Patients with aHUS are at immediate and ongoing risk for the life-threatening and destructive consequences of complement-mediated TMA1-3
In aHUS, constant, uncontrolled complement activity leads to progressive and life threatening complications1-4
aHUS is a disease associated with chronic risk of complement-mediated thrombotic microangiopathy (TMA) and life-threatening consequences1-4
aHUS is defined as a disease that manifests with1
- The clinical characteristics of TMA (thrombocytopenia, microangiopathic hemolysis, and symptoms of organ dysfunction)
- ADAMTS13 activity >5% (to rule out severe ADAMTS13 deficiency)
- Absence of positive STEC test (to rule out STEC-HUS)
33% - 40% of all patients die or progress to end-stage renal disease with the first clinical manifestation despite plasma exchange or plasma infusion (PE/PI)5,6
Study description: An analysis of the outcomes of 40 patients with the complement factor H (CFH) mutation from the database of the International Registry of Recurrent and Familial HUS/TTP. The cumulative fraction of patients free of events (defined as the combination of the occurrence of chronic renal insufficiency or initiation of dialysis or death, whichever occurred first after the onset of HUS) was estimated by Kaplan-Meier analysis.
* Patients with CFH mutations. CFH mutations = most common population.6
† 94% of these patients received plasma exchange or plasma infusion (PE/PI).6
79% of patients with aHUS die, require dialysis, or have permanent renal damage within 3 years5
Plasma exchange or plasma infusion (PE/PI) as treatment for aHUS has been clinically ineffective1,5-7
Study description: Analysis of patients from the aHUS registry of the GPN (Working Group for Pediatric Nephrology). 141 patients were included in the registry at the time of this analysis. Data on treatment of initial manifestations was available for 99 patients.
* 42% of patients received PE, 48% received PI, and 22 patients received both PE and PI.12
PE/PI is not sufficient to remove mutant complement factors or replace deficient factors2,8-10
- Apheresis procedures themselves may also lead to complement activation11
- Mean plasma levels of complement Ba, a key marker of complement activity, are similarly elevated among patients with aHUS receiving or not receiving plasma exchange or plasma infusion8
Patients with aHUS receiving initial PE/PI have equally poor outcomes after 1 year compared to patients without initial PE/PI12
1. Laurence J. Atypical hemolytic uremic syndrome (aHUS): making the diagnosis. Clin Adv Hematol Oncol. 2012;10(suppl 17):1-12. 2. Legendre CM, Licht C, Muus P, et al. N Engl J Med. 2013;368:2169-2181. 3. Sellier-Leclerc A-L, Frémeaux-Bacchi V, Dragon-Durey MA, et al; French Society of Pediatric Nephrology. Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2007;18:2392-2400. 4. Noris M, Mescia F, Remuzzi G. STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol. 2012;8:622-633. 5. Noris M, Caprioli J, Bresin E, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol. 2010;5:1844-1859. 6. Caprioli J, Noris M, Brioschi S, et al; for the International Registry of Recurrent and Familial HUS/TTP. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006;108:1267-1279. 7. Sarode R, Bandarenko N, Brecher ME, et al. Thrombotic thrombocytopenic purpura: 2012 American Society for Apheresis (ASFA) consensus conference on classification, diagnosis, management, and future research. J Clin Apher. 2013; DOI: 10.1002/jca.21302. [Epub ahead of print]. 8. Cofiell R, Kukreja A, Bedard K, et al. Poster presented at the 55th Annual Meeting of the American Society of Hematology; December 7-10, 2013; New Orleans, LA. Abstract 2184. 9. Waters AM, Licht C. aHUS caused by complement dysregulation: new therapies on the horizon. Pediatr Nephrol. 2011;26:41-57. 10. Heinen S, Pluthero FG, van Eimeren VF, et al. Monitoring and modeling treatment of atypical hemolytic uremic syndrome. Mol Immunol. 2013;54:84-88. 11. Boogaerts MA, Roelant C, Goosens W, et al. Complement activation and adult respiratory distress during intermittent flow apheresis procedures. Transfusion. 1986;26:82-87. 12. Riedl M, Hofer J, Rosales A, et al. Initiale plasmatherapie bei patienten mit atypischem HUS: kein negative Vorhersagewert für das outcome nach einem jahr. Klin Padiatr. 2011; 223-P031 DOI: 10.1055/s-0031-1273832.