Successful therapeutic plasma exchange in a 3.2‐kg body weight neonate with atypical hemolytic uremic syndrome

Park

Pediatrics International

et al. 2015

Section: Methodsmentioning

confidence: 99%

Atypical hemolytic uremic syndrome: Korean pediatric series

Park

Pediatrics International

et al. 2015

“…Although the guidelines recommend plasma exchange [ 1 , 3 ], low total blood volume and difficult vascular access make plasmapheresis technically challenging in infants; therefore, this therapeutic option is seldom used [ 21 , 22 ]. Fresh frozen plasma transfusion is an alternative option, but this treatment will not eliminate potentially harmful components and as in our cases, patients often do not respond to FFP.…”

Section: Discussionmentioning

confidence: 99%

First-line therapy in atypical hemolytic uremic syndrome: consideration on infants with a poor prognosis

et al. 2014

BackgroundAtypical hemolytic uremic syndrome (aHUS) is a rare and heterogeneous disorder. The first line treatment of aHUS is plasma therapy, but in the past few years, the recommendations have changed greatly with the advent of eculizumab, a humanized monoclonal anti C5-antibody. Although recent recommendations suggest using it as a primary treatment for aHUS, important questions have arisen about the necessity of immediate use of eculizumab in all cases. We aimed to draw attention to a specific subgroup of aHUS patients with rapid disease progression and high mortality, in whom plasma therapy may not be feasible.MethodsWe present three pediatric patients of acute complement-mediated HUS with a fatal outcome. Classical and alternative complement pathway activity, levels of complement factors C3, C4, H, B and I, as well as of anti-factor H autoantibody and of ADAMTS13 activity were determined. The coding regions of CFH, CFI, CD46, THBD, CFB and C3 genes were sequenced and the copy number of CFI, CD46, CFH and related genes were analyzed.ResultsWe found severe activation and consumption of complement components in these patients, furthermore, in one patient we identified a previously not reported mutation in CFH (Ser722Stop), supporting the diagnosis of complement-mediated HUS. These patients were not responsive to the FFP therapy, and all cases had fatal outcome.ConclusionTaking the heterogeneity and the variable prognosis of atypical HUS into account, we suggest that the immediate use of eculizumab should be considered as first-line therapy in certain small children with complement dysregulation.

“…This situation might explain why HUS frequently develops after an infection 1 3 7) . The therapeutic strategies that are used to treat atypical HUS associated with factor H mutations include the transfusion of fresh-frozen plasma, plasmapheresis, and liver transplantation 1 3 7 14 15 16) .…”

Section: Complement Regulators In Various Diseasesmentioning

confidence: 99%

Complement regulation: physiology and disease relevance

Cho

2015

Korean J Pediatr

The complement system is part of the innate immune response and as such defends against invading pathogens, removes immune complexes and damaged self-cells, aids organ regeneration, confers neuroprotection, and engages with the adaptive immune response via T and B cells. Complement activation can either benefit or harm the host organism; thus, the complement system must maintain a balance between activation on foreign or modified self surfaces and inhibition on intact host cells. Complement regulators are essential for maintaining this balance and are classified as soluble regulators, such as factor H, and membrane-bound regulators. Defective complement regulators can damage the host cell and result in the accumulation of immunological debris. Moreover, defective regulators are associated with several autoimmune diseases such as atypical hemolytic uremic syndrome, dense deposit disease, age-related macular degeneration, and systemic lupus erythematosus. Therefore, understanding the molecular mechanisms by which the complement system is regulated is important for the development of novel therapies for complement-associated diseases.