stage. Anti-ADAMTS13 auto-antibodies were shown to block proteolysis of von Willebrand factor and/or induce ADAMTS13 clearance from the circulation. However, it still remains to identify which immune cells are involved in the production of anti-ADAMTS13 autoantibodies, and therefore account for the remarkable efficacy of the B-cell depleting agents in this disease. The mechanisms leading to the loss of tolerance of the immune system towards ADAMTS13 involve the predisposing genetic factors of the human leukocyte antigen class II locus DRB1*11 and DQB1*03 alleles as well as the protective allele DRB1*04, and modifying factors such as ethnicity, sex and obesity. Future studies have to identify why these identified genetic risk factors are also frequently to be found in the healthy population although the incidence of immune-mediated thrombotic thrombocytopenic purpura (iTTP) is extremely low. Moreover, the development of recombinant ADAMTS13 opens a new therapeutic era in the field. Interactions of recombinant ADAMTS13 with the immune system of iTTP patients will require intensive investigation, especially for its potential immunogenicity. Better understanding of iTTP immunopathogenesis should, therefore, provide a basis for the development of novel therapeutic approaches to restore immune tolerance towards ADAMTS13 and thereby better prevent refractoriness and relapses in patients with iTTP. In this review, we address these issues and the related challenges in this field.

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High prevalence of infectious events in thrombotic thrombocytopenic purpura and genetic relationship with toll‐like receptor 9 polymorphisms: experience of the French Thrombotic Microangiopathies Reference Center

Abstract: Infections should be considered as an aggravating factor during the course of TTP. Particular polymorphisms in TLR-9 gene may represent risk factors for TTP.

Cited by 33 publications

References 32 publications

Efficacy and safety of open‐label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study

Efficacy and safety of open‐label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study

Dengue Virus Infection Triggering Thrombotic Thrombocytopenic Purpura in Pregnancy

Dissecting the pathophysiology of immune thrombotic thrombocytopenic purpura: interplay between genes and environmental triggers

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