Secondary thrombotic microangiopathy in systemic lupus erythematosus and antiphospholipid syndrome, the role of complement and use of eculizumab: Case series and review of literature

Kello, Nina; Khoury, Lara El; Marder, Galina; Furie, Richard; Zapantis, Ekaterini; Horowitz, Diane

doi:10.1016/j.semarthrit.2018.11.005

Cited by 117 publications

(84 citation statements)

References 58 publications

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“…В ряде работ показана патогенетическая роль антифосфолипидных антител не только в развитии тромботических осложнений у онкологических больных, но и патогенетическая связь заболеваний, связанных с циркуляцией антифосфолипидных антител (осложнения беременности) и последующим обнаружением у этих больных злокачественных новообразований [79−81]. На настоящий момент нет работ, однозначно указывающих на связь антифосфолипидных антител и антител к ADAMTS13, однако имеются данные, что при наличии циркулирующих антифосфолипидных антител реализуются механизмы, ведущие к развитию ТМА за счет участия антифосфолипидных антител в формировании эндотелиопатии [82,83]. Однако эти вопросы остаются предметом дальнейшего изучения.…”

Section: Discussionunclassified

Thrombotic microangiopathy in cancer patients

et al. 2019

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Thrombotic microangiopathy (TMA) is a rare phenomenon, which is severe pathology based on systemic microvascular thrombosis. TMA is characterized by thrombocytopenia and signs of microangiopathic hemolytic anemia. The review presents a modern data on the pathogenesis of tumor-associated thrombotic microangiopathy, considers the interaction of various effectors related to both tumor growth and metastasis process ― immune system activation, endotheliopathy formation, use of chemotherapeutic agents and targeted therapy in the pathogenesis of various forms of TMA. The interaction between the tumor tissue, hemostasis and immune systems are of the type of cascade of mutual activation, thus leading to the formation of a vicious circle, resulting in damage to endothelium and thrombosis in the microcirculatory channel, that is, the development of TMA. The formation of thromboembolism, which includes tumor tissue in the microvessels of the lungs, contributes to the development of pulmonary tumor thrombotic microangiopathy (PTTM). Сancer patients have higher vWF levels and lower ADAMTS13 levels or/and activity than the general population, often also depending on the stage of cancer: vWF and ADAMTS13 have been shown to be associated with thrombotic complications in cancer patients, and ADAMTS13 shows prognostic potential. Increased expression of complement proteins and/or activation of complement during chemotherapy, infectious and inflammatory complications may also cause TMA development. Pathogenesis of thrombotic microangiopathy also is associated with numerous chemotherapeutic agents, such as mitomycin C, gemcitabine, cisplatin, carboplatin and Bevacizumab, an inhibitor of VEGF. This may be the result of both the direct toxic effect of the drug on endothelium and damage of it by immune complexes caused by expression of the VEGF-antibodies. Usage of number of chemotherapeutic agents, especially anti-VEGF and tyrosine kinase inhibitors, which have a direct toxic effect on endothelium, are associated with the development of TMA. Mechanisms causing the development of TMA are considered as components of the hemostasis system, leading to the development of chronic, long-lasting disorders of the hemostasis system (chronic DIC syndrome) and are associated with high incidence of thrombotic complications.

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Section: Discussionunclassified

Thrombotic microangiopathy in cancer patients

et al. 2019

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“…Fallberichte zeigen eine Wirksamkeit bei therapierefraktärer Lupusnephritis [46]. Insbesondere bei der sekundären thrombotischen Mikroangiopathie stellt Eculizumab eine therapeutische Option dar [47].…”

Section: B-zell-hyperaktivitätunclassified

Neue Erkenntnisse zur Pathogenese des SLE und ihre Auswirkungen auf die Entwicklung neuer Therapie-Konzepte

Hiepe

2020

Aktuelle Rheumatologie

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ZusammenfassungAutoantikörper sind essentiell in der Pathogenese des SLE. Sie sind das Ergebnis einer Störung des erworbenen (adaptiven) Immunsystems mit fehlender Toleranz gegen Selbst. Eine Typ-I Interferon-Signatur, die im angeborenen (innaten) Immunsystem ihren Ursprung hat, ist ein wesentlicher Treiber dieser Störung. Autoantikörper können sowohl von kurzlebigen, proliferierenden Plasmablasten, die B-Zell-Hyperaktivität widerspiegeln, als auch von langlebigen, nicht-proliferierenden Gedächtnis-Plasmazellen sezerniert werden. Gedächtnis-Plasmazellen, die in Nischen im Knochenmark und im entzündeten Gewebe lokalisiert sind, lassen sich nicht durch konventionelle Immunsuppressiva und Therapien mit B-Zellen als Target eliminieren. Konzepte, die auf die Depletion von Gedächtnis-Plasmazellen abzielen, können im Zusammenspiel mit Targets, die eine Aktivierung von autoreaktiven B-Zellen verhindern, ein kuratives Potenzial haben.

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“…These data suggest that cohort studies, similar to those used for approval of eculizumab in aHUS, cannot be accepted as proof for efficacy of a drug in secondary TMAs, with the possible exception of patients with life-threatening catastrophic antiphospholipid syndrome, which is, in contrast to other secondary TMAs, characterized by early mortality directly related to systemic TMA. 9 Eculizumab in secondary TMAs: unproven benefit Shiga-toxin producing Escherichia coli-associated HUS (STEC-HUS). During the enterohemorrhagic Escherichia coli outbreak in Germany, >300 patients received eculizumab.…”

Section: Complement Activation Is Not Equivalent To Complement Dysregmentioning

confidence: 99%