Atypical hemolytic uremic syndrome: from diagnosis to treatment

Abstract

Thrombotic microangiopathy (TMA) is a relatively rare condition but a medical urgency requiring immediate intervention to avoid irreversible organ damage or death. Symptoms on presentation include microangiopathic haemolytic anaemia, thrombocytopenia and organ damage. The most frequent direct causes of TMA are thrombotic thrombocytopenic purpura (TTP) and haemolytic uremic syndrome (HUS). The most common form of HUS is related to Shiga toxin producing Escherichia coli (STEC) infection while approximately 10% of cases are due to dysregulation of the complement pathway (atypical haemolytic uremic syndrome, aHUS). Optimal treatment regimens differ depending on the underlying cause; however, differential diagnosis may be difficult. The most accurate method of diagnosis is based on exclusion and should consider, beyond the symptoms common to TMA, ADAMTS13 activity levels and STEC infection status. For the management of TTP, plasma exchange (PE) is the most important acute intervention and is associated with lower mortality and better outcomes than plasma infusion. In most patients with STEC-HUS, the course of disease is selflimiting although management of acute kidney injury is often required. Until recently, the management of aHUS consisted of early and intensive PE, although this was mostly ineffective in protecting from subsequent organ damage. Eculizumab, an inhibitor of the alternative complement pathway, produces a rapid and sustained inhibition of the TMA process, with significant improvements in long-term clinical outcomes. Due to the significant improvement achieved, eculizumab has subsequently been approved as first-line therapy when an unequivocal diagnosis of aHUS has been made.

Thrombotic Microangiopathy in a Patient Treated with Gemcitabine

“…1,3,6 Common infectious agents that cause secondary HUS include Shiga-toxin-producing Escherichia coli, which presents with a bloody diarrhea, HIV, and Streptococcus pneumoniae. 3,5,[7][8][9] The most common drugs related to secondary HUS are quinine, 1,3 gemcitabine, 1 mitomycin C, 9 and cyclosporine. 3 Pregnancy and autoimmune disorders causing HUS have also been reported, but they are rare.…”

Phenocopies: Mimics of Inborn Errors of Immunity

“…The incidence of this pathology is very low, it is estimated 1 -2 cases per mil-lion population, there is no predominance of age. The prognosis is bad and a quarter of the patients develop kidney disease after the onset of the disease, they will also have ischemic symptoms in the CNS, cardiovascular and respiratory system, skin manifestations, skeletal muscle and in the gastrointestinal tract [100]. The diagnosis of a-UHS requires the following findings: 1) microangiopathic hemolytic anemia (hemoglobin < 10 g/dl) with direct negative Coombs test, elevation of lactate dehydrogenase (DHL), decrease of serum haptoglobin with peripheral blood schistocytes, 2) thrombocytopenia (<150,000 cell/mm 3 ), 3) acute kidney injury [101].…”

Változások az őssejt-transzplantációhoz társult thromboticus microangiopathia diagnosztikus kritériumrendszerében

“…A pentád a TTP-s esetek 40%-ában, az első há-rom tünet 70-80%-ban mutatható ki. A TTP diagnózisa kimondható a más okkal nem magyarázható thrombocytopenia és a fragmentocytás haemolyticus anaemia igazolása esetén [5,6]. A HUS jellemző klinikai triádja a consumptiós thrombocytopenia, a microangiopathiás haemolyticus anaemia és az igazolt akut vesekárosodás (proteinuria, glomerularis haematuria, beszűkült vesefunkció, oligo-anuria, emelkedett retenciós értékek) [7].…”

“…A 2000-es évek végén, az atípusos HUS és a TTP etiológiájának tisztázásában a komplementdiagnosztika, valamint az ADAMTS13 (von Willebrand-faktort hasító proteáz) enzimaktivitás és inhibitor meghatározása alapvető vizsgálóeljárássá vált [5,21]. Ugyanakkor, az őssejt-transzplantációhoz társult TMA diagnosztikájára kialakí-tott, fent bemutatott négy kritériumrendszer csak a klinikai paramétereken alapult.…”