Hemolytic Uremic Syndrome in Emergency Medicine Treatment & Management

Updated: Jun 24, 2021
  • Author: Audrey J Tan, DO; Chief Editor: Steven C Dronen, MD, FAAEM  more...
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Treatment

Emergency Department Care

Emergency department (ED) care for patients with hemolytic uremic syndrome (HUS) should focus on supportive management, correction of blood pressure elevation, blood transfusions, and if necessary, arrangement for prompt dialysis.

Avoid unnecessary use of antibiotics or antimotility agents during diarrheal illness. The use of these agents has been shown to increase the incidence of HUS because as motility slows, the gut is exposed to the toxins for a longer period of time. Additionally, antibiotic-induced injury to the bacterial membrane favors the acute release of large amounts of toxins. Use of antibiotics has been shown to increase the risk of full-blown HUS by 17-fold, and thus, the recommendation is to avoid its use, except in cases of sepsis.

Maintain fluid balance. In light of the diarrheal illness, fluid resuscitation is important, although one must avoid fluid overload. Watch for and treat hyperkalemia. If indicated, treat acute kidney injury aggressively with hemodialysis.

A study of children with HUS from Shiga toxin–producing Escherichia coli (STEC-HUS) found that fluid infusion soon after diagnosis led to a significantly better short-term outcome, with a lower rate of central nervous system involvement (7.9% vs 23.7%, P = 0.06), less need for renal replacement therapy (26.3% vs 57.9%, P = 0.01) or intensive care support (2.0 vs. 8.5 days, P = 0.02), and fewer days of hospitalization (9.0 vs 12.0 days, P = 0.03). Long-term outcomes were also significantly better in terms of renal and extrarenal sequelae (13.2% vs 39.5%, P = 0.01). [12]

Treat hypertension with standard antihypertensive agents.

Plasma exchange (plasmapheresis combined with fresh-frozen plasma replacement) is currently the treatment of choice. Plasma exchange is performed daily until remission is obtained. However, because 85% of children with hemolytic uremic syndrome recover after supportive therapy alone, plasma exchange is generally reserved for the most severe cases.

The U.S. Food and Drug Administration (FDA) has approved two monoclonal antibodies for the treatment of atypical HUS (aHUS): eculizumab and ravulizumab. These monoclonal antibodies inhibit complement-mediated thrombotic microangiopathy. Both of these agents carry black box warnings regarding meningococcal infection, which include a recommendation to immunize patients with meningococcal vaccines at least 2 weeks before starting treatment. [13, 14]

Eculizumab

Eculizumab (Soliris) is the first treatment approved by the US Food and Drug Administration (FDA) (September, 2011) for adults and children with atypical hemolytic uremic syndrome (aHUS). Approval was based on data from adults and children who were resistant or intolerant to, or receiving, long-term plasma exchange/infusion. Data also included children (aged 2 mo to 17 y) who received eculizumab with or without prior plasma exchange/infusion. Eculizumab demonstrated significant improvement in platelet count from baseline (P = 0.0001). Thrombotic microangiopathy events were reduced, and maintained or improved kidney function was also reported. [13, 15, 16]

Treatment with eculizumab consists of weekly infusions in the initial phase (up to 4 weeks) followed by eculizumab infusions every 14–21 days depending on the body weight of the patient, potentially their entire life. However, there are no studies that provide strong evidence in favor of lifelong treatment with eculizumab. This, together with the high cost of eculizumab, has caused a debate regarding duration of treatment. [11]

In a study of 11 children (median age 22 months, range 11-175) with enterohemorrhagic E coli–positive HUS requiring dialysis, Pape and colleagues reported that early use of eculizumab appears to improve neurological outcome. All the study patients had seizures and/or were in a stupor or coma. Three patients died and of the surviving 8 patients, none experienced further seizures after the first dose of eculizumab. Three patients showed mild neurological impairment at discharge, while the remaining 5 showed no impairment. [17]

Optimal duration of eculizumab therapy is not yet known. Because of the potential risk of developing TMA following discontinuation of treatment, lifelong treatment has been suggested.  Menne and colleagues confirmed the efficacy and safety of eculizumab with a long-term observational study over 6 years of 93 patients from 0-80 years old who participated in eculizumab trials and received at least one eculizumab infusion. Among the 42 patients that discontinued eculizumab, 50% (21) patients reinstated therapy.  Discontinuation of eculizumab was associated with higher risk of TMA and decreases in renal function. Patients at highest risk for TMA following discontinuation included those with pediatric disease onset, identified genetic or autoimmune complement abnormalities, and a history of multiple TMAs. [18]  

Ravulizumab

Ravulizumab (Ultomiris) was approved by the FDA in 2019 for the treatment of aHUS in adult and pediatric patients aged 1 month and older. Like eculizumab, ravlizumab is a monoclonal antibody that inhibits complement-mediated thrombotic microangiopathy (TMA) [14]  

Approved was based on data from 2 ongoing single-arm open-label studies that evaluated the efficacy of ravulizumab in pediatric (n=13) and adult (n=56) patients with aHUS. The studies demonstrated a complete TMA response in 71% of children and 54% of adults during the initial 26-week treatment period, as evidenced by normalization of hematological parameters (platelet count and LDH level) and ≥25% improvement in serum creatinine from baseline. Additionally, ravulizumab treatment resulted in reduced thrombocytopenia in 93% of children and 84% of adults; reduced hemolysis in 86% of children and 77% of adults; and improved kidney function in 79% of children and 59% of adults. [19]   

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Consultations

Consult a hematologist and a nephrologist to help manage the case and an intensivist to admit the patient to an ICU setting, if necessary. In severe cases, consider consulting the renal transplant service if renal dysfunction persists.

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