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. HUS 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 and 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 which are used interchangeably to describe essentially the same disease process. The 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 RBC’s 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 cause 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:

• Supportive management with careful management of fluid status directed toward an euvolemic status
• Treatment of blood pressure elevation if present – calcium channel blockers are the initial choice. ACE inhibitors are not recommended because of the concern of reduced renal perfusion although this remains controversial. Some experts feel ACE inhibitors may have a renal protective effect.
• Dialysis for acute renal failure
• Plasmaphoresis may be needed for severe cases (children with significant neurologic symptoms), older children and adults. Plasma Infusion or Exchange:
• Infusion - Presumably adds a substance deficient in TTP patients
• Exchange - allows a large volume of plasma to be administered without volume overload. Also may remove toxic substances in plasma
• Exchange 1-1.5 times the predicted plasma volume with fresh frozen plasma (FFP)
• Plasma exchange may be initiated even if there is uncertainty about the diagnosis.
• Treatment with plasma exchange should be continued until the clinical condition and neurologic manifestations improve, and the platelet count rises.
• In a recent study, patients required an average of 8 treatments, with the replacement of 190 units of FFP.
• If plasma exchange is not immediately available, FFP (30ml/Kg) should be administered.
• A diuretic may be necessary to prevent fluid overload, as large volumes of FFP will be needed.
• Blood transfusion if symptomatic – watch for fluid overload and hyperkalemia.
• Blood transfusion is recommended for hemoglobin level less than 6 g/dL to avoid cardiac and pulmonary compromise. About 80% of patients with HUS require transfusions. Post transfusion goal of 8 to 9 g/dL is recommended. Blood transfusions should be given slowly and cautiously with frequent monitoring of the patient’s vital signs.
• Platelet transfusion if actively bleeding and count less than 50,000 – rare occurrence. This should only be performed in consultation with specialist. May cause life-threatening hemorrhage.
• Consultation with hematologist and nephrologist
• NO antibiotics and NO anti-motility drugs
• Steroids may be of some benefit and should be initiated.

Complications