Haemolytic Uraemic Syndrome

Haemolytic uraemic syndrome is a serious condition that damages small blood vessels, most commonly affecting the kidneys and often occurring after bacterial infection, particularly in young children.

Table of contents

• What is haemolytic uraemic syndrome?
• Types of haemolytic uraemic syndrome
• What causes haemolytic uraemic syndrome?
• Who gets haemolytic uraemic syndrome?
• Signs and symptoms
• How is haemolytic uraemic syndrome diagnosed?
• Treatment options
• Possible complications
• Prevention
• Outlook and recovery

What is haemolytic uraemic syndrome?

Haemolytic uraemic syndrome, also called HUS, is a condition that happens when small blood vessels throughout the body become damaged and inflamed^[1]. This damage causes blood clots to form in these tiny vessels. The clots can seriously affect how organs work, especially the kidneys^[1].

HUS is a type of thrombotic microangiopathy, which means it involves damage to small blood vessels that leads to clotting^[3]. The condition is characterized by three main problems: destruction of red blood cells (called hemolytic anemia), low levels of platelets in the blood (called thrombocytopenia), and damage to the kidneys leading to acute kidney injury^[3].

When red blood cells pass through damaged blood vessels, they get broken apart. The kidneys contain tiny filtering units called glomeruli, and when these become clogged with damaged red blood cells and blood clots, the kidneys cannot do their job of filtering waste from the blood^[20].

Types of haemolytic uraemic syndrome

There are several different types of haemolytic uraemic syndrome, each with different causes^[2]:

• Typical haemolytic uraemic syndrome (also called Shiga toxin-producing E. coli HUS or STEC HUS): This is the most common type. It develops after infection with certain bacteria, especially strains of E. coli that produce a toxin^[2].
• Atypical haemolytic uraemic syndrome (aHUS): This rare type is usually caused by inherited genetic problems that affect how the body’s immune system works^[2]. It occurs in less than 1 person in 1 million people^[12].
• Secondary haemolytic uraemic syndrome: This type occurs alongside other medical conditions^[2].

In atypical HUS, biological parents can pass genetic mutations down to their children. An illness, infection, or environmental factor can then trigger these genetic changes to become active^[12].

What causes haemolytic uraemic syndrome?

Most cases of HUS are caused by infection with certain strains of Escherichia coli (E. coli) bacteria^[1]. The most common strain is called E. coli O157:H7^[5]. These bacteria produce a harmful substance called Shiga toxin, which damages blood vessels^[5].

People usually become infected with these bacteria by eating contaminated food, such as undercooked meat, or by drinking unpasteurized milk or juice^[8]. The infection can also spread through contact with cattle or other farm animals, or from person to person if hygiene is not maintained^[8].

Other causes of HUS include^[1][5]:

• Other bacteria such as Shigella, Salmonella, or Streptococcus pneumoniae
• Certain medications, including some used for chemotherapy
• Pregnancy and the postpartum period
• Cancer
• Autoimmune diseases
• Genetic mutations affecting the immune system’s complement pathway

The bacteria release their toxin in the intestines, which is why many people first develop diarrhea, often bloody^[8]. The toxin then enters the bloodstream and damages the lining of small blood vessels throughout the body^[3].

Who gets haemolytic uraemic syndrome?

Anyone can develop haemolytic uraemic syndrome, but it is most common in young children, especially those under 5 years of age^[1][6]. About 8 in 10 children with HUS have an infection with Shiga toxin-producing E. coli^[6].

Among people who develop diarrhea from E. coli infection, between 5% and 15% will go on to develop HUS^[2]. The condition affects approximately 1.5 per 100,000 people per year^[5].

Young children are at higher risk, but adults can also develop HUS, and they may experience more complicated symptoms^[5]. People who are immunocompromised or who have existing kidney, urinary, or lower digestive tract problems may also be at increased risk^[15].

Signs and symptoms

The symptoms of haemolytic uraemic syndrome can vary depending on what caused it^[1]. When HUS is caused by E. coli bacteria, the first symptoms are related to the intestinal infection and typically include^[1][2]:

• Diarrhea, which is often bloody
• Pain, cramping, or bloating in the stomach area
• Fever
• Vomiting
• Nausea

After a few days of diarrhea, HUS may develop. At this stage, symptoms result from damage to blood vessels and include^[1][2]:

• Loss of color in the skin (pale appearance)
• Extreme tiredness and weakness
• Easy bruising or unexplained bruising
• Tiny red spots on the skin
• Unusual bleeding, such as from the nose and mouth
• Decreased urinating or not urinating at all
• Blood in the urine
• Swelling (edema) of the legs, feet, ankles, or face
• Headache
• Confusion or decreased alertness
• Seizures
• Rapid heart rate

In severe cases, damaged red blood cells cause blood clots that can damage organs beyond the kidneys, including the heart and brain^[2]. When the kidneys are affected and cannot filter waste properly, this leads to increased toxin levels in the blood, high blood pressure, and shortness of breath^[2].

If someone with diarrhea shows signs of HUS, such as urinating less often, losing pink color in the cheeks and inside the lower eyelids, or developing unexplained bruises, they should seek emergency medical care immediately^[6]. HUS is a medical emergency^[6].

How is haemolytic uraemic syndrome diagnosed?

A physical exam and laboratory tests can confirm a diagnosis of haemolytic uraemic syndrome^[9]. Healthcare providers will typically start by taking a thorough medical history, including asking about recent diarrhea, fever, or contact with potentially contaminated food or animals.

Several laboratory tests are used to diagnose HUS^[9][16]:

• Blood tests: These can show if red blood cells are damaged, reveal low platelet counts, show low red blood cell counts, or detect higher than normal levels of creatinine (a waste product that the kidneys normally remove)
• Urine test: This can find unusual levels of protein and blood in the urine, and signs of infection
• Stool sample: This test can identify E. coli and other bacteria in the stool

If the cause of HUS is not clear, additional tests may be needed. For atypical HUS, genetic testing may be performed to identify specific genetic mutations^[17].

There is no single laboratory test for HUS. Instead, doctors look for the combination of three key findings: destruction of red blood cells, low platelet count, and decreased kidney function^[8]. The diagnosis is made based on clinical symptoms and laboratory results together^[8].

Treatment options

Haemolytic uraemic syndrome requires treatment in the hospital^[9]. The main approach is supportive care, which means helping the body recover while managing symptoms^[11].

For typical HUS caused by Shiga toxin-producing bacteria, treatment focuses on^[11]:

• Replacing lost fluids and minerals through intravenous (IV) fluids
• Providing nutrition, sometimes through a vein
• Blood transfusions to replace damaged red blood cells and help reverse anemia
• Careful monitoring of kidney function
• Dialysis if the kidneys stop working properly

Antibiotics are generally not recommended for typical HUS caused by E. coli, because they can actually make symptoms worse by causing the bacteria to release more toxin^[11]. Platelet transfusions are usually avoided unless there is active bleeding^[10].

For atypical HUS, treatment may include^[9][11]:

• Plasma exchange (also called plasmapheresis): A procedure that removes and replaces blood plasma to eliminate harmful substances
• Complement inhibitor medications: Two drugs, eculizumab (Soliris) and ravulizumab (Ultomiris), are approved specifically for treating atypical HUS. These medications work by blocking part of the immune system that causes blood vessel damage
• Medications to control high blood pressure

Anyone taking eculizumab or ravulizumab must receive a vaccination to prevent meningitis, which is a possible serious side effect of these medicines^[9].

In cases where HUS leads to permanent kidney failure, kidney transplantation may be necessary^[11]. Kidney transplantation is safe and effective for children who progress to end-stage kidney disease, with a recurrence rate of HUS after transplant of only 0-10%^[11].

Possible complications

HUS can lead to serious health problems and can affect multiple organs in the body^[1][5]. The most common complications involve the kidneys, but other organs can be affected as well.

Kidney-related complications include:

• Acute kidney failure requiring dialysis (occurs in approximately half of children with typical HUS)^[15]
• Long-term kidney problems
• Chronic kidney disease
• Permanent kidney failure in some cases

Other possible complications include^[1][5]:

• Neurological problems such as confusion, seizures, or stroke
• Heart problems including heart failure
• High blood pressure
• Liver damage
• Brain damage

Less than 25% of people with HUS develop long-term kidney problems after recovery^[1]. However, without proper treatment, severe cases of HUS can be life-threatening. The risk of death is less than 5% when treated in developed countries^[1][5].

People who have had HUS need regular medical follow-ups to monitor kidney function and watch for any long-term complications^[11].

Prevention

Preventing infection with E. coli and other bacteria that can cause HUS is the key to preventing the disease^[8]. The following measures can help prevent infection^[8]:

• Never eat rare or undercooked ground beef. Cook ground beef to an internal temperature of 160°F (71°C)
• Keep raw meat separate from ready-to-eat foods
• Wash hands, counters, utensils, and plates after contact with raw meat
• Always refrigerate meat products and never leave raw meats at room temperature
• Do not drink milk, milk products, fruit juices, or ciders that have not been pasteurized
• Always wash raw fruits and vegetables before eating
• Make sure children wash their hands carefully, especially after using the toilet and after touching or handling animals, particularly farm animals
• Always wash hands with soap and water before and after preparing foods and after using the toilet or changing diapers
• Do not use public swimming facilities while having diarrhea
• Clean and disinfect diapering areas, toilets, potty chairs, and toys at least daily and when soiled
• Stay home when you have diarrhea

Adequate hydration is important to minimize kidney damage in HUS associated with Shiga toxin-producing E. coli infections^[15]. It is also advised to avoid antibiotics, medications that slow intestinal movement, and non-steroidal anti-inflammatory drugs when E. coli infection is suspected^[15].

Outlook and recovery

Treating haemolytic uraemic syndrome in time leads to a full recovery for most people, especially young children^[1]. Most people with HUS recover within a few weeks with appropriate hospital care and supportive treatment^[6].

The outlook depends on several factors including the type of HUS, how quickly treatment begins, and the severity of organ damage. Children generally have better outcomes than adults^[5].

For typical HUS caused by E. coli infection, most children recover completely if treated quickly and properly, with their kidney function returning to normal^[8]. However, some may develop permanent health problems, particularly related to kidney function.

Atypical HUS may have a more complicated course. People with atypical HUS may develop a chronic (long-lasting or recurring) form of the condition^[6]. They can also experience more severe symptoms and chronic health problems, including high blood pressure, kidney failure, and blood clots throughout the body^[6].

With modern treatments, particularly complement inhibitor medications for atypical HUS, outcomes have improved significantly^[10]. Regular monitoring and follow-up care are essential for all people who have had HUS to watch for any late complications or recurrence of the disease.