Hemolytic uremic syndrome (HUS) is a disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. It is most commonly caused by infections from Shiga toxin-producing bacteria like E. coli O157:H7. The Shiga toxin damages endothelial cells and causes blood clots to form in the kidneys. Treatment involves fluid replacement, dialysis, and plasma exchange to support kidney function and replace lost blood cells. While HUS prognosis is generally good, some children may have long term kidney damage or rarely die from severe complications.

1. HEMOLYTIC UREMIC SYNDROME
JINU JANET VARGHESE
GROUP: 4
YEAR: 5
TBILISI STATE MEDICAL UNIVERSITY

2. DEFINITION
• Hemolytic uremic syndrome (HUS), a disease that destroys red blood cells, is the most common cause
of sudden, short-term acute kidney failure in children.
• It is a triad of:
• Micro-angiopathic hemolytic anemia
• Thrombocytopenia.
• Acute kidney injury (acute renal failure)

3. EPIDEMOLOGY
• Hemolytic uremic syndrome (HUS) is a rare disorder with an annual incidence of 6.1 cases per 100,000
children aged under 5 years (compared with an overall incidence of 1 to 2 cases per 100,000).
• Over 90% of cases in children are secondary to infection. Approximately 15% of cases of E. coli O157
infection will develop HUS. The development of HUS may occur up to two weeks after the initial onset
of symptoms, and may develop after apparent recovery from the initial acute illness. Cases may be
sporadic or occur as part of larger outbreaks. The largest documented outbreak in England occurred in
Cumbria in 1999, and was associated with pasteurized milk.
• About 10% of HUS cases are atypical and are not caused by Shiga toxin-producing bacteria or
streptococci.

4. TYPES OF HUS
Classified into 2 main categories, depending on whether it is associated with Shiga-like toxin or not.
1. TYPICAL HUS:
• Typical HUS follows a diarrheal infection often caused by E. coli OH157:H7. Infection related Shiga toxin
producing E.coli/Shigella Pneumococcal infection HIV Typical Other viral or bacterial infections. Only the
diarrheal form of HUS is considered to be typical HUS and is usually a disease of infants and children
younger than 3 years of age
2. ATYPICAL HUS
• caused by exposure to certain medications (eg ciclosporin, tacrolimus), genetic mutations in the
complement pathway[4] and systemic conditions, including lupus, cancer and pregnancy.

5. PATHOGENESIS
• Specifically, E coli serotype O157:H7 has been associated with more than 80% of infections leading to
Hemolytic Uremic Syndrome.
• The shiga-like toxin affects endothelial cells and initiates intravascular thrombo-genesis. After entering
the circulation via the gastrointestinal mucosa, the toxin preferentially localizes to the kidneys,
inhibiting protein synthesis and eventually leading to cell necrosis or apoptosis.
• Endothelial cell damage subsequently potentiates renal microvascular thrombosis by promoting
activation of the blood coagulation cascade.
• Platelet aggregation results in a consumptive thrombocytopenia. Microangiopathic hemolytic anemia
results from mechanical damage to red blood cells circulating through partially occluded
microcirculation.

6. CAUSES
Hemolytic-uremic syndrome (HUS) predominantly occurs in infants and children after prodromal diarrhea.
In summer epidemics, the disease may be related to infectious causes.
 BACTERIAL INFECTIONS :
• S dysenteriae
• E coli
• Salmonella typhi
• Campylobacter jejuni
• Yersinia pseudotuberculosis
• Neisseria meningitidis
• S pneumoniae
• Legionella pneumophila
• Mycoplasma species

8.  VIRAL INFECTIONS :
• Human immunodeficiency virus (HIV)
• Coxsackievirus
• Echovirus
• Influenza virus
• Epstein-Barr virus
• Herpes simplex virus
 OTHER CAUSES:
• Fungal infections, Vaccinations, Pregnancy, Quinine, Oral contraception, Cancers, Chemotherapeutic
agents, Antiplatelet agents, Collagen-vascular disorder, Primary glomerulopathies, etc.

9. SIGNS & SYMPTOMS
HUS develops about 5-10 days after onset of diarrhea
 EARLY SYMPTOMS:
• Blood in the stools
• Irritability
• Fever
• Lethargy
• Vomiting and diarrhea
• Weakness

10.  LATER SYMPTOMS:
• Bruising
• Decreased consciousness
• Low urine output
• No urine output
• Pallor
• Seizures -- rare
• Skin rash that looks like fine red spots (petechiae)
• Yellow skin (jaundice)

11. DIAGNOSIS
• Findings of hemolysis and thrombocytopenia on a complete blood count are required to establish the
diagnosis.
• Anemia: invariable finding and usually severe
• Thrombocytopenia: Platelet survival time is shortened in HUS.
• The peripheral blood smear reveals fragmented RBCs (e.g., schistocytes, spherocytes, segmented RBCs)
• Reticulocytosis (proportional to hemolysis) and circulating free hemoglobin may be found
• Increased serum thrombo-modulin levels may be found and are a marker for endothelial injury in HUS.
• Leukocytosis: moderate leukocytosis in post diarrheal cases indicates renal failure due epithelial injury
• disseminated intravascular coagulopathy (elevated fibrin split products, prolongation of the activated
partial thromboplastin time, and low anti-thrombin III levels)

12. Healthy red blood cells (left) are smooth and round. In hemolytic uremic
syndrome, toxins destroy red blood cells (right). These misshapen cells may clog
the tiny blood vessels in the kidneys.

13. Schistocytes as seen in a person with hemolytic-uremic syndrome

14. A bloody diarrhea is followed in a few days by renal failure caused by endothelial
injury from the toxin, leading to the characteristic fibrin thrombi in glomerular
and interstitial capillaries.

15. • Because of intravascular hemolysis, direct bilirubin values are elevated with elevated serum lactate
dehydrogenase (LDH) level
• Renal function and electrolytes: a rise in urea and creatinine may be due to dehydration
• Azotemia
• Elevated C-reactive protein level
• Negative Coombs’ test
• Stool culture positive for Shiga toxin–roducing Escherichia coli O157:H7
• Hematuria on urinalysis

16. COMPLICATIONS
GASTROINTESTINAL NEUROLOGIC RENAL
• Intestinal
strictures/perforations
• Intussusception
• Pancreatitis
• Severe colitis
• Altered mental status
• Focal neurologic signs
• Seizures
• Chronic renal failure
• Hematuria
• Hypertension
• Proteinuria

17. DIFFERNTIAL DIAGNOSIS
• Acute abdomen
• Acute gastroenteritis
• Appendicitis
• Colitis
• Disseminated intravascular coagulation
• Inflammatory bowel disease
• Lupus
• Thrombotic thrombocytopenia

18. TREATMENT & MANAGEMENT
• Hemolytic uremic syndrome requires treatment in the hospital. To ease immediate signs and symptoms and
prevent further problems, hemolytic uremic syndrome treatment may include:
• FLUID REPLACEMENT: The key treatment for HUS is fluid replacement. This treatment replaces electrolytes
that the body needs to function. Fluid replacement also increases blood flow through the kidneys. The extra
fluids help offset the impaired blood flow that occurs due to the breakdown of red blood cells.
• KIDNEY DIALYSIS
• PLASMA EXCHANGE
• PLATELET TRANSFUSIONS
• RED BLOOD CELL TRANSFUSIONS: Low RBCs result in chills, fatigue, short of breath, rapid heart rate, yellow
skin and dark urine. Transfusions (IV) can relieve these symptoms.

19. • Antibiotics and antimotility agents are not recommended as treatments for hemolytic uremic syndrome
during the diarrheal stage of the disease. Some children who were diagnosed with Shigella dysenteriae type
1 and treated with ampicillin developed hemolytic uremic syndrome.
• Use of monoclonal antibodies which block complement activity. Case reports of experimental treatments
with eculizumab is used to treat congenital atypical hemolytic uremic syndrome, as well as severe shiga-toxin
associated hemolytic uremic syndrome.
• These have shown promising results. Eculizumab was approved by the U.S. Food and Drug Administration
on September 23, 2011 for the treatment of atypical hemolytic uremic syndrome (aHUS) It was approved by
the European Medicines Agency on November 29, 2011 for the treatment of aHUS.
• Trials of gamma globulin are under way, with promising preliminary results. Findings suggest the possibility
of some benefit in children.
• Azathioprine and vincristine are potent drugs with potential benefit in the management of HUS.

20. PROGNOSIS
• Typical hemolytic uremic syndrome (HUS) with a diarrheal prodrome usually has a good prognosis. The
two British Pediatric Surveillance Unit prospective surveys in the UK and Ireland (1985-1988 and 1997-
2001) of HUS in children under 16 years reported a mortality rate of HUS in the first of these surveys to
be 5.6% and this had decreased to 1.8% in the second survey.
• Death due to HUS is nearly always associated with severe extra-renal disease, including severe central
nervous system involvement.
• Fatality is highest in infants, small children and the elderly.
• Whilst renal recovery is the norm, there have been permanent and serious renal sequelae
(hypertension, proteinuria, diminishing glomerular filtration rate) found in 5-25% of HUS patients.
• Atypical HUS often has a poorer prognosis, with death rates reportedly as high as 25%, and progression
to end-stage renal disease in 50%.

21. PREVENTION
• The organism is very common in cattle and a low level of infection causes clinical disease. Prevention is
based on reducing fecal contamination during slaughtering and processing.
• Good personal hygiene measures, e.g. hand-washing before and after food-handling and eating, after
toilet use and after contact with farm animals.
• Increased public awareness about good food hygiene, eg cook meat and meat products well, especially
where minced or in burger form; avoid cross-contamination between raw and cooked food.
• Early diagnosis enables early supportive treatment and better ultimate prognosis. Similarly, early
identification of an outbreak enables public health measures to be put in place to prevent further cases.
Separating known cases from their younger siblings may also be an appropriate measure.
• Conjugate vaccines against E. coli O157 are in development - phase 3 trials are awaited.

22. REFERENCES
• http://emedicine.medscape.com/article/1183555-treatment
• http://www.patient.co.uk/doctor/Haemolytic-Uraemic-Syndrome.htm
• http://www.healthline.com/health/hemolytic-uremic-syndrome
• https://www.clinicalkey.com/topics/hematology/hemolytic-uremic-syndrome.html
• http://en.wikipedia.org/wiki/Hemolytic-uremic_syndrome#Treatment
• http://www.mayoclinic.org/diseases-conditions/hemolytic-uremic-syndrome/basics/treatment/con-
20029487
• http://www.aafp.org/afp/2006/0915/p991.html