Chapter 512 Hemolytic-Uremic Syndrome

Hemolytic-uremic syndrome (HUS) is one of the most common causes of community-acquired acute kidney failure in young children. It is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal insufficiency (Table 512-1). HUS has clinical features in common with thrombotic thrombocytopenic purpura (TTP). The etiology and pathophysiology of the more common forms of HUS clearly delineate childhood HUS as separate from idiopathic TTP.

Table 512-1 DEFINITION OF POSTDIARRHEAL HEMOLYTIC UREMIC SYNDROME: CENTERS FOR DISEASE CONTROL AND PREVENTION, 1996

CLINICAL DESCRIPTION

Hemolytic uremic syndrome (HUS) is characterized by the acute onset of microangiopathic hemolytic anemia, renal injury, and a low platelet count. Thrombotic thrombocytopenic purpura (TTP) also is characterized by these features but can include central nervous system (CNS) involvement and fever and can have a more gradual onset. Most cases of HUS (but few cases of TTP) occur after an acute gastrointestinal illness (usually diarrheal).

LABORATORY CRITERIA FOR DIAGNOSIS

The following are both present at some time during the illness:

• Anemia (acute onset) with microangiopathic changes (i.e., schistocytes, burr cells, or helmet cells) on peripheral blood smear and

• Renal injury (acute onset) evidenced by hematuria, proteinuria, or elevated creatinine level: ≥1.0 mg/dL in a child <13 yr or ≥1.5 mg/dL in a patient 13 yr or older or ≥50% increase over baseline.

Note: A low platelet count can usually, but not always, be detected early in the illness, but it can then become normal or even high. If a platelet count obtained within 7 days after onset of the acute gastrointestinal illness is not <150,000/mm³, other diagnoses should be considered.

CASE CLASSIFICATION

Probable

• An acute illness diagnosed as HUS or TTP that meets the laboratory criteria in a patient who does not have a clear history of acute or bloody diarrhea in the preceding 3 wk, or

• An acute illness diagnosed as HUS or TTP that (a) has onset within 3 wk after onset of an acute or bloody diarrhea and (b) meets the laboratory criteria except that microangiopathic changes are not confirmed.

Confirmed

• An acute illness diagnosed as HUS or TTP that both meets the laboratory criteria and began within 3 wk after onset of an episode of acute or bloody diarrhea

COMMENT

Some investigators consider HUS and TTP to be part of a continuum of disease. Therefore, criteria for diagnosing TTP on the basis of CNS involvement and fever are not provided because cases diagnosed clinically as postdiarrheal TTP also should meet the criteria for HUS. These cases are reported as postdiarrheal HUS.

From Elliott EJ, Robins-Browne RM: Hemolytic uremic syndrome, Curr Probl Pediatr Adolesc Health Care 35:305–344, 2005.

Etiology

The various etiologies of HUS allow classification into infection-induced, genetic, medication- induced, and HUS associated with systemic diseases characterized by microvascular injury (Tables 512-2 and 512-3). The most common form of HUS is caused by toxin-producing Escherichia coli that cause prodromal acute enteritis and is commonly termed diarrhea-associated HUS. In the subcontinent of Asia and southern Africa, the shiga toxin of Shigella dysenteriae type 1 is causative, whereas in Western countries verotoxin-producing E. coli (VTEC) are the usual causes.

Table 512-2 CLASSIFICATION OF HEMOLYTIC UREMIC SYNDROME

INFECTION INDUCED

Verotoxin-producing Escherichia coli

Shiga toxin-producing Shigella dysentereriae type 1

Neuraminidase-producing Streptococcus pneumoniae

Human immunodeficiency virus

GENETIC

von Willebrand factor-cleaving protease (ADAMTS 13) deficiency

Complement factor H (or related proteins) deficiency or mutation

Membrane cofactor protein (MCP) mutations

Thrombomodulin mutations

Complement factor I mutations