Hemolytic uremic syndrome

Last updated: November 18, 2022

Summarytoggle arrow icon

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 a 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 article.

Epidemiologytoggle arrow icon

Mainly children < 5 years of age [1]

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Approx. 15% of children infected with E. coli O157:H7 will go on to develop HUS.

Pathophysiologytoggle arrow icon

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. [4]

  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. Damaged endothelial cells secrete cytokines that promote vasoconstriction and platelet microthrombus formation at the site of damage (intravascular coagulopathy) thrombocytopenia (consumption of platelets)
  5. RBCs are mechanically destroyed as they pass through the platelet microthrombi occluding small blood vessels (i.e., arterioles, capillaries) → hemolysis (schistocytes), and end-organ ischemia and damage, especially in the kidneys decreased glomerular filtration rate (GFR)

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

Clinical featurestoggle arrow icon

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:

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

Diagnosticstoggle arrow icon

Differential diagnosestoggle arrow icon

Differential diagnosis of platelet disorders
HUS TTP Disseminated intravascular coagulation (DIC) Immune thrombocytopenic purpura (ITP) Bernard-Soulier syndrome Glanzmann thrombasthenia
Typical presentation
  • Patient with a history of serious underlying illness (e.g., sepsis, trauma, malignancy)
  • Presents with thrombosis, embolism, organ dysfunction, and/or bleeding
Peripheral smear
PT (INR) and aPTT
  • Normal/increased
  • Increased
  • Normal
D-dimer, fibrin degradation products
  • Normal/increased
  • Increased
  • Normal

Other platelet disorders

The differential diagnoses listed here are not exhaustive.

Treatmenttoggle arrow icon

Post-diarrheal HUS is a nationally notifiable condition. [7]

Platelet transfusions should be administered with caution unless patients are bleeding or require an invasive procedure. Some studies suggest that they can exacerbate microangiopathy.

Complicationstoggle arrow icon

HUS can result in microthrombus formation and complications in various organs:

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

Prognosistoggle arrow icon

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.

Referencestoggle arrow icon

  1. Pundzienė B, Dobilienė D, Čerkauskienė R, et al. Long-term follow-up of children with typical hemolytic uremic syndrome. Medicina. 2015; 51 (3): p.146-151.doi: 10.1016/j.medici.2015.06.004 . | Open in Read by QxMD
  2. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw-Hill Education ; 2015
  3. Jokiranta TS. HUS and atypical HUS. Blood. 2017; 129 (21): p.2847-2856.doi: 10.1182/blood-2016-11-709865 . | Open in Read by QxMD
  4. Zoja C, Buelli S, Morigi M. Shiga toxin-associated hemolytic uremic syndrome: pathophysiology of endothelial dysfunction. Pediatr Nephrol. 2010; 25 (11): p.2231-2240.doi: 10.1007/s00467-010-1522-1 . | Open in Read by QxMD
  5. Walsh PR, Johnson S. Eculizumab in the treatment of Shiga toxin haemolytic uraemic syndrome.. Pediatr Nephrol. 2019; 34 (9): p.1485-1492.doi: 10.1007/s00467-018-4025-0 . | Open in Read by QxMD
  6. Pape L, Hartmann H, Bange FC, Suerbaum S, Bueltmann E, Ahlenstiel-Grunow T. Eculizumab in Typical Hemolytic Uremic Syndrome (HUS) With Neurological Involvement.. Medicine. 2015; 94 (24): p.e1000.doi: 10.1097/MD.0000000000001000 . | Open in Read by QxMD
  7. 2017 Nationally Notifiable Conditions. Updated: January 1, 2017. Accessed: March 22, 2017.
  8. Siegler RL, Pavia AT, Christofferson RD, Milligan MK. A 20-year population-based study of postdiarrheal hemolytic uremic syndrome in Utah.. Pediatrics. 1994; 94 (1): p.35-40.
  9. Fitzpatrick MM, Shah V, Trompeter RS, Dillon MJ, Barratt TM. Long term renal outcome of childhood haemolytic uraemic syndrome.. BMJ. 1991; 303 (6801): p.489-492.doi: 10.1136/bmj.303.6801.489 . | Open in Read by QxMD
  10. Atypical Hemolytic Uremic Syndrome. . Accessed: December 11, 2020.

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