HEMOLYTIC

UREMIC
SYNDROME
ANKIT GURJAR
 • When Gasser et al. first described hemolytic uremic
syndrome (HUS) in 1955, it was usually a fatal illness. HUS
mainly appeared in early childhood and included the
combination of Coombs-negative (nonimmune)
thrombocytopenic microangiopathic hemolytic anemia
and irreversible acute renal failure.
• HUS accounts for 7% of cases of hypertension in infants
younger than 12 months.
• Hemolytic uremic syndrome (HUS) is a clinical syndrome
characterized with the triad of microangiopathy hemolytic
INTRODUCTION anemia, thrombocytopenia and acute renal damage.
• It is one of the most common pathology behind acute
renal damage in children. The clinical findings in hemolytic
uremic syndrome is occur due to thrombotic
microangiopathy (TMA).
• Escherichia Coli (STEC) producing Shiga-toxin (Stx) is the
most common cause of of HUS, called as STEC-HUS. In the
childhood, complement-related HUS constitutes the
majority of HUS cases other than STEC-HUS.
STEC-HUS is usually start within a few days after
clinical gastroenteritis caused by STEC (usually
serotype O157:H7 or O104:H4), and the Shiga toxin is
main in causing endothelial cell damage, thereby
initiating the disease process.
Understanding the main differences the pathogenesis
of aHUS and STEC-HUS began with the discovery of
the association between aHUS and mutations in the
gene coding for the key complement factor H (CFH).
Thereafter, mutations in several other complement
INTRODUCTION
regulators and other complement proteins, such as
C3, factor B, factor I, and CD46, have been also
identified.

Many patients have more than 1 mutation or rare

polymorphisms affecting the complement system.
hemolytic uremic syndrome mainly has two types
 EPIDEMIOLOGY
• 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 2-3 cases per 100,000).
• STEC-HUS is responsible of 90% of childhood HUS cases. the lowest rate adults
aged 50-59 years (0.5 cases per 100,000 per year).D+ HUS mortality less than
10% , adults poorer prognosis. D- HUS, overall mortality rate approaches 26%
About 10% of HUS cases are atypical and are not caused by Shiga toxin-
producing bacteria or streptococci.
• Over 90% of cases in children are secondary to infection. It is observed more
commonly in summer months and rural areas.
• The most common serotype responsible of the disease is E.coli O157:H7,
Approximately 15% of cases of E. coli O157 infection will develop HUS.
• it can be sporadic or occur as part of larger outbreaks.
EPIDEMIOLOGY
• The largest documented outbreak in England
occurred in Cumbria in 1999, and was
associated with pasteurized milk. On the other
hand, the great EHEC outbreak which affected
Germany and 15 European countries in 2011
occured because of E. coli O104:H4 serotype.
In this outbreak, a total of 3842 people were
affected, HUS were developed in 845 and 52
mortality were reported.
• In Australia, an outbreak occur which is
responsible for hemorrhagic colitis and HUS
with E. coli O111 serotype . but there are less
commonly Cases of HUS have also been
reported with different serotypes (O26, O145,
O103) . in India, Bangladesh and South Africa
Shigella dysenteria Type 1 is responsible of a
small portion of STEC-HUS cases. It causes to
a more severe disease picture and the risk of
progression to chronic renal disease is higher.
 • 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 ).
PATHOPHYSIOLOGY 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 circulation →
toxin-mediated endothelial injury → microthrombus formation →
blockage of small vessels → RBC fragmentation (hemolysis) and end-
organ damage
bloody diarrhea, weakness
and lethargy ,irritability,
fever.

Later, more symptoms may

CLINICAL
appear, such as: PRESENTATION

Pale skin, Unexplained bruising or bleeding,

Swelling of the face, hands, feet or any other part
of the body, pallor, Seizures (these are rare)
Decreased consciousness, Decreased urination,
Low urine output, No urination, Skin rash that
looks like fine red spots (petechiae), Yellow skin
(jaundice), enteritis, hyperglycemia.
DIAGNOSTIC TEST
• we will perform a physical exam and ask about history.
perform some lab work, including blood and urine tests.
These tests will look for signs of anemia and kidney
failure.
• Blood cultures are negative in E coli –mediated disease
since only the shiga-like toxin is circulating in the blood
while the organisms remain in the GI lumen.
• Stool cultures typically detect shiga toxin-producing E
coli. More advanced tests include a stool culture or a
kidney biopsy.
• hemoglobin level typically less than 8 g/dL, which can
be seen in cbc. Schistocytes are seen in a person with
hemolytic-uremic syndrome. peripheral smear Blood
film – schistiocytes,burr cells, helmet cell, spherocytes
and segmented rbc, Thrombocytopenia platelet counts
of less than 60,000 per mL. but no purpura nor active
bleeding ,LDH level elevated.
TREATMENT
• Treatment of hemolytic uremic syndrome requires a hospital
stay. the patient has to be hydrated by giving Intravenous
(IV) fluids. due to kidney failure hypertension can occur and it
can be controlled by medication like nifedipine, labetalol,
nitroprusside.
• Dialysis may be needed to keep the blood clean if the kidney
failure is severe. Antibiotics are not needed to treat the
diarrhea. The infection will resolve on its own. With proper
care, patients with the disease can recover without permanent
damage to their health. children recover more fasten then
adults.
• The key treatment for HUS is fluid replacement. To ease
immediate signs and symptoms and prevent further problems,
hemolytic uremic syndrome treatment may include fluid
resuscitation, plasmapheresis performed if anuria found,
insulin therapy to correct hyperglycemia and ketone bodies.
 TREATMENT
• 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. eculizumab
monoclonal anti- C5 antibody that interrupts complement system.
• in severe cases of bleeding if plasma exchange can not be performed
immediately then blood transfusion can be performed. Low RBCs result
in chills, fatigue, short of breath, rapid heart rate, yellow skin and dark
urine. Transfusions (IV) can relieve these symptoms.
• avoid antimotility agent because there is a risk of tocix megacolon.
platelate transufusion avoided because it can leads to thrombosis, renal
failure and death but in life threatning condition it can be uses under
supervision of hematologist.
• Some children who were diagnosed with Shigella dysenteriae type 1 and
treated with ampicillin developed hemolytic uremic syndrome.
 CONCLUSION
• HUS mainly appeared in early childhood amd adult patient. adults vs
children In adults females more affected more frequent severe neurological
abnormalities, more severe thrombocytopenia and anemia. triad include
the combination of Coombs-negative (nonimmune) thrombocytopenic
microangiopathic hemolytic anemia and irreversible acute renal failure.
Hemolytic uremic syndrome often begins with vomiting and diarrhea, which
may be bloody. Call your doctor immediately if you or your child have
bloody diarrhea plus decreased urine output, unexplained bruises, unusual
bleeding, or extreme fatigue. your doctor will perform some lab work,
including blood and urine tests. More advanced tests include a stool culture
or a kidney biopsy. These tests will look for signs of anemia and kidney
failure. Treatment of HUS is supportive care with intravenous fluids. Anemia
may require blood transfusion and dialysis may be necessary to help treat
kidney failure. Good sanitation and maintenance of food hygiene can
prevent diarrhea associated HUS. it is anticipated that future research in
hus will results in more precise diagnostic method to identify disease earlier.
REFERENCE

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523989/
• https://www.aafp.org/afp/2006/0915/p991.html?
fbclid=IwAR30cMpNsVRxd63mifzYTYcBntMFDkqWIniIcniHod6h1qL6PIrD2svL
QtA#abstract
• https://emedicine.medscape.com/article/1183555-followup
• http://medind.nic.in/ibv/t09/i12/ibvt09i12p1075.pdf