Hemolytic-uremic syndrome (HUS) is an acute, fulminant disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury. HUS usually occurs in children following an infection, typically with Shiga toxin–producing bacteria (eg, Escherichia coli O157:H7
(See also Overview of Platelet Disorders.)
Pathophysiology of HUS
Hemolytic-uremic syndrome, like thrombotic thrombocytopenic purpura (TTP), involves nonimmunologic platelet destruction. Endothelial damage is common. Loose strands of platelets and fibrin are deposited in multiple small vessels and damage passing platelets and red blood cells (RBCs), causing significant thrombocytopenia and anemia (microangiopathic hemolytic anemia). Platelets are also consumed within multiple small thrombi, contributing to the thrombocytopenia.
vasculitis. Large-vessel thrombi are uncommon.
Etiology of HUS
Most cases occur in children and follow
Acute infection
Most often (about 90% of cases), the infection is acute hemorrhagic colitis resulting from Shiga toxin–producing bacteria (eg, Escherichia coli O157:H7, or some strains of Shigella dysenteriae). Occasionally, the cause is pneumococcal infection or rarely HIV infection.
A small minority of cases are unrelated to infection and involve
Dysregulation of the complement system
Complement dysregulation is usually from a mutation in genes controlling complement proteins or factors but sometimes from acquired autoantibodies to certain complement factors. Congenital complement disorders may also increase the risk of hemolytic-uremic sydrome (HUS) following infection.
Symptoms and Signs of HUS
Children with Shiga toxin-related hemolytic-uremic sydrome (HUS) usually have a prodrome of vomiting, abdominal pain, and diarrhea (frequently bloody) and often a history of exposure to infection. Patients with pneumococcal-related HUS usually have manifestations of pneumonia, meningitis, or sepsis. Fever does not usually occur. About a week after the prodrome, manifestations of hemolytic anemia, thrombocytopenia, and acute kidney injury develop. Complement-mediated HUS does not usually have an infectious prodrome.
Manifestations of ischemia develop with varying severity in multiple organs. Neurologic manifestations occur in about one quarter of patients and include weakness, confusion, and seizures. Kidney injury may produce hematuria, decreased urination or anuria, and/or hypertension. Despite thrombocytopenia, purpura and overt bleeding are uncommon although gastrointestinal tract ischemia may cause significant hemorrhagic colitis, with abdominal pain, nausea, vomiting, and bloody diarrhea. Cardiac involvement may cause arrhythmias.
Diagnosis of HUS
Complete blood count (CBC) with platelets, peripheral blood smear, direct antiglobulin (Coombs) test, LDH, PT, PTT, fibrinogen
Exclusion of other thrombocytopenic disorders
thrombotic thrombocytopenic purpura
The diagnosis is suggested by
Thrombocytopenia and anemia
Fragmented red blood cells on the blood smear indicative of microangiopathic hemolysis (schistocytes: helmet cells, triangular RBCs, distorted-appearing RBCs)
Evidence of hemolysis (falling hemoglobin level, polychromasia, elevated reticulocyte count, elevated serum LDH and bilirubin, reduced haptoglobin)
Negative direct antiglobulin test
By permission of the publisher. From Tefferi A, Li C. In Atlas of Clinical Hematology. Edited by JO Armitage. Philadelphia, Current Medicine, 2004.
Diagnosis of cause
Stool testing (Shiga toxin enzyme-linked immunosorbent assay or specific culture media for E. coli O157:H7) is done in children with diarrhea and also adults who had a prodrome of bloody diarrhea; however, the organism and toxin may have cleared by the time of presentation.
In atypical cases, that is, in patients who have not had preceding infection or who have recurrent disease, testing for complement factor gene mutations is recommended.
Treatment of HUS
Supportive care, often including hemodialysis
Typical diarrhea-associated hemolytic-uremic syndrome in children caused by enterohemorrhagic infection usually spontaneously remits and is treated with supportive care; antibiotics are not used. Over half of patients require renal dialysis. Unlike with thrombotic thrombocytopenic purpura, plasma exchange and corticosteroids are not used.
Key Points
Platelets and red blood cells are destroyed nonimmunologically, leading to thrombocytopenia and anemia; renal failure is common in children and adults with hemolytic-uremic syndrome (HUS).
Cause in children is typically hemorrhagic colitis resulting from Shiga toxin–producing bacteria.
Less common causes involve complement dysregulation from a variety of inherited and acquired causes
Typical diarrhea-associated hemolytic-uremic syndrome in children usually spontaneously remits with supportive care, although over half of affected children require renal dialysis.
