Oral Presentation Abstract #3197 Rafael Bejar, Kristen E. Stevenson, Petar Stojanov, J. Eric Zaneveld, Michal Bar-Natan, Bennett Caughey, Hui Wang, Guillermo Garcia-Manero, Hagop M. [aamds.org]

Abstract This review summarizes the presentation entitled "Genetic variants in C5 and poor response to eculizumab" (N Engl J Med. 2014; 370: 632-639), given at Symposium 3 entitled "Basic and clinical topics on red blood cell membrane", during the 76th [ncbi.nlm.nih.gov]

={[Rinsho ketsueki] The Japanese journal of clinical hematology}, year={2015}, volume={56 7}, pages={ 855-60 } } Jun-ichi Nishimura Published 2015 in [Rinsho ketsueki] The Japanese journal of… DOI: 10.11406/rinketsu.56.855 This review summarizes the presentation [semanticscholar.org]

They present with clinical features of unexplained hemolytic anemia like fatigue, jaundice and red colored urine. [ijcasereportsandimages.com]

The table below details the published trials presented in the submission. [pbs.gov.au]

• Increased Sweating

  sweating, blotches from small bleeds under the skin and skin redness, hives, muscle spasms, bone pain, back pain, neck pain, swollen joints, kidney damage, painful urination, spontaneous erections, general edema, chest pain, weakness, pain at the infusion [en.wikipedia.org]

• Sweating

  […] and anxiety, a sense of tingling or numbness, blurred vision, vertigo, ringing in the ears, heart palpitations, high blood pressure, low blood pressure, vascular damage, peritonitis, constipation, upset stomach, swollen belly, itchy skin, increased sweating [en.wikipedia.org]

• Blurred Vision

  vision, vertigo, ringing in the ears, heart palpitations, high blood pressure, low blood pressure, vascular damage, peritonitis, constipation, upset stomach, swollen belly, itchy skin, increased sweating, blotches from small bleeds under the skin and [en.wikipedia.org]

• Bone Pain

  pain, back pain, neck pain, swollen joints, kidney damage, painful urination, spontaneous erections, general edema, chest pain, weakness, pain at the infusion site, and elevated transaminases. [6] Pharmacology [ edit ] Eculizumab specifically binds to [en.wikipedia.org]

• Fear

  "One of the reasons for the continued weakness of Alexion's stock this year has been the fear of competition for Soliris in its core complement inhibition indications (PNH, aHUS)," he wrote. [bioworld.com]

• Dark Urine

  This prevents breakdown of red blood cells that occurs in the circulation and turns very dark urine clear almost overnight—in almost all patients. [aamds.org]

  This can lead to low red blood cell counts (anaemia), tiredness, difficulty in functioning, pain, dark urine, kidney failure, shortness of breath and blood clots. [news-medical.net]

• Tingling

  […] pneumonia, upper respiratory tract infection, colds, and urinary tract infection), loss of white blood cells, loss of red blood cells, anaphylactic reaction, hypersensitivity reaction, loss of appetite, mood changes like depression and anxiety, a sense of tingling [en.wikipedia.org]

Workup for connective tissue diseases like ANA, dS-DNA and APLA were done and found to be negative. Bone marrow biopsy was done and revealed hypercellular marrow with no other abnormality. [ijcasereportsandimages.com]

Systematic workup also ruled out HIV infection, antiphospholipid syndrome, and occult infection. Ultrasound showed kidneys of normal size, without thrombosis of renal arteries but with global bilateral hypoperfusion. [journals.lww.com]

The authors concluded that given the complexity of disease pathogenesis in C3G, a patient-tailored approach including a comprehensive workup of complement abnormalities is necessary to evaluate the best treatment options. [aetna.com]

an increase in serum creatinine by 25% or more compared to baseline or nadir during Soliris treatment; or, an increase in serum LDH by 25% or more over baseline or nadir during Soliris treatment. [soliris.net]

Better data on the treatment of acute manifestations of the disease and long term treatment would be required. [pbs.gov.au]

After eculizumab treatment, 80% of plasma-resistant patients required no dialysis treatment. [sjkdt.org]

In 1 patient, sC5b‑9 was elevated and became normal with treatment. However, it was normal before (and throughout) treatment in the other patient. [nice.org.uk]

Soliris typically costs around £340,000 for the first year of treatment of aHUS and £327,000 per year thereafter. According to the Summary of Product Characteristics, treatment is for life. [blog.gfk.com]

Prognosis is poor. Most patients are identified during childhood, and many do not live to adulthood. Currently, there are an estimated 140 to 200 aHUS patients in the UK. [blog.gfk.com]

Annual incidence of aHUS in adults and under the age of 18 are 2/1,000,000 and 3.3/1,000,000, respectively. [4], [5] Frequent relapses are seen in aHUS, and its prognosis is much worse than typical HUS. [6], [7] In 50% of children and in the majority [sjkdt.org]

Conversely patients with mutations in the CFH, CFI, CFB and C3 genes have a much poorer prognosis and for patients with CFH and CFI mutations, a very high chance of recurrence of disease following kidney transplant. [pbs.gov.au]

On admission, a high plasma creatinine level indicated a poor prognosis, and hemodialysis had to be started. [cjasn.asnjournals.org]

Proof of this is that it TMA worsens the prognosis and survival of the patient in all situations in which it complicates the underlying disease: post-partum, kidney transplant and HSCT, MHTN, autoimmune diseases and glomerulopathies. [revistanefrologia.com]

Hetero MTHFR C677T, hetero FVL, and hetero MTHFR A1298C were the most common etiological factors being responsible for 57.1, 42.9, and 42.9% of primary BCS cases, respectively. [worldwidescience.org]

These investigators stated that it would be worthwhile to examine if all cases of immune complex-mediated MPGN without clear underlying etiology should undergo work-up for abnormalities in the alternate complement pathway. [aetna.com]

Birmingham, UK: West Midlands Health Technology Assessment Collaboration, Department of Health and Epidemiology, University of Birmingham; 2008;69:1-67. Madkaikar M, Gupta M, Jijina F, Ghosh K. [aetna.com]

The development of heart failure under complement inhibition and the absence of overt myocardial vascular lesions at postmortem examination suggested an independent pathophysiological process, possibly related to abnormal vasoreactivity. [4] In conclusion [journals.lww.com]

A recent contribution strongly underlined the possibility of recognizing a new mechanism of TA-TMA pathophysiology where the kidney seems the most common organ affected by small vessels injury [ 17 ]. [omicsonline.org]

The pathophysiology of IgA nephropathy. J Am Soc Nephrol, 22 (2011), pp. 1795-1803 [54] J. Rojas-Rivera, G. Fernandez-Juarez, M. Praga. Rapidly progressive IgA nephropathy: a form of vasculitis or a complement-mediated disease. [revistanefrologia.com]

However, the abrogation of intravascular hemolysis is not the only relevant change in PNH pathophysiology associated with eculizumab treatment. [jhoonline.biomedcentral.com]

Recently, there have been new insights into the incidence, pathophysiology, and management of TA-TMA. [aetna.com]

This mutation prevented binding andblockade by eculizumab, thereby explaining the poorresponse to the drug. However, the functional capacityof the mutant C5 to cause haemolysis was retained. [documents.tips]

This prevents breakdown of red blood cells that occurs in the circulation and turns very dark urine clear almost overnight—in almost all patients. [aamds.org]

The increased risk of meningococcal infection seems to be due to the critical action of the terminal complement in prevention of such infections. [austinpublishinggroup.com]

"Independently, though, it binds to leukotriene B4 [LTB4]" as well, which could help in preventing potentially fatal thrombosis among PNH patients. [bioworld.com]