Definition

Hemolytic uremic syndrome (HUS) is primarily a disease of infancy and early childhood. The triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure defines HUS. HUS is the most common cause of acute renal failure in children. It is an uncommon disorder, with multiorgan involvement caused by intravascular platelet aggregation. The most common cause of HUS is from a toxin (Shiga) produced by the Escherichia coli serotype 0157:H7; it follows a prodromal episode of diarrhea that is frequently bloody. HUS occurs most commonly in the summer months and in rural versus urban populations. Thrombotic thrombocytopenic purpura (TTP) and HUS are terms that are used interchangeably to describe essentially the same disease process. They share a classic pentad: microangiopathic hemolytic anemia, consumptive thrombocytopenia, neurologic signs, renal disease and fever. All 5 are present only 40% at any time during an exacerbation of the illness.

Key History

Key Physical Exam

Risk Factors for Hemolytic Uremic Syndrome

Differential Diagnosis

Diagnostic Testing

Text / literature information and recommendations include:

• CBC – Hemoglobin typically < 8 g/dL (microangiopathic hemolytic anemia with fragmented RBCs must have schistocytes), thrombocytopenia (< 60,000/mcL)
• Peripheral smear – Schistocytes, helmet cells
• Coombs test – Negative
• UA – Hematuria, protein, leukocytes
• BUN/Creatinine – Elevated
• LDH – Typically very high
• PT/PTT – Within normal range, differentiating HUS from DIC
• Reticulocyte count – Elevated

Clinical Risk and Safety Pearls

• The diagnosis of HUS should be considered in a patient with a recent history of diarrhea who presents with decreasing urine volume despite being adequately hydrated.
• The diagnosis of HUS should be considered in a patient with a recent history of diarrhea who presents with signs of a multisystem disorder and/or neurological symptoms.
• Antibiotics are not effective except for certain forms caused by Shigella dysenteriae. Antibiotics may increase the risk of developing HUS in children with E coli 0157:H7 colitis. Bactrim may increase verotoxin production by E coli 0157:H7.
• Mortality rate is between 5% and 15%.
• 85% of children with HUS recover after supportive therapy alone.
• Adults with HUS have a poorer prognosis than children. Treat like TTP with plasmapheresis.

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Treatment

Common text / literature recommendations include:

The treatment options for hemolytic uremic syndrome (HUS) vary depending on whether the condition is typical (Shiga toxin-producing Escherichia coli, STEC-HUS) or atypical (aHUS).

Supportive Care:

• Fluid and Electrolyte Management: Critical for all HUS patients to maintain hydration and correct electrolyte imbalances.
• Dialysis: Required in 30%-60% of children with HUS due to acute renal failure. Both peritoneal and hemodialysis are effective.
• Blood Transfusions: May be necessary for severe anemia and thrombocytopenia.

Specific Treatments for STEC-HUS:

• Avoid Antibiotics and Antidiarrheal Agents: Antibiotics can exacerbate the release of Shiga toxin, and antidiarrheal agents can prolong toxin exposure.
• Plasma Exchange or Infusion: Generally not recommended for STEC-HUS as it has not shown significant benefit.

Specific Treatments for aHUS:

• Eculizumab: A humanized monoclonal antibody that inhibits complement protein C5, preventing the formation of the membrane attack complex. It is the first-line treatment for aHUS and has shown significant efficacy in inducing remission and improving renal outcomes.
• Plasma Therapy: Plasma exchange or infusion can be used, especially in cases where eculizumab is not available. Fresh frozen plasma provides complement regulatory proteins like factor H.

Monitoring and Follow-Up:

• Regular Monitoring: Continuous monitoring of renal function, hemoglobin, platelet counts, and complement activity is essential.
• Long-Term Management: For aHUS, long-term eculizumab therapy may be required, and genetic counseling is recommended due to the hereditary nature of complement dysregulation.

Complications