Hemolytic Uremic Syndrome (HUS)

Hemolytic uremic syndrome (HUS) facts

• Hemolytic uremic syndrome (HUS) is a condition characterized by destruction of red blood cells and kidney failure.
• HUS often follows a digestive infection caused by E. coli OH157:H7, although there are other causes.
• Symptoms of HUS include vomiting and diarrhea (often bloody), weakness, lethargy, and bruising (purpura). These symptoms are due to a combination of dehydration, anemia and uremia (the inability of the kidneys to clear waste products from the body).
• Diagnosis of HUS is made by a combination of history, physical exam, and abnormal blood tests. There is no one test that makes the diagnosis of hemolytic uremic syndrome.
• Treatment of HUS is supportive with intravenous fluids. Anemia may require blood transfusion and temporary dialysis may be necessary.
• Children tend to recover from HUS, while adults with HUS may fare less well.

What is a "syndrome?"

In medicine, a syndrome defined as is a collection of symptoms (patient complaints), signs (findings on physical examination), and laboratory or imaging findings that tend to group together and be associated with a specific disease or illness.

What is hemolytic uremic syndrome (HUS)?

Hemolytic uremic syndrome (HUS) is a disease of two body systems. Hemolysis describes the destruction of red blood cells. In hemolytic uremic syndrome, blood within capillaries, the smallest blood vessels in the body, begins to clot abnormally. When red blood cells pass through the clogged capillaries, they are sheared apart and broken. (hemo=blood +lysis=destruction). The second failed system, kidney failure (uremia), occurs when urea and other waste products build up in the bloodstream because the kidneys cannot filter and dispose of them. (urea=a waste chemical + emia= in the blood).
HUS is also related to another disease caused by a similar normal clotting process within the capillaries called thrombotic thrombocytic purpura (TTP). Within the medical literature, these two conditions are often considered together. HUS is more widely known, however, because it has been discussed in the press because of its relationship to a special type of E. Coli (Escherichia coli) infection associated with food poisoning.

What causes hemolytic uremic syndrome?

While the cause of HUS has not been established with certainty, researchers believe that an abnormal inflammation reaction is stimulated in the blood stream causing platelets (the parts of the blood that form clots) to sludge in small blood vessels and form blood clots where they are not supposed to. This uses up the platelets and causes a shortage of them in the rest of the body. This abnormal reaction may be caused by a yet unidentified chemical that is produced in blood plasma (the fluid or non-cellular part of the bloodstream).
The triggering events for HUS are varied and include:

• Enterohemorrhagic E. Coli is a type of bacteria that causes bloody diarrhea. E. coli is a very common type of bacteria in the body, and it is only the OH157:H7 type that causes the problem. It can be found in undercooked meat and other foods; and is one of the causes of food recalls and restaurant-related food poisoning outbreaks. This accounts for almost 90% of HUS in children. The 2011 outbreak of HUS in Germany was due to a different type of Shigela toxin-producing E. coli called 0104:H4.
• Pregnancy and the early postpartum (after delivery) time period and the use of birth control pills are the more common associations with HUS.
• Pneumonia caused by the Streptococcus pneumoniae bacteria is another possible precipitating factor. HUS is rare complication of this common infection. Most often, this pneumonia is treated with antibiotics as an outpatient.
• Medications may be also associated with HUS, including some chemotherapy and immunosuppression drugs, birth control pills, ticlopidine (Ticlid, an anti-platelet drug) and quinine [(Quinerva, Quinite]) an anti-platelet drug].
• AIDS may be associated with HUS.

Furthermore, there is an inherited type of HUS due to a gene mutation that affects the blood clotting mechanism.

What are the signs and symptoms of hemolytic uremic syndrome?

In E. coli-related HUS, gastroenteritis occurs with abdominal cramping, vomiting and profuse bloody, watery diarrhea. This may cause significant dehydration, weakness and lethargy, as well as electrolyte imbalances because of the loss of sodium, potassium, and chloride in the vomit and diarrhea. These symptoms may resolve before the onset of anemia and the kidney failure symptoms of HUS.
The anemia and uremia usually present with weakness, lethargy, and sleepiness. Purpura or small areas of bleeding in the skin may be seen because of low platelet counts.

How is hemolytic uremic syndrome diagnosed?

The healthcare provider will have a suspicion of the disease based on the history and physical examination. Abnormal laboratory tests help confirm the diagnosis. They abnormal findings include:

• Hemolytic anemia: the red blood cell count is low and a peripheral blood smear, in which blood is examined under a microscope, will show that the red cells have been damaged and destroyed. This differentiates hemolysis (hemo=blood + lysis=destruction) from anemia caused by decreased production of blood cells in the bone marrow.
• Thrombocytopenia: a low platelet count
• Uremia: Kidney function can be measured by testing the level of waste products in the blood normally filtered by the kidney. Creatinine is a breakdown product of a muscle protein called creatine .When this level rises, it is an indication of kidney failure or uremia.
• Abnormal urine findings: Blood and protein may be found in the urine when normally they are not present.
• Stool cultures: Since E. coli O157:O7 is the most common cause of HUS, attempts are made to culture the bacteria from stool samples. The body usually clears the bacteria from the stool within a week, so a negative test does not exclude the disease. A positive test helps confirm HUS and will be reported to public health authorities to try to determine the source of the infection. In 2011, outbreaks in Europe were traced by public health authorities to tainted sprouts.

One of the distinguishing findings between HUS and TTP is a normal neurologic examination. The brain function is normal in HUS.

What is the treatment for hemolytic uremic syndrome?

HUS in children tends to be self-limiting, and supportive care is often all that is needed. This may include intravenous fluids for rehydration and rebalancing of electrolytes like sodium and potassium, which can be lost with the diarrhea.
Blood transfusions are only used for the most severe cases of anemia in which the hemoglobin falls below 6 or 7 g/dL (depending on age, the normal value is 11-16).
Kidney failure may be managed expectantly (by observation and supportive care), and dialysis is not often required.
Adults with HUS tend to become more ill and need more aggressive therapy than children with the condition. In addition to the supportive care discussed above, plasmapheresis or plasma exchange may be required. Since it is thought there is an abnormal chemical in the plasma stimulating the abnormal clot formation, removing the plasma and replacing it with donor plasma is helpful in treating adult HUS.
Temporary dialysis may be needed while awaiting recovery of the kidneys from the illness.

What is the prognosis of hemolytic uremic syndrome?

HUS in children tends to be self-limiting, and full recovery should be expected.
Adults do less well. Without aggressive therapy like plasmapheresis and dialysis, up to 40% of those affected may die, and 80% may have kidney impairment. With treatment, the death rate falls to 10% or less and kidney impairment to 25%.
Patients with HUS not related to a diarrheal illness have a worse prognosis than those whose illness is due to an E. coli infection.
In those patients with genetically caused HUS, relapsing illness is common as are kidney failure requiring dialysis and death.

How can hemolytic uremic syndrome be prevented?

Most cases of E. coli-related HUS can be prevented by thorough washing and cooking of food products. The vast majority of cases of HUS are caused by poor food handling from the farmer to the wholesaler and grocer. Proper washing and cooking techniques in the kitchen is the key to prevention.

REFERENCE: CDC.gov. Investigation Update: Outbreak of Shiga toxin-producing E. coli O104 (STEC O104:H4) Infections Associated with Travel to Germany.

Medical Author:

Benjamin Wedro, MD, FACEP, FAAEM

Medical Editor:

Melissa Conrad Stöppler, MD