Eculizumab, a monoclonal antibody directed against the C5 fraction, has been a major advance in the clinical management of this disease, by controlling intravascular haemolysis and thromboembolism4. anaemia due to mechanical damage of red cells, leading to multi-organ damage, particularly in the renal and nervous systems. Both may be associated with infections, autoimmunity, pregnancy, disseminated malignancy, and bone marrow transplantation, and more rarely are congenital. However, HUS is typically characterised by renal impairment (leading to renal failure and requiring dialysis) and is more frequently associated with severe pneumococcal pneumonia, or with Akt3 diarrhoea caused by infection with Shiga-toxin producing O157 (STEC), this last form being characteristic in children. Moreover, HUS is less responsive than TTP to plasma-exchange, whereas it benefits from the recombinant complement inhibitor eculizumab1. TTP is caused by a severe deficiency of ADAMTS13, a plasma metalloprotease that cleaves the most thrombogenic, ultralarge forms of von Willebrand factor. The defect is genetic in 2C3% of cases (hereditary ADAMTS13 defect or Upshaw-Schulman syndrome), whereas it has now been largely demonstrated that acquired ADAMTS13 deficiency is due to autoantibodies, giving the rationale for the plasma-exchange therapy and immunosuppressive treatment used in this disease1. The heterogeneous aetiology of TTP and the consequent different restorative approaches to this condition were well recorded by Rizzo em et al. /em 2, based on a review of the literature, as well as their personal experience. They explained a case secondary to systemic sclerosis, another secondary to cytomegalovirus illness, one happening in pregnancy, and one case that was idiopathic and possibly connected with dietary LY2811376 supplements comprising chitosan, a modulator of the activation and adhesion of platelets. All instances were successfully treated with plasma-exchange, and one with rituximab after suspension of plasma-exchange. The authors underlined that TTP was a fatal condition until the introduction, in 1970, of this procedure, a treatment that functions through the alternative of the deficient protease and/or the removal of anti-ADAMTS13 autoantibodies. Plasma-exchange has already been shown to reduce the mortality rate of TTP from 80C90% to 10C20% and is recommended by the Guidelines of the American Society of Apheresis like a daily treatment to be instituted promptly. The Authors recall that individuals who are refractory to plasma-exchange and relapse are candidates for second-level therapy with splenectomy or immunosuppressant medicines (corticosteroids, cyclophosphamide and cyclosporine), but above all with rituximab, a monoclonal chimeric antibody directed against CD20 (indicated on the surface of B lymphocytes). Rituximab LY2811376 has been successfully used in TTP (roughly 130 published instances), only or in association with plasma-exchange, having a total response in 80C100% of instances, and durable remissions enduring for over a yr and in some cases for more than 4 years. The majority of individuals with TTP received rituximab and plasma-exchange concurrently, and this combined therapy reduced the relapse rate compared with that achieved by plasma-exchange only. Most patients were given the standard dose of the drug (375 mg/m2 weekly for 4 weeks), although some responded to only one or two doses, while others required more long term treatment. Re-treatment was also effective in relapsed instances, so that maintenance treatment every 2 weeks for 1 year has also been suggested for chronic-relapsing TTP. In conclusion, rituximab is an effective restorative option for individuals who do not respond to standard treatment, who encounter multiple relapses, or who cannot undergo plasma exchange3. It is worth commenting the thrombotic microangiopathies such as TTP and HUS share some similarities with other forms of acquired haemolytic anaemia. Paroxysmal nocturnal haemoglobinuria (due to LY2811376 a deficiency of decay accelerating element [DAF] and membrane inhibitor of reactive lysis [MIRL] match inhibitors) is the paradigmatic disease in which intravascular haemolysis and thrombotic phenomena dominate the medical picture. Eculizumab, a monoclonal antibody directed against the C5 LY2811376 portion, has been a major advance in the medical management of this disease, by controlling intravascular haemolysis and thromboembolism4. Eculizumab has also been successfully used in a severe form of chilly agglutinin disease, an autoimmune haemolytic anaemia due to immunoglobulin M-mediated haemagglutination and powerful match activation leading to intravascular haemolysis. Actually, the same drug is effective in HUS, by obstructing the irregular activation LY2811376 of the terminal match pathway and the consequent endothelial damage characteristic of the disease1. As far as respect autoimmune haemolytic anaemia (AIHA), rituximab is definitely reported to be effective in about 80C90% of instances of warm AIHA, both at standard doses of 375 mg/m2 weekly for 4 weeks3 and at lower doses (100 mg.
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