II. Epidemiology

  1. Age: Children ages 1 to 10 years old most commonly affected
    1. Contrast with Thrombotic Thrombocytopenic Purpura which is seen primarily in adults
  2. Incidence: 1-3 per 100,000
  3. Peak timing: June to September in United States

III. Pathophysiology

  1. Shiga-Toxin Producing Escherichia coli in 90% of cases (e.g. 0157:H7, STEC)
    1. See Diarrhea-positive Hemolytic Uremic Syndrome below
    2. Other uncommon causes include Shigella dysenteriae, Streptococcus Pneumoniae, HIV Infection, and Influenza
    3. Proinflammatory factors (IL-8, TNFa)
    4. Prothombotic Changes
      1. Fibrin deposited in renal microvasculature
    5. Verocytotoxin induces endothelial injury
      1. Red Blood Cell destruction
      2. Platelet destruction, consumption, sequestration
      3. Platelet thrombus formation
  2. Classic triad (follows Abdominal Pain and Diarrhea)
    1. Microangiopathic Hemolytic Anemia
    2. Acute Renal Failure
    3. Thrombocytopenia
  3. Predictors of HUS development (3-15% of STEC Diarrhea)
    1. Very young or elderly
    2. Close contact with farm animals
    3. Bloody Diarrhea
    4. Fever
    5. Increased White Blood Cell Count
    6. Increased C-Reactive Protein
    7. Early use of antibiotics in STEC Diarrhea
      1. Results in prolonged intestinal exposure to toxin

IV. Types

  1. Diarrhea-positive Hemolytic Uremic Syndrome
    1. Related to Shiga-toxin producing Escherichia coli
  2. Diarrhea-negative Hemolytic Uremic Syndrome
    1. Sporadic in adults
    2. Consider Thrombotic Thrombocytopenic Purpura

V. Risk Factors

  1. Familial risk (Factor H Deficiency)
  2. Precipitating Infection
    1. Escherichia coli
    2. Streptococcus Pneumoniae
  3. Predisposing Medications
    1. Cyclosporine
    2. Tacrolimus
    3. Radiation Therapy
  4. Predisposing Conditions
    1. Pregnancy
    2. Systemic Lupus Erythematosus
    3. Glomerulonephritis
    4. Cancer
  5. Escherichia coli 0157:H7 (Shiga-Toxin) exposures
    1. Vegetables: Alfalfa/radish sprouts, leaf lettuce
    2. Undercooked Meats: Deer, Ground beef, sausage, deli
    3. Unpasteurized drinks: Apple juice, Milks
    4. Contaminated lakes or municipal water supplies
    5. Petting farm animals

VI. Symptoms (symptomatic in all children)

  1. Follows 3-4 day Incubation Period of E. coli 0157:H7
  2. Diarrhea
    1. Bloody Diarrhea (precedes HUS by 3-14 days)
    2. Non-bloody in some cases
  3. Abdominal cramping
  4. Nausea or Vomiting
  5. Low-grade fever
  6. Petechiae and Purpura are rarely present
    1. Contrast with Thrombotic Thrombocytopenic Purpura

VII. Diagnosis

VIII. Labs

  1. Complete Blood Count with Platelets
    1. Anemia with Hemoglobin 8-9 g/dl due to Hemolysis
    2. Thromboctopenia (Platelet Count <150,000)
    3. Leukocytosis
  2. Peripheral Smear
    1. Hemolysis (Burr cells, helmet cells)
  3. Stool Culture
    1. Escherichia coli 0157:H7 variably positive
    2. May have resolved by the time HUS presents
  4. Renal Function Tests
    1. Blood Urea Nitrogen increased
    2. Serum Creatinine increased
  5. Urinalysis
    1. Hematuria
    2. Proteinuria
  6. Other findings
    1. Increased Lactate Dehydrogenase
    2. Coombs negative
    3. Reticulocyte Count increased
    4. Decreased Haptoglobin

IX. Differential Diagnosis

X. Management

  1. Despite similarity to TTP, treatment is different
  2. Supportive Care
    1. Fluid and Electrolyte management
      1. Hydration prior to HUS decreases Renal Failure
    2. Monitor Hemoglobin, Hematocrit and Platelets
      1. Transfuse Red Blood Cells to keep Hemoglobin >6-7
      2. Platelet Transfusions are controversial
        1. May risk thrombosis
    3. Hemodialysis if Renal Failure occurs
  3. Ineffective or proovcative treatments to avoid
    1. Antibiotics are to be avoided
      1. Worsen complication rate
      2. Increase risk of HUS in STEC Diarrhea
    2. Plasmaphoresis
    3. Anti-thrombotic agents
    4. Corticosteroids
    5. Shiga toxin-binding agents

XI. Complications

  1. Gastrointestinal complications
    1. Rectal Prolapse and colitis (10% of cases)
    2. Intussusception
    3. Pancreatitis
    4. Intestinal perforation
  2. Neurologic complications (10%, higher mortality risk)
    1. Altered Mental Status (e.g. coma)
    2. Cerebrovascular Accident
    3. Seizure Disorder
  3. Renal complications
    1. Chronic Renal Failure (25% risk, 3% risk of ESRD)
    2. Hypertension

XII. Prognosis

  1. Hospital stay: 11 days on average
  2. Survival: 90-95%

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Related Studies

Ontology: Hemolytic-Uremic Syndrome (C0019061)

Definition (MSHCZE) Onemocnění charakterizované hemolýzou v souvislosti s poškozením cévního povrchu – tzv. trombotickou mikroangiopatií, poklesem počtu krevních destiček (trombocytopenií s možnými krvácivými projevy) a akutním selháním ledvin. Vzniká nejčastěji u malých dětí, někdy předchází lehká viróza nebo průjmové onemocnění. U dětí nemoc obvykle sama ustupuje, jen v některých případech může postižení ledvin vyústit do chronické renální insuficience. (cit. Velký lékařský slovník online, 2012 http://lekarske.slovniky.cz/ )
Definition (NCI_CTCAE) A disorder characterized by a form of thrombotic microangiopathy with renal failure, hemolytic anemia, and severe thrombocytopenia.
Definition (NCI) A form of thrombotic microangiopathy with renal failure, hemolytic anemia, and severe thrombocytopenia.
Definition (MSH) A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.
Concepts Disease or Syndrome (T047)
MSH D006463
ICD9 283.11
ICD10 D59.3
SnomedCT 123308008, 111407006
English Gasser Syndrome, Gasser's Syndrome, Gassers Syndrome, HAEMOLYTIC-URAEMIC SYNDROME, HEMOLYTIC-UREMIC SYNDROME, Hemolytic-uremic syndrome, Syndrome, Hemolytic-Uremic, HUS - Haemoly uraemic syndrome, HUS - Haemoly uremic syndrome, Haemolytic-uraemic syndrome, RENAL THROMBOTIC THROMBOCYTOPENIC PURPURA <HEMOLYTIC UREMIC SYNDROME>, Hemolytic-Uremic Syndrome, Haemolytic uraemic syndrome -RETIRED-, hemolytic uremic syndrome (diagnosis), HUS (hemolytic uremic syndrome), hemolytic uremic syndrome, Syndrome hemolytic uremic, HUS, RENAL THROMBOTIC THROMBOCYTOPENIC PURPURA HEMOLYTIC UREMIC SYNDROME, kidney thrombotic thrombocytopenic purpura hemolytic uremic syndrome, kidney ttp, renal ttp, Hemolytic Uremic Syndrome, Hemolytic uremic synd, Hemolytic-Uremic Syndrome [Disease/Finding], hemolytic-uremic syndrome (HUS), gasser syndrome, haemolytic-uraemic syndrome, hemolytic-uremic syndrome, Syndrome haemolytic uraemic, HUS - Haemolytic uraemic syndrome, HUS - Hemolytic uremic syndrome, Haemolytic uraemic syndrome, Hemolytic uremic syndrome, Gasser's syndrome, Hemolytic uremic syndrome (disorder), hemolytic-uremic; syndrome, syndrome; hemolytic-uremic, Hemolytic uremic syndrome, NOS, Haemolytic uraemic syndrome, NOS, Hemolytic uremic syndrome -RETIRED-
Spanish SINDROME HEMOLITICO-UREMICO, Síndrome hemolítico urémico, Síndrome hemolítico-urémico, síndrome urémico - hemolítico, síndrome urémico hemolítico - RETIRADO - (concepto no activo), síndrome urémico hemolítico - RETIRADO -, Síndrome Urémico Hemolítico, SUH, síndrome de Gasser, Síndrome urémico hemolítico, síndrome urémico - hemolítico (trastorno), síndrome urémico hemolítico (trastorno), síndrome urémico hemolítico, Síndrome de Gasser, Síndrome Hemolítico-Urémico
Italian Sindrome uremica emolitica, Sindrome uremico-emolitica, Sindrome di Gasser, Sindrome emolitico-uremica
Dutch hemolytisch-uremisch syndroom, syndroom hemolytisch-uremisch, hemolytisch-uremisch; syndroom, syndroom; hemolytisch-uremisch, hemolytisch uremisch syndroom, Gasser-syndroom, HUS, Hemolytisch-uremisch syndroom, Syndroom, hemolytisch-uremisch
French Syndrome hémolytique-urémique, Syndrome hémolytique urémique, SUH, SHU (Syndrome Hémolytique et Urémique), SYNDROME HEMOLYTIQUE ET UREMIQUE, Syndrome hémolytique et urémique, Syndrome de Gasser
German Syndrom, haemolytisch-uraemisch, haemolytisch-uraemisches Syndrom, HUS, Syndrome haemolytic uraemic, HAEMOLYTISCH URAEMISCHES SYNDROM, Haemolytisch-uraemisches Syndrom, haemolytisches uraemisches Syndrom, Gasser-Syndrom, Hämolytisch-urämisches Syndrom
Swedish Hemolytiskt uremiskt syndrom
Japanese ヨウケツセイニョウドクショウショウコウグン, ガッセル症候群, Gasser症候群, 溶血性尿毒症症候群, 溶血尿毒症症候群, 溶血性尿毒症性症候群, 溶血性尿毒性症候群, 溶血性尿毒症候群
Czech hemolyticko-uremický syndrom, Hemolyticko-uremický syndrom, Gasserův syndrom, HUS
Finnish Hemolyyttis-ureeminen oireyhtymä
Portuguese SINDROME HEMOLITICO UREMICO, Síndrome urémica hemolítica, Síndrome de Gasser, Síndrome Hemolítico-Urêmica
Korean 용혈성-요독성 증후군
Polish Zespół hemolityczno-mocznicowy, Zespół Gassera
Hungarian haemolytikus uraemiás syndroma, Syndroma haemolytikus uraemiás, Haemolytikus-uraemiás syndroma, Haemolyticus uraemiás syndroma, HUS, Haemolyticus-uraemiás tünetegyüttes, haemolyticus uraemiás syndroma
Norwegian HUS, Hemolytisk-uremisk syndrom