Consensus regarding diagnosis and management of atypical hemolytic uremic syndrome

Abstract

Thrombotic microangiopathy (TMA) is defined by specific clinical characteristics, including microangiopathic hemolytic anemia, thrombocytopenia, and pathologic evidence of endothelial cell damage, as well as the resulting ischemic end-organ injuries. A variety of clinical scenarios have features of TMA, including infection, pregnancy, malignancy, autoimmune disease, and medications. These overlapping manifestations hamper differential diagnosis of the underlying pathogenesis, despite recent advances in understanding the mechanisms of several types of TMA syndrome. Atypical hemolytic uremic syndrome (aHUS) is caused by a genetic or acquired defect in regulation of the alternative complement pathway. It is important to consider the possibility of aHUS in all patients who exhibit TMA with triggering conditions because of the incomplete genetic penetrance of aHUS. Therapeutic strategies for aHUS are based on functional restoration of the complement system. Eculizumab, a monoclonal antibody against the terminal complement component 5 inhibitor, yields good outcomes that include prevention of organ damage and premature death. However, there remain unresolved challenges in terms of treatment duration, cost, and infectious complications. A consensus regarding diagnosis and management of TMA syndrome would enhance understanding of the disease and enable treatment decision-making.

Discontinuation of Eculizumab treatment after hematological remission in patients with atypical and drug-induced hemolytic uremic syndrome

“…aHUS is a life-threatening condition; therefore, TPE should be considered standard care until a firm diagnosis is made [7]. When thrombotic thrombocytopenic purpura (TTP), HUS, and secondary thrombotic microangiopathy syndromes have been ruled out, switching to eculizumab treatment is generally recommended [7,9]. Observational studies of patients with aHUS showed that 56%-67% of adults progressed to ESRD within 1 and 3 years, respectively [10,11].…”

“…It can be speculated that removing these autoantibodies from circulation with TPE may be sufficient for achieving hematologic remission. On the other hand, patients with MCP, THBD, or C3 mutations (90%, 62%, and 43%) could be provided with complete remission with TPE alone, according to the literature [6,7,9]. In our study population, two patients had CHF mutations.…”

“…Clinical trials and observational studies showed reduced mortality, and renal recovery and survival increased with eculizumab treatment compared to therapeutic plasma exchange (TPE) [7]. On the other hand, the optimal treatment duration with Eculizumab is not known.…”

Is the COVID‐19 thrombotic catastrophe complement‐connected?

“…Interestingly, although anemia, thrombocytopenia, and particularly elevations in lactate hydrogenase are frequently observed in patients with COVID‐19, fragmentation hemolysis is not a major feature. This does not, however, exclude a diagnosis of complement‐mediated TMA, as even in active aHUS, schistocytes are not always detected on peripheral blood smear examination 65,66 …”

Atypical hemolytic uremic syndrome after childbirth: a case report

“…Atypical HUS is caused by inborn or acquired genetic defects of genes that are associated with regulation of the complement pathway. Atypical HUS is known to be triggered by factors that induce the activation of complement cascades, including infection, pregnancy, organ transplantation, malignancy, autoimmune disease, and drugs (1). Cases of pregnancyassociated atypical HUS are known to occur during the postpartum period (2).…”