• Clinical science

Hemolytic uremic syndrome

Abstract

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy in which microthrombi, consisting primarily of platelets, form and occlude the arterioles and capillaries. These occlusions result in the simultaneous occurrence of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). HUS predominantly affects children and is caused by bacterial toxins, most commonly the Shiga-like toxin of enterohemorrhagic Escherichia coli (E. coli) O157:H7. If there is strong suspicion of HUS based on clinical presentation and initial laboratory tests, treatment should begin immediately, as the condition may result in renal failure. Patients receive symptomatic treatment for renal symptoms, anemia, and complications affecting other organs, such as the brain and GI tract.

Thrombotic thrombocytopenic purpura (TTP), the other main type of thrombotic angiopathy, is discussed in the respective learning card.

Epidemiology

  • Mainly children < 5 years of age

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Approx. 15% of children infected with E. coli O157:H7 will go on to develop HUS!
References:[2][1]

Pathophysiology

HUS is a thrombotic microangiopathy, a condition characterized by the formation of microthrombi occluding the microvasculature. The other main thrombotic microangiopathy is thrombotic thrombocytopenic purpura (TTP). The two conditions have some pathophysiology and clinical findings in common, but different etiologies. HUS is caused by bacterial toxins.

  1. Infection with enterohemorrhagic E. coli (EHEC) or another causative organism
  2. Mucosal inflammation facilitates bacterial toxins entering systemic circulation.
  3. Toxins cause endothelial cell damage (especially in the glomerulus ).
  4. Endothelial cell dysfunction: Damaged endothelial cells; secrete cytokines that promote vasoconstriction and platelet microthrombus formation at the site of damage (intravascular coagulopathy).
  5. The glomerular filtration rate (GFR) decreases and RBCs are mechanically destroyed as they pass through the platelet microthrombi occluding small blood vessels (i.e., arterioles, capillaries) → hemolysis and end-organ ischemia and damage, especially in the kidneys

E. coli O157:H7 infection → Shiga-like toxin in systemic circulationtoxin-mediated endothelial injury → microthrombus formation → blockage of small vessels → RBC fragmentation (hemolysis) and end-organ damage
References:[3][4]

Clinical features

A diarrheal illness (usually bloody) for the past 5–10 days precedes the onset of HUS symptoms in many children. The triad of clinical findings occurring in HUS consists of: :

  1. Low platelets (i.e., thrombocytopenia)
  2. Microangiopathic hemolytic anemia
  3. Impaired renal function

The typical HUS patient is a preschooler who has had a diarrheal illness for the last 5–10 days and presents with petechiae, jaundice, and oliguria!


References:[2][5]

Diagnostics

References:[6][5][7]

Differential diagnoses

Differential diagnosis of platelet disorders
HUS TTP Disseminated intravascular coagulation (DIC) Immune thrombocytopenic purpura (ITP) Bernard-Soulier syndrome Glanzmann thrombasthenia
Pathophysiology
  • ADAMTS13 deficiency
  • Systemic coagulation activation
  • Platelet and coagulation factor consumption (mixed disorder)
Subjective state of patient
  • Patient unwell
  • Patient unwell
  • Patient unwell
  • Patient well
  • Patient well
  • Patient well
Typical presentation
  • Previously healthy adult, sometimes associated with triggers (e.g., infection, surgery, pregnancy)
  • Presents with mental status changes, fever, petechiae, fatigue, and pallor
  • Patient with a history of serious underlying illness (e.g., sepsis, trauma, malignancy)
  • Presents with thrombosis, embolism, organ dysfunction, and/or bleeding
Peripheral smear
  • Normal, Platelets
  • Abnormal results on platelet aggregation testing confirm the diagnosis.
PT (INR) and aPTT ↔/↑ ↔/↑ ↑↑
D-Dimer, fibrin degradation products

↔/↑

↔/↑ ↑↑

Other platelet disorders

References:[8][9][10][11][12][13][14]

The differential diagnoses listed here are not exhaustive.

Treatment

  • Avoid antibiotics and antimotility agents
  • Monitor and correct
    • Fluid status abnormalities
    • Electrolyte disturbances
    • Acid-base abnormalities
    • Blood pressure
    • RBC transfusions
  • Dialysis as indicated for AKI: Up to 50% of HUS patients require dialysis.
  • Only in refractory cases: plasma exchange therapy
  • Eculizumab : approved by the FDA for use in aHUS, may also be beneficial in HUS with neurological symptoms
  • Antiepileptic drugs (e.g., diazepam, phenytoin): indicated in patients with seizures
  • Post-diarrheal HUS is a nationally notifiable condition.

Platelet transfusions should be administered with caution unless patients are bleeding or require an invasive procedure. Some studies suggest that they can exacerbate microangiopathy!
References:[2][15][16][17][18]

Complications

HUS can result in microthrombus formation and complications in various organs

References:[5]

We list the most important complications. The selection is not exhaustive.

Prognosis

The prognosis depends primarily on prompt initiation of treatment. Timely treatment can prevent acute complications (AKI, coma, and death) as well as progression to chronic renal failure.

  • With treatment, the mortality rate of HUS is low: < 5%
  • Long-term renal sequelae occur in 5–25% of children with HUS .
  • Atypical HUS has a less favorable prognosis and higher likelihood of progressing to end-stage renal disease.

References:[2][17][19]