Hemolytic-Uremic Syndrome

Chapter: Hemolytic-Uremic Syndrome
McMaster Section Editor(s): Mark Crowther
Section Editor(s) in Interna Szczeklika: Andrzej Hellmann, Bogdan Ochrem
McMaster Author(s): Mark Crowther
Author(s) in Interna Szczeklika: Krystyna Zawilska
Additional Information

Definition, Etiology, PathogenesisTop

Hemolytic-uremic syndrome (HUS) is a very rare severe nonimmune hemolytic anemia caused by thrombotic microangiopathy with thrombocytopenia. The dominant clinical feature is kidney dysfunction. In >90% of cases HUS is caused by verotoxin-producing bacteria: enterohemorrhagic Escherichia coli (EHEC) strains (serotype O157:H7 or O104:H4) or Shigella spp (more frequent in children). Other causes responsible for the development of atypical HUS include hereditary abnormalities in complement proteins, viral infections, and certain drugs.

In patients with atypical HUS, uncontrolled activation of the alternative complement pathway takes place (the majority of patients have inherited mutations of genes coding elements of the pathway).

Clinical Features and Natural HistoryTop

HUS may be preceded by bloody diarrhea, urinary tract infection, or skin infection. Dominant clinical features include hemolytic anemia, thrombocytopenia, and renal failure, which are frequently associated with hypertension and fever. Neurologic symptoms are rare. The course of atypical HUS is markedly more severe than that of the typical syndrome.

DiagnosisTop

Diagnostic Tests

1. Complete blood count: Normocytic anemia, erythroblasts and schistocytes present in peripheral blood smears, reticulocyte count increase, thrombocytopenia.

2. Blood biochemical tests: Elevated serum unconjugated bilirubin and lactate dehydrogenase levels, features of impaired renal function.

3. Urinalysis: Proteinuria, microscopic hematuria.

4. Coagulation parameters: Elevated serum levels of fibrin degradation products, sometimes also elevated D-dimer levels.

5. Serologic studies: Normal or slightly decreased ADAMTS-13 (von Willebrand factor–cleaving protease) levels, negative results of Coombs testing.

Diagnostic Criteria

Diagnosis is based on clinical features.

Differential Diagnosis

Disseminated intravascular coagulation, Evans syndrome, catastrophic antiphospholipid syndrome, bacterial sepsis, thrombotic thrombocytopenic purpura (TTP), atypical HUS due to complement component mutations (Table. Clinical and laboratory features which…).

TreatmentTop

In most patients supportive care, early renal replacement therapy, and packed red blood cell transfusions are necessary. Plasmapheresis is administered in many patients in whom differentiating TTP and HUS is difficult.

PrognosisTop

Mortality rates are up 25%. Chronic kidney disease develops in ~25% of surviving patients.

TablesTop

Table. Clinical and laboratory features which may assist in differentiating among DIC, TTP, HUS, and CAPS

Clinical features

DIC

TTP

HUS

CAPS

CNS manifestations

+/−

++

+/−

++

Renal impairment

+/−

+/−

+++

++

Liver impairment

+/−

+/−

+/−

+

Hypertension

−/+

+/−

Fever

+/−

+/−

−/+

-/+

Hemolysis

+

+++

++

+

Thrombocytopenia

+++

+++

++

++

Coagulopathy

+++

+/-

Adapted from: Allford SL, Hunt BJ, Rose P, Machin SJ; Haemostasis and Thrombosis Task Force, British Committee for Standards in Haematology. Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias. Br J Haematol. 2003 Feb;120(4):556-73.

CAPS, catastrophic antiphospholipid syndrome; CNS, central nervous system; DIC, disseminated intravascular coagulation; HUS, hemolytic-uremic syndrome; TTP, thrombotic thrombocytopenic purpura.

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